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. Clinical trials shown on this page are updated regularly; however, patients and physicians are encouraged to contact participating clinical trial centres directly for the most up-to-date information.
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:
Trials by State
Use the map at left
to view trials in your state.
Click on each state for location detail.
New South Wales & ACT
AL Trials
Etentamig (ABBV383) M24-209
ATTR Trials
MAGNITUDE: A Phase 3 study of NTLA-2001
CAPACE
AG10-501
Victoria & Tasmania
All Types
Positron Emission Tomography with AT-01
AL Trials
Etentamig (ABBV383) M24-209
APG2575MU101
ATTR Trials
MAGNITUDE: A Phase 3 study of NTLA-2001
TRITON-CM
Queensland
All Types
Positron Emission Tomography with AT-01
AL Trials
Etentamig (ABBV383) M24-209
Development of personalised mRNA vaccines
ATTR Trials
MAGNITUDE: A Phase 3 study of NTLA-2001
Northern Territory
There are currently no trials operating in the Northern Territory
All Types of Amyloid
Positron Emission Tomography with AT-01 : – (open to all types of amyloid).
- Positron Emission Tomography with AT-01 to Diagnose and Monitor Amyloidosis: A Prospective Cohort Pilot Study in Adult Patients.
- ACTRN12624000755538
What is the drug in question?
AT-01 is a novel peptide radiotracer which binds to a constant region of the insoluble amyloid protein; the agent which results in end-organ damage in amyloidosis. It is able to demonstrate on molecular imaging scans the presence of amyloid within all vital organs of the body, namely the heart, kidneys, liver and spleen. No other imaging modality has been able to capture this in a single scan. By accurately detecting amyloid in organs of the body and assessing for response to therapy, AT-01 PET/CT scans have the potential to revolutionise the way amyloidosis is diagnosed, monitored, and help to guide treatment decisions in the future.
Who is eligible for the trial?
- Newly diagnosed systemic amyloidosis – all subtypes
- Systemic AL amyloidosis with suboptimal response to therapy or in early biochemical relapse.
Does every patient receive the actual trial drug?
Yes
How is the drug administered?
The drug is given through an IV (drip into the vein).
How long does the trial go for?
2 years
Key inclusion criteria:
- Diagnosis of amyloidosis with the known following subtype:
(a) Systemic AL amyloidosis prior to therapy commencement (n=15)
(b) Systemic AL amyloidosis with suboptimal response to therapy or in early biochemical relapse (n=5)
(c) ATTRwt amyloidosis (n=5)
(d) Other systemic amyloidosis i.e. ALECT2 and Alys amyloidosis (n=5) - Age equal to or greater than 18yrs
- Life expectancy greater than 3 months
Key exclusion criteria:
Subjects must meet none of the following criteria:
- Localised amyloidosis
- Known iodine or potassium iodide hypersensitivity
- Patients being treated with heparin and heparin like anticoagulant therapy (due to interaction with AT-01)
- Patients who are pregnant and/or breastfeeding
Sites
Victoria
| Status: | |
| Site: | Eastern health (Box Hill Hospital), Melbourne |
| Contact: | Dr Brendan Wisniowski Brendan.Wisniowski@easternhealth.org.au |
Queensland
| Status: | |
| Site: | Princess Alexandra Hospital |
| Contact: | Amyloidosis@health.qld.gov.au |
Patients will have access to clinical trial data
Systemic Light Chain Amyloidosis (AL) trials
Newly diagnosed:
None current.
Previously treated:
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.
- dFLC Cutoff either ≥50 mg/L or High-risk dFLC progression after immediate prior line of therapy defined as meeting all of the following criteria:
- >20 mg/L
- >20% of baseline value before initiation of prior therapy
- >50% of nadir at best response to prior therapy
- Cardiac Risk Stage: Patients considered AL amyloidosis cardiac risk stage 1, 2, or 3a, or considered cardiac risk stage 3b with stable cardiac function and biomarkers for 3 months prior to dosing with no cardiac-related hospitalizations within 3 months and no changes to diuretic regimen within 21 days of first dose of study treatment.
