Clinical trials
Welcome to the Amyloidosis Clinical Trials page!
This page is designed to be easy to understand for both patients and clinicians alike.
Clinical trials are subdivided into major amyloidosis types: ATTR, AL and Other.
Please SCROLL DOWN for full details.
Clinical trials are listed here once the first health service in Australia has fully opened the trial for patient enrollment.
Once a trial has been listed as being open (or “activated“) at one site, other sites in Australia selected to participate will also be listed, even thought they may not yet be fully open (“pending“).
Please note : Listing a clinical trial on this website does not necessarily equate as endorsement of the trial by the Australian Amyloidosis Network. Any patient interested in a trial should discuss the pros and cons of the studies with their treating practitioner.
For each trial, a description of the trial, including key inclusion and exclusion criteria, and local contacts are provided.
The trial status at each site will be indicated by a symbol.
The key is as follows:
Systemic Light Chain Amyloidosis (AL) trials
Newly diagnosed:
AFFIRM-AL (NEOD001-301): A Phase 3 Randomized, MultI-Centre Double-Blind, Placebo-Controlled, Efficacy and Safety Study of Birtamimab Plus Standard of Care vs Placebo Plus Standard of Care in Newly Diagnosed Mayo Stage IV Subjects with Light Chain AL Amyloidosis
What is the drug in question?
Birtamimab – this is a monoclonal antibody that attaches to the amyloid deposits and hopefully this promotes your own immune system to clear the amyloid deposits in your body. This is combined with the typical standard treatment, usually “VCD” chemotherapy.
Who is eligible for the trial?
Newly diagnosed patients with systemic AL amyloidosis with advanced disease in the heart.
Does every patient receive the actual trial drug?
Two out of every three patients will receive birtamimab and one out of three will receive a placebo (“dummy”) drug. Neither you nor your treating team will know which drug you are on.
How is the drug administered?
Birtamimab is given through an IV (drip into the vein) every 28 days
How long does the trial go for?
Once 135 patients have received at least 9 months of treatment, the data will be analysed, and a decision of whether to stop the trial or continue will be made then.
Anything else I need to know?
This trial has been previously performed in patients with newly diagnosed AL amyloidosis but only those with advanced heart disease appeared to possibly benefit. This current trial called “AFFIRM” is looking to see whether a benefit can be proven in more advanced heart disease when a larger number of patients are analysed.rres.
Key inclusion criteria:
- Newly diagnosed, treatment naive systemic AL amyloidosis with:
- Bone marrow demonstrating clonal plasma cells
- Confirmed diagnosis of AL amyloidosis by the following:
- Histochemical diagnosis of amyloidosis determined by polarizing light microscopy of green birefringent material in Congo red-stained tissue specimens OR characteristic electron microscopy appearance AND
- Confirmatory immunohistochemistry OR mass spectroscopy of AL amyloidosis
- Cardiac involvement as defined by all of the following:
- Past documented or presently noted clinical signs and symptoms supportive of a diagnosis of heart failure due to amyloidosis in the absence of an alternative explanation for heart failure
- Either an endomyocardial biopsy demonstrating AL amyloidosis OR an echocardiogram demonstrating a mean left ventricular wall thickness at diastole >12 mm in the absence of other causes (e.g., severe hypertension, aortic stenosis), which would adequately explain the degree of wall thickening
- Confirmed Mayo Stage IV as defined by:
- NT-proBNP ≥1800 pg/mL and
- Troponin-T >0.03 ng/mL and
- dFLC ≥18 mg/dL
- Planned first-line chemotherapy contains bortezomib administered subcutaneously weekly
- Adequate bone marrow reserve, hepatic function, and renal function, as demonstrated by:
- Absolute neutrophil count ≥1.0 × 109/L
- Platelet count ≥75 × 109/L
- Hemoglobin ≥9 g/dL
- Total bilirubin ≤ 2 × the upper limit of normal (ULN)
- Aspartate aminotransferase (AST)≤3 × ULN
- Alanine aminotransferase (ALT) ≤3 × ULN
- Alkaline phosphatase (ALP) ≤5 × ULN
- Estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2
- Seated systolic blood pressure (BP) 90 to 180 mmHg
- Distance walked during Screening 6MWT is >30 meters and <550 meters
Key exclusion criteria:
Subjects must meet none of the following criteria:
- Non-AL amyloidosis
- NT-proBNP >8500 pg/mL
- Meets the International Myeloma Working Group (IMWG) definition of multiple myeloma (Appendix 3)
*Note that subjects who meet the IMWG definition of symptomatic multiple myeloma with signs and/or symptoms attributable only to associated amyloidosis are potentially eligible upon approval of the Sponsor. - Subject is eligible for and plans to undergo ASCT or organ transplant during the study
- Symptomatic orthostatic hypotension that in the medical judgment of the Investigator would interfere with the subject’s ability to safely receive treatment or complete study assessments
- Myocardial infarction, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or ECG evidence of acute ischemia, within 6 months prior to the Month 1- Day 1 Visit
- Severe valvular stenosis (e.g., aortic or mitral stenosis with a valve area <1.0 cm2) or severe congenital heart disease
- ECG evidence of acute ischemia or active conduction system abnormalities with the exception of any of the following:
- First degree A V-block
- Second degree AV-block Type 1 (Mobitz Type 1 / Wenckebach type)
- Right or left bundle branch block
- Atrial fibrillation with a controlled ventricular rate (uncontrolled [>110 bpm] ventricular rate is not allowed [determined by an average of 3 beats in Lead II or 3 representative beats if Lead II is not representative of the overall ECG])
- Peripheral neuropathy assessed as National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade 2 with pain, Grade 3, or Grade 4
- Subject is receiving oral or intravenous antibiotics, antifungals, or antivirals within 1 week of Month 1-Day 1 with the exception of prophylactic oral agents
- Prior treatment with hematopoietic growth factors, transfusions of blood or blood products within 1 week of Month 1-Day 1
- Prior radiotherapy within 4 weeks of Month 1-Day 1
- Major surgery within 4 weeks of Month 1-Day 1 or planned major surgery during the study
- Active malignancy with the exception of any of the following:
- Adequately treated basal cell carcinoma, squamous cell carcinoma, or in situ cervical cancer
- Adequately treated Stage I cancer from which the subject is currently in remission and has been in remission for 2 years
- Low-risk prostate cancer with Gleason score <7 and prostate-specific antigen <10 ng/mL
- Any other cancer from which the subject has been disease-free for ≥2 years
- History of severe allergy to any of the components of birtamimab such as histidine/L histidine hydrochloride monohydrate, trehalose dehydrate, or polysorbate 20 or history of Grade ≥3 infusion-related AEs or hypersensitivity to another monoclonal antibody, or known hypersensitivity to diphenhydramine (or an equivalent H1 antihistamine) or acetaminophen (or its equivalent, paracetamol)
- Prior treatment with plasma cell-directed chemotherapy, birtamimab, daratumumab, 11-1F4, anti-serum amyloid P antibody, doxycycline for amyloid, or other investigational treatment directed at amyloid
- History of epilepsy or seizure disorder with the exception of childhood febrile seizures
- Waldenström’s macroglobulinemia and/or immunoglobulin M monoclonal gammopathy
For more information, please contact one of the five recruiting centres in
Australia, or use this link.
Sites
New South Wales
| Status: | |
| Site: | St George Hospital, Sydney |
| Contact: | Principal Investigator: Dr. Shir-Jing Ho Study Co-ordinator: Lindy Williams lindy.williams@health.nsw.gov.au ph: 02 9113 4831 |
Victoria
| Status: | |
| Site: | Eastern Health, Melbourne |
| Contact: | Principal Investigator: Dr. Olga Motorna Study Co-ordinator: Liz Arnold liz.arnold@monash.edu ph: 03 9094 9503 |
Queensland
| Status: | |
| Site: | ICON Cancer Center South Brisbane |
| Contact: | Principal Investigator: Prof. Kerry Taylor Study Co-ordinator: Tara Thompson tara.thompson@icon.team Ph: 07 3737 4501 |
Western Australia
| Status: | |
| Site: | Royal Perth Hospital |
| Contact: | Principal Investigator: Prof. Michael Leahy Study Co-ordinator: Monika Stoeska Monika.Stoeska@health.wa.gov.au Ph: 08 9224 1533 |
South Australia
| Status: | |
| Site: | Royal Adelaide Hospital |
| Contact: | Principal Investigator: Dr. Noemi Horvath Study Co-ordinator: Rino Amato rino.amato@sa.gov.au Ph: 08 7074 5719 |
Relapsed/refractory:
A Study to Assess Change in Disease Activity and Adverse Events (AE)s in Adult Participants With Immunoglobulin Light Chain (AL) Amyloidosis Receiving ABBV-383 as an Intravenous (IV) Infusion
Study Summary
ABBV-383: Immunoglobulin light chain (AL) amyloidosis is the most common form of systemic amyloidosis. AL amyloidosis has many root causes and is characterized by the overproduction of AL that are secreted by clonal bone marrow plasma cells. This is a study to determine adverse events and change in disease activity in adult participants with AL amyloidosis treated with ABBV-383.