- 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 |
| Contact: | Dr Fiona Kwok wslhd-hct@health.nsw.gov.au |
Queensland
| Status: | |
| Site: | Princess Alexandra Hospital, Brisbane |
| Contact: | Dr Peter Mollee Amyloidosis@health.qld.gov.au |
Victoria
| Status: | |
| Site: | Eastern health (Box Hill Hospital), Melbourne |
| Contact: | Dr Olga Motorna olga.motorna@easternhealth.org.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 |
What is the treatment/drug being studied?
Teclistamab (brand name Tecvayli) is a bispecific antibody immunotherapy for treating relapsed/refractory multiple myeloma, activating T-cells to kill cancer cells by targeting BCMA on myeloma cells and CD3 on T-cells, given as subcutaneous injections with serious risks like cytokine release syndrome (CRS) and neurotoxicity, requiring careful patient monitoring, especially during initial dosing.
Who is eligible for the trial?
Relapsed patients must have received at least 1 line of treatment, including Dara and bortezomib. Patients must have received at least two cycles of therapy.
Will all participants receive the trial drug?
Yes all patients will receive Teclistamab – no placebo.
How is the treatment given?
Given as a subcutaneous injections with serious risks like cytokine release syndrome (CRS) and neurotoxicity, requiring careful patient monitoring, especially during initial dosing.
How long does the trial last?
Subjects will receive teclistamab according to the dosing schedule, for 6 cycles, or until PD, death, intolerable toxicity, withdrawal of consent, or end of the trial, whichever occurs first. To continue treatment beyond cycle 6, up to a maximum of 12 cycles, sponsor’s approval will be required.
Key inclusion criteria:
- Confirmed diagnosis of AL amyloidosis
- ECOG 0-2
- Measurable disease dFLC >20mg/L
- At least one symptomatic organ involved
- Adequate organ function
- Eastern Cooperative Oncology Group (ECOG) ≤ 2.
- Life expectancy ≥ 6 months.
Key exclusion criteria:
- Non AL amyloidosis
- Previous BCMA targeted therapy
- MM diagnosis as per IMWG criteria, with exception of SFLC ratio >100
- Intolerance to dexamethasone
Sites
South Australia
| Status: | |
| Site: | Royal Adelaide Hospital |
| Contact: | Study Coordinator – Rino Amato Ph: 0) 7074 5719 |
Correlative research:
Study Summary
- Immunoglobulin light chain (AL) amyloidosis is the most common form of systemic amyloidosis. Abnormal clonal bone marrow plasma cells secrete AL that cause a host of systemic effects. Current treatments focus on the eradication of these abnormal plasma cells but are unable to differentiate between normal and abnormal plasma cells.
- This biomedical lab study aims to stimulate a patient’s immune system to only target the abnormal plasma cells that cause their disease. This study will look at the efficacy of personalised mRNA vaccines in-vitro.
Who is eligible for the trial?
Participants with suspected, confirmed or relapsed/refractory AL amyloidosis, who are currently not on treatment.
What do patients need to do?
For this biomedical lab study, bone marrow aspirate and peripheral blood are required from participants. No other participation is required.
How long does the trial go for?
This study will run for 3 years.
Anything else I need to know?
As this is a lab study, there will be no treatment offered to participants. The samples collected from participants will confirm if our approach is applicable for patients with AL amyloidosis. We hope this study will inform future clinical trials that offer personalised mRNA vaccines for patients with AL amyloidosis and related disorders.
Sites
Queensland
| Status: | |
| Site: | Princess Alexandra Hospital, Brisbane |
| Contact: | Muhammed B. Sabdia m.bilalsabdia@mater.uq.edu.au |
Please check this website weekly for updates!
Transthyretin Amyloidosis (ATTR) trials
Please click on the links below for more details.
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. Randomisation is in 2:1 ratio to receive either study drug (2/3) or placebo (1/3).