ABBV-383 is an investigational drug being developed for the treatment of AL amyloidosis. This study in broken into 2 parts (dose escalation and safety expansion) with 5 arms. During dose escalation (arms 1-3) participants will receive 1 of 3 doses of ABBV-383 to determine the part 2 doses. After completion of the dose escalation portion of the study, the safety expansion (part 2) portion of the study will begin. Two arms (arm 4-5) will begin and participants will receive 1 of 2 doses as determined during the dose escalation portion (part 1). Around 76 adult participants with relapsed/refractory AL amyloidosis will be enrolled at approximately 20 sites across the world.
Participants will receive ABBV-383 as an infusion into the vein for up to approximately 2 year study duration.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and questionnaires.
Who is eligible for the trial?
Patients with relapsed or refractory systemic AL amyloidosis who have previously been treated with bortezomib and daratumumab.
Does every patient receive the actual trial drug?
All patients receive ABBV-383.
How is the drug administered?
After an initial dose step up phase ABBV-383 is given as a subcutaneous injection every 28 days.
How long does the trial go for?
The treatment continues for 2 years in an estimated 76 patients. The trial will continue to watch the response in patients for a number of years after the treatment finished.
Key inclusion criteria:
- Diagnosis of primary systemic immunoglobulin light chain (AL) amyloidosis.
- Eastern Cooperative Oncology Group (ECOG) performance status of <= 2.
- Have at least 1 organ historically impacted by AL amyloidosis.
- Considered AL amyloidosis risk stage 1, 2, or 3a and have measurable disease of AL amyloidosis as defined by difference between involved and uninvolved free light chains (dFLC) >= 50 mg/L.
- Has previously been exposed to a proteasome inhibitor (PI) and an anti-CD38 monoclonal antibody.
Key exclusion criteria:
Subjects must meet none of the following criteria:
- Known history of clinically significant (per investigator’s judgment) drug or alcohol abuse within the last 6 months.
- Known allergic reaction, significant sensitivity, or intolerance to constituents of the study drugs (and excipients) and/or other products in the same class.
- Participant has the following conditions:
- Other non-AL amyloid disease;
- Previous or current diagnosis of symptomatic multiple myeloma (MM), including the presence of lytic bone disease, plasmacytomas, >= 60% plasma cells in the bone marrow, or hypercalcemia (defined as corrected calcium > 11 mg/dL);
- Active plasma cell leukemia (i.e., either 20% of peripheral white blood cells or > 2.0 × 109/L circulating plasma cells by standard differential);
- Waldenström’s macroglobulinemia;
- Acute diffuse infiltrative pneumopathy;
- Major surgery within 28 days prior first dose or planned during study participation;
- History of organ transplant requiring continued use of immunosuppressants;
- Acute infections within 14 days prior first dose requiring parenteral therapy (antibiotic, antifungal, or antiviral);
- Participant has received an autologous stem cell transplant (SCT) within 12 weeks or an allogeneic SCT within 1 year of the first dose of study drug treatment.
For more information, please contact one of the three recruiting centres in Australia, or USE THIS LINK
Sites
New South Wales
| Status: | |
| Site: | Westmead Hospital, Sydney |
| ID#: | 255200 |
Queensland
| Status: | |
| Site: | Princess Alexandra Hospital, Brisbane |
| ID #: | 255202 |
Victoria
| Status: | |
| Site: | Box Hill Hospital, Melbourne |
| ID #: | 255199 |
second relapse of Multiple myeloma and/or systemic AL amyloidosis with t(11;14)
What is the drug in question?
Iberdomide is a “CelMod”, which is similar to lenalidomide and pomalidomide. It is well tolerated with proven activity in myeloma.
It is hoped that iberdomide to be more effective and less toxic than lenalidomide in the treatment of AL amyloidosis.
Venetoclax, a BCL2 inhibitor, which used in many haematological conditions, but in myeloma and AL amyloidosis, venetoclax specifically targets the effects of t(11;14) mutation.
Who is eligible for the trial?
- Patients with AL amyloidosis who have relapsed after 1 or 2 lines of treatment previously.
- Patients must have have the t(11;14) translocation (genetic variation) detected on their bone marrow biopsy (seen in ~50% of all AL amyloidosis patients).
- Patients must have serum free light chains (SFLC) >100mg/L to qualify
How is the drug administered?
This clinical trial is designed to see if the combination of both medications with the steroid, dexamethasone, has very high response rate, has quicker response times and is well tolerated.
This is an Australian only study of 50 patients.
Note that this treatment is an all oral (tablet) treatment.
You will be given medication to minimise the risk of these side-effects.
How long does the trial go for?
The three medications will continue until it stops working or if the patient has significant sideeffects and/or wants to withdraw from the study.
While this combination is expected to be well tolerated, the more common potential sideeffects of this treatment are low blood counts, rash, infections and clots.
Sites
Victoria
| Status: | |
| Site: | Box Hill Hospital, Melbourne. |
| Contact: | Olga Motorna and Stephen Ting Email: olga.motorna@easternhealth.org.au |
| Status: | |
| Site: | St Vincent’s Hospital, Melbourne. |
| Contact: | Shirlene Sim and Hang Quach Email: shirlene.sim@svha.org.au |
Queensland
| Status: | |
| Site: | Townsville University Hospital |
| Contact: | Hock Choong Lai Email: hock.lai@health.qld.gov.au |
New South Wales
| Status: | |
| Site: | Gosford Hospital |
| Contact: | Cecily Forsyth Email: cecily.forsyth@healthmail.com.au |
| Status: | |
| Site: | Royal North Shore, Sydney |
| Contact: | Ian Kerridge Email: ian.kerridge@health.nsw.gov.au |
| Status: | |
| Site: | Liverpool Hospital |
| Contact: | Adam Bryant Email: adam.bryant1@health.nsw.gov.au |
South Australia
| Status: | |
| Site: | Royal Adelaide Hospital |
| Contact: | Angie Yong Email: Angie.Yong@sa.gov.au |
What is the drug in question?
This is a novel BCL-2 inhibitor, similar to venetoclax.
Inhibiting BCL-2 can lead to death in tumour cells dependent on BCL-2 activity, including multiple myeloma cells. Venetoclax has activity in relapsed and refractory AL amyloidosis.
This trial hopes to prove that ZN-d5 will be at least as effective as venetoclax in killing amyloid-forming plasma cells.
Who is eligible for the trial?
Patients with relapsed and refractory AL amyloidosis who have had disease relapse/progression or lack of response to 1 to 3 prior lines of therapy.
Does every patient receive the actual trial drug?
All patients will receive active drug. There is no placebo-arm to this study. ZN-d5 is not given with any other therapy.
How is the drug administered?
ZN-d5 is a oral tablet.
How long does the trial go for?
Up to 135 patients will be included in the trial. Subjects will remain on treatment until disease progression, adverse events, withdrawal of consent, death, or the end of the study.
Key inclusion criteria:
- A biopsy-confirmed diagnosis of AL amyloidosis based on one of the following: histopathology (positive Congo red-stained tissue confirmed by immunohistochemistry demonstrating light chain deposition without the presence of transthyretin), the presence of characteristic appearance on electron microscopy, or mass spectrometry typing of amyloid.
- At least 1, and no more than 3, prior lines of therapy
- Measurable disease defined by dFLC ≥ 20 mg/L.
- History of organ involvement that included at least one of the following:
- Renal: albuminuria or non-Bence Jones proteinuria > 0.5 g/day by 24-hour urine collection.
- Cardiac: mean left ventricular wall thickness on echocardiogram more than 12 mm in the absence of a history of hypertension or valvular heart disease or unexplained low voltage (< 0.5 mV) on ECG; or NT-ProBNP > 332 ng/L (or BNP > 81-ng/L) in the absence of renal failure.
- Hepatic: hepatomegaly on PE or ultrasound or alkaline phosphatase > 1.5 × the upper limit of normal (ULN).
- Gastrointestinal: direct biopsy verification of amyloid deposition and gastrointestinal symptoms, such as gastrointestinal bleeding or diarrhea.
- Neurologic: symmetrical lower extremity sensorimotor peripheral neuropathy or autonomic neuropathy, including gastric motility disorder, pseudo-obstruction, or voiding dysfunction unrelated to direct organ infiltration. Assessment of t(11;14) status by FISH on bone marrow sample.