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: | Eastern Health (Box Hill Hospital), Melbourne |
| Contact: | Brendan.Wisniowski@easternhealth.org.au |
| Status: | |
| Site: | Alfred Health, Melbourne |
| Contact: | cardiacamyloid@alfred.org.au |
Queensland
| Status: | |
| Site: | Princess Alexandra Hospital, Brisbane |
| Contact: | Amyloidosis@health.qld.gov.au |
New South Wales
| Status: | |
| Site: | Westmead Hospital, Sydney |
| Contact: | WSLHD-TTRtrials@health.nsw.gov.au |
Australian Capital Territory
| Status: | |
| Site: | Canberra Hospital |
| Contact: | Erin.Clark@act.gov.au and Wichat.Srikusalanukul@act.gov.au |
Western Australia
| Status: | |
| Site: | Fiona Stanley Hospital |
| Contact: | Kaitlyn.Lam@health.wa.gov.au |
South Australia
| Status: | |
| Site: | Royal Adelaide Hospital |
| Contact: | Name: Denise Healy Email: denise.healy@sa.gov.au |
New Zealand
| Status: | |
| Site: | New Zealand Clinical Research (NZCR) Auckland and Christchurch |
| Contact: | Timothy.Sutton@middlemore.co.nz |
Optimal heart rates in patients with Cardiac Amyloidosis and pacemakers
Study intervention and description of involvement:
- Prospective pilot study of cardiac pacing augmented myocardial dynamics in patients with transthyretin cardiac amyloidosis. The study includes enrolment then two site study visits and a final phone call at 1 year.
- During the first visit a patient will undergo clinical assessment with physical examination, quality of life survey, 6 minute walk test, electrocardiogram (ECG), echocardiogram and cardiac magnetic resonance imaging (CMR) at three different pacing rates, assessing the cardiac response to each heart rate. Cardiac device pacing rate will then be set to the individually optimised pacing rates as per CMR for one month.
- The second visit at one month will include brief physical examination, quality of life survey, 6 minute walk test, electrocardiogram (ECG), echocardiogram. Cardiac devices will be interrogated to confirm the heart rate paced during the prior intervention period and reprogrammed to their original settings.
Patients will receive a brief follow up phone call at 1 year.
Inclusion criteria:
- People who meet diagnostic criteria for transthyretin cardiac amyloidosis
- Cardiac implantable electronic device (pacemakers or defibrillator) which is MRI compatible.
- Underlying native heart rate of 60 beats per minute or less.
- Willingness to give written informed consent and willingness to participate to and comply with the study
Exclusion criteria:
- Patients with any contraindications for CMR imaging including:
- Patients with previous allergy to gadolinium.
- Patients with a history of significant renal impairment (eGFR<30ml/min/1.73m2).
- Patients who are medically unstable.
- Patients with claustrophobia.
- Cardiac pacemakers or implantable cardioverter defibrillator not deemed to be MRI compatible.
- Pregnancy or lactating.
- Orbital foreign bodies from metal injury to the eye.
- Intracranial metal clips.
- Non-MRI compatible stapes implants.
- Programmable Hydrocephalus Shunts.
- Large metal implants.
- Patients with a history of a psychological illness or condition such as to interfere with the patient’s ability to understand the requirements of the study.
Where to go for more information:
Name Dr Natasha Gorrie
Email: natasha.gorrie@svha.org.au
Sites
New South Wales
| Status: | |
| Site: | St Vincent’s Hospital, Sydney |
What is the treatment/drug being studied?
Nucresiran is a TTR silencer. It is like a “quiet button” that turns down the amount of the disease-causing protein that is made. Because there is less TTR, there may be less buildup in the heart and other organs over time.
Who is eligible to take part?
You must have a diagnosis of transthyretin amyloidosis (ATTR) with decreased heart muscle function or cardiomyopathy.
Will all participants receive the trial drug?
The Study Medication will either be 300 mg of nucresiran or placebo, which only contains saline, a fluid of salt and water. This study will use 2:1 randomisation, which means you have a 2 out of 3 (67%) chance of receiving nucresiran.
How is the treatment given?
The study medication is administered every 6 months with a small needle under the skin (it does not go into the muscle) in your belly, upper arm, or thigh.
How long does the trial last?
Your participation in this study may last for 5-8 years with the study being divided into 2 parts. However, due to the study design, the length of this study could vary for each participant, ranging from a minimum of 24 months to approximately 5 years.
Part 1 of the trial is where you are randomized to receive the study drug nucresiran or placebo