- Adequate time since prior therapy before initiation of treatment with ZN-d5 (at least 3 months from HSCT or the shorter of 60 days or 5 half-lives from previous drug or biologic therapy or any investigational treatment).
- ECOG score of ≤ 2.
- Adequate bone marrow function as follows:
- Hemoglobin ≥ 80g/L, neutrophils ≥ 1.5 ×109/L, Platelets ≥ 50 × 109/L.
- Adequate organ function as follows:
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN.
- Alkaline phosphatase ≤ 5 × ULN.
- Total bilirubin ≤ 1.5 × ULN except for subjects with Gilbert syndrome.
- Serum albumin ≥ 2 g/dL (20 g/L).
- eGFR ≥ 30 mL/min/1.73 m2
Key exclusion criteria:
- Diagnosis of multiple myeloma according to the 2014 International Myeloma Working Group diagnostic criteria.
- Mayo 2012 Stage IV disease, defined as follows:
- NT-ProBNP ≥ 1800 ng/L, cTnT ≥ 0.025 ng/mL, dFLC ≥ 180 mg/L
- Any of the following cardiac conditions:
- New York Heart Association (NYHA) Class III or IV heart failure
- History of sustained ventricular tachycardia or fibrillation, or ventricular arrhythmias
- Corrected QT interval (QTc) > 500 msec
- Second or third-degree atrioventricular block (Mobitz type I is permitted)
- History of myocardial infarction, coronary stent placement, or coronary artery bypass grafting within 6 months of enrolment
- Left ventricular ejection fraction (LVEF) by echocardiogram < 35%
- Supine systolic blood pressure < 90 mm Hg or symptomatic orthostatic hypotension
- Positive serum antibody tests for hepatitis B surface antigen or hepatitis C
- Concurrent treatment with agents used to treat plasma cell disorders or AL amyloidosis, including experimental agents; such treatments should be discontinued the shorter of 60 days or 5 half-lives prior to first dose of ZN-d5
- Prior treatment with ZN-d5, venetoclax, navitoclax, obatoclax or any other small molecule BCL-2 inhibitor
- Any concurrent medical condition that would make a potential subject a poor candidate for this study, including uncontrolled serious infection, active malignancy other than non-melanoma skin cancer or carcinoma in situ of the cervix, uncontrolled pulmonary disease, severe diarrhea, cirrhosis, any condition likely to require systemic corticosteroids for more than 1 week during the course of this study, or major surgery within 28 days of enrolment.
For more information, please contact one of the five recruiting centres in Australia, or please review this site.
Sites
New South Wales
| Status: | |
| Site: | Blacktown Hospital |
| Contact: | Dr Fiona Kwok Email: WSLHD-TTRtrials@health.nsw.gov.au |
Queensland
| Status: | |
| Site: | Princess Alexandra Hospital |
| Contact: | Dr Emad Abro Email: amyloidosis@health.qld.org.au |
Western Australia
| Status: | |
| Site: | Sir Charles Gardiner Hospital |
| Contact: | Brad Augustson Email: Bradley.Augustson@health.wa.gov.au |
South Australia
| Status: | |
| Site: | Royal Adelaide Hospital |
| Contact: | Dr Noemi Horvath and Dr Angie Yong Email: CALHN.Amyloidtrials@sa.gov.au |
APG-2575 (varying doses) + pomalidomide and dexamethasone (Pd)
What is the drug in question?
Approximately 50% of patients with AL amyloidosis have a chromosomal (genetic) change involving part of chromosome 11 swapping with part of chromosome 14, referred to as “t(11;14)”. BCL-2 inhibitors target this mutation and can cause cell death of the plasma cells that make the amyloid. APG-2575 is a novel BCL-2 inhibitor.
In this study, APG-2575 is combined with pomalidomide, an immunomodulatory drug which has been used extensively in myeloma, and appears to be effective and well tolerated in AL amyloidosis too. Dexamethasone, a steroid, is also combined with APG-2575 and pomalidomide, to hopefully enhance the effect of the drug.
During the study, patients will be assigned different doses of APG-2575 to determine the highest dose that is the best tolerated.
Who is eligible for the trial?
Any patient with relapsed AL amyloidosis with organ involvement (eg. heart and/or kidneys), or a patient who has not achieved an excellent response to their first 3 cycles of front-line chemotherapy.
Does every patient receive the actual trial drug?
Yes, all patients receive APG-2575, pomalidomide and dexamethasone
How is the drug administered?
This is an all oral, tablet treatment
How long does the trial go for?
Patients will continue to receive treatment until disease progression, unacceptable toxicity, or withdrawal of consent.
Key inclusion criteria:
Systemic AL (not ATTR) amyloidosis, involving the heart, as proven by
- ≥ 18 years of age.
- Histochemical diagnosis based on detection by polarizing microscopy of green birefringent material in Congo red-stained tissue specimens, the type must have been confirmed unequivocally.
- Symptomatic organ involvement.
- At least one prior line of systemic therapy for AL. Patients who do not achieve at least a PR to frontline therapy in 3 months are eligible.
- All MM/AL patients should have measurable disease as defined by at least ONE of the following:
- Serum monoclonal protein 1.0 g/dl or more by protein electrophoresis.
- >200 mg of monoclonal protein in the urine on 24-hour electrophoresis.
- If both serum and urine monoclonal proteins are non-measurable:
- Serum differential FLC concentration (dFLC) > 5 mg/dL; OR serum FLC of 7.5 mg/dL provided the κ/λ FLC ratio is abnormal
- Eastern Cooperative Oncology Group (ECOG) ≤ 2.
- Life expectancy ≥ 6 months.
- Adequate hematologic function defined as:
- ANC ≥1.0 x 109/L independent of growth factor support within 7 days of the first dose with study drug.
- Haemoglobin ≥8 g/dL without transfusion or growth factor support within 7 days of the first dose of study drug.
- Platelet count ≥ 100 x 109/L or ≥ 50 x 109/L if bone marrow involvement independent of transfusion support
- Adequate hepatic and renal function defined as:
- AST and ALT < 3 x upper limit of normal
- Creatinine ≤3 mg/dL and CrCL ≥25 ml/min using the Cockcroft-Gault formula
- Bilirubin< 1.5 x ULN (except if considered secondary to Gilbert’s syndrome and primarily indirect bilirubinemia)
- PT/INR ≤2 x ULN and PTT (or aPTT) ≤2 x ULN.
- Female subjects who are of non-reproductive potential. Female subjects of childbearing potential must have a negative serum pregnancy test upon study entry.
- Male and female subjects who agree to use highly effective methods of birth control during the period of therapy and for 90 days after the last dose of study drug.
- Ability to cooperate to complete neurological examinations if required
Key exclusion criteria:
- AL amyloidosis patients who have not been treated with any systemic therapy
- AL amyloidosis clinically overt multiple myeloma i.e. original CRAB criteria. Extent of marrow plasmacytosis is not prohibitive.
- Subject has received antineoplastic therapy within 2 weeks before the date of initiating study treatment.
- Subjects planning to undergo a stem cell transplant prior to progression of disease on this study, i.e., these subjects should not be enrolled in order to reduce disease burden prior to transplant.
- Subject has peripheral neuropathy ≥grade 3 except caused by AL amyloidosis.
- Active cardiovascular disease, such as uncontrolled arrhythmia (including Frederica corrected QT interval (QTc ≥470 msec) or Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction or unstable angina.
- Major surgical procedure within ≤14 days prior to initiating study treatment, or anticipation of the need for major surgery during the course of the study treatment, radiotherapy ≤14 days prior to initiating study treatment, systemic treatment within 14 days before the first dose of APG2575.
- Recent infection requiring systemic treatment that was completed ≤14 days before the first dose of study drug.
- Subject has any concurrent or recent malignancy ≤ 1 year prior to registration with the exception of: basal or squamous cell skin cancer, any carcinoma in situ.
ACCESS CLINICAL TRAILS DATABASE HERE
Sites
Victoria
| Status: | |
| Site: | Epworth Freemasons, Melbourne |
| Contact: | Dr Brendan Wisniowski Ph: 03 8560 4010 |
Please check this website weekly for updates!
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Transthyretin Amyloidosis (ATTR) trials
Please click on the links below for more details.
Remember that there are non-trial treatments for ATTR readily available that your doctor can discuss with you. These include:
- Diflunisal – available at all AAN services
- Doxycycline
- EGCG (green tea extract)
- Tafamidis (via Pfizer access scheme)
An open-label extension (OLE) study to evaluate the long-term safety and tolerability of AT-02
What is the drug in question?
AT-02 is an investigational medicinal product being developed to treat systemic amyloidosis. AT-02 is a full-length, humanized immunoglobulin G1 (IgG1) monoclonal antibody (mAb) with a 31-amino acid peptide attached to the c-terminus of the light chain. The 31-amino acid peptide enables binding of AT-02 to all amyloid fibril types and the Fc portion of the antibody engages Fc receptors on macrophages to facilitate phagocytosis and removal of amyloid. Because AT-02 binds to existing amyloid deposits and triggers amyloid reabsorption through opsonization, it may provide clinical benefit over other therapies that rely on reduction of precursor protein synthesis or improvement of precursor protein stability to slow amyloid deposition.
What does the trial hope to prove?
Safety and efficacy of removing amyloid fibrils from the organs (heart, liver, spleen).
Who is eligible for the trial?
Male or Female aged between 18 and 90 years of age with systemic amyloidosis (AL + ATTR)
Does every patient receive the actual trial drug?
Yes
How is the drug administered?
Intravenously every 2 – 4 weeks
How long does the trial go for?
60 weeks
Key inclusion criteria:
- Subject has completed a prior study of AT-02, received AT-02 during that study, and demonstrated a favourable response without significant adverse events as determined by the investigator.
- Females of childbearing potential and males must practice effective contraception from Screening until 28 days after the EOS visit.
- Males must agree not to donate sperm for the duration of the study and for 90 days following their last dose of AT-02.
- Females of childbearing potential must have a negative pregnancy test within 24 hours prior to initial dosing of study drug.
- Able to provide Informed Consent.
- Willing and able to comply with this protocol.
Key exclusion criteria:
- Any new, clinically significant underlying illness since enrolment in the parent study.
- Any clinically significant worsening of organ function associated with underlying systemic amyloidosis or clinically significant change in concomitant medications for the treatment of systemic amyloidosis.
- eGFR < 30 mL/min/1.73 m2.
- Any female who is pregnant or breastfeeding, or any female who is planning to become pregnant during the study and follow-up period.
- Any condition that, in the investigator’s opinion, may compromise study participation, present a safety risk to the subject, or may confound the interpretation of the study results.
- Currently enrolled in another investigational device or drug study (other than the parent AT-02 study), or less than 30 days have passed since ending another investigational device or drug study.
Where to go for more information:
See below.
Sites administering the trial:
Princess Alexandra Hospital, Brisbane, Box Hill, Melbourne, Flinders, Adelaide
Sites
Victoria
| Status: | |
| Site: | Box Hill, Melbourne |
Queensland
| Status: | |
| Site: | Princess Alexandra Hospital, Brisbane |
South Australia
| Status: | |
| Site: | Flinders Medical Centre, Adelaide |
What is the drug in question?
“AT-02” is a full-length, humanised, recombinant immunoglobulin 1(IgG1)-like glycoprotein monoclonal antibody (mAb) fusion protein that has been developed to treat any form of systemic amyloidosis.
Monoclonal antibodies has been used extensively in many disease, including in AL amyloidosis. Drugs such as Daratumumab, rituximab, isatuximab and elotuzumab are all mAbs.
AT-02 has binding potency to ATTR and AL amyloid, and is thought to opsonise amyloid extracts promoting macrophage-mediated phagocytosis of the amyloid. In other words, the drug “latches onto” amyloid deposits and sends a signal to the immune system to clear deposits from the organ.
Cardiac, renal and hepatic amyloid deposits were shown to regress in mouse studies of this drug.
The most effective and highest well-tolerated dose of AT-02 in amyloidosis patients has not been determined. This Phase I trial is looking at different doses of AT-02 to see how well this drug is tolerated at a single once-off dose, and to determine the “MTD” or maximum tolerated dose.
Who is eligible for the trial?
Patients with ATTR amyloidosis with reasonable renal function (eGFR >30ml/min) are eligible
Does every patient receive the actual trial drug?
All patients will receive active drug. There is no placebo-arm to this study.
How is the drug administered?
AT-02 is an IV infusion through a drip. All patients receive paracetamol, and antihistamine and a steroid to reduce the chance of an infusion-related reaction, such as muscle aches, fevers and shakes, which are often seen during the first infusion of any mAb.
How long does the trial go for?
It is estimated that 30-40 slots will be available for patients in Australia
Patients undergo a cardiac MRI then receive a weekly IV dose of AT02 for 4 weeks
After this, they have a repeat cardiac MRI to see if the amount of amyloid in the heart has decreased.
Then 2 months later, patients will be invited to enrol in the open label extension part of the trial where patients receive a monthly maintenance IV dose to hopefully continue to remove amyloid from the heart
Key inclusion criteria:
- Biopsy-proven ATTR amyloidosis or ATTR amyloidosis proven on bone scintigraphy, provided there is no detected plasma cell dyscrasia
- Proven cardiac disease: Echocardiogram (heart ultrasound) shows wall thickness inside the heart of >11mm with elevated cardiac biomarkers (blood tests) of NT proBNP and troponin T
- Good function state (ECOG score <3) and other organ function
For more information, please contact one of the two recruiting centres in Australia, or please review :
ClinicalTrials.gov Identified: NCT05521022
Sites
Victoria
| Status: | |
| Site: | Eastern Health, Melbourne |
| Contact: | Name: Olga Motorna Email: olga.motorna@easternhealth.org.au |
Queensland
| Status: | |
| Site: | Princess Alexandra Hospital |
| Contact: | Name: Dr Dariusz Korczyk Email: amyloidosis@health.qld.org.au |
South Australia
| Status: | |
| Site: | Flinders Medical Centre |
| Contact: | Name: Fiona Wollaston Ph: 0422 512 439 |
Western Australia
| Status: | |
| Site: | Royal Perth Hospital |
| Contact: | Name: Principal Investigator: Prof Graham Hillis Study Co-ordinator: Lorraine Hillis Email: Graham.Hillis@health.wa.gov.au lorraine.hillis@health.wa.gov.au |
What is the drug in question?
NTLA-2001- clustered regularly interspaced short palindromic repeats (CRISPR) of RNAs encoding protein 9 (Cas9) formulated in lipid nanoparticle for IV use.
What does the study hope to prove?
Safety and efficacy of editing (removing) gene responsible for TTR synthesis.
Who is eligible for the trial?
Subjects with ATTR cardiomyopathy.
Does every patient receive the actual trial drug?
No. Half of them (50%) will receive placebo.
How is the drug administered?
Single intravenous infusion.
How long does the trial go for?
30 months
Key inclusion criteria:
Male and Female aged 18 to 90 years old with documented ATTR cardiomyopathy who signed the informed consent with history or current symptoms of heart failure and elevated cardiac biomarkers (NTproBNP).
Key exclusion criteria:
- Other non TTR type of Amyloidosis
- Severe heart failure (class 4 NYHA)
- Other significant cardiac cause leading to HF (CAD, valve disease etc)
- Recent (within 3 months) cardiac (heart attack) and non-cardiac (stroke, PE, DVT) event
- End stage liver disease
- Active infection
- Malignancy within preceding 3 years
- Solid organ recipient
Where to go for more information:
See below.
Sites
Victoria
| Status: | |
| Site: | Box Hill, Melbourne |
Queensland
| Status: | |
| Site: | Princess Alexandra Hospital, Brisbane |
New South Wales
| Status: | |
| Site: | Westmead Hospital, Sydney |
What is the drug in question?
ALXN2220 is a recombinant human anti-ATTR antibody that was developed for the removal of ATTR by phagocytic immune cells.
What does the study hope to prove?
Efficacy of ALXN2220 in the treatment od ATTR cardiomyopathy.
Who is eligible for the trial?
Male or Female between 18 and 90 years of age with confirmed ATTR-CM.
Does every patient receive the actual trial drug?
Randomisation is in 2:1 ratio to receive either study drug (2/3) or placebo (1/3).
How is the drug administered?
By intravenous infusion every 4 weeks.
How long does the trial go for?
48 months
Key inclusion criteria:
Subjects with confirmed ATTR-CM, history or current heart failure (class 2-4 NYHA dyspnoea) and elevated cardiac biomarkers (NTproBNP).
Key exclusion criteria:
- Other non TTR types of amyloidosis
- Cardiomyopathy caused by other condition
- Recent (within 3 months) acute CV event
- Low LV ejection fraction (<30%)
- Severe non cardiac medical illness (lung, liver, kidney)
- Malignancy within last 5 years
- Solid organ recipient
- Low body weight (<40kg)
Where to go for more information:
See below.
Sites
Victoria
| Status: | |
| Site: | Box Hill, Melbourne |
| Status: | |
| Site: | The Alfred, Melbourne |
Queensland
| Status: | |
| Site: | Princess Alexandra Hospital, Brisbane |
New South Wales
| Status: | |
| Site: | Westmead Hospital, Sydney |
| Status: | |
| Site: | St Vincent’s Hospital, Sydney |
Western Australia
| Status: | |
| Site: | Joondalup, Perth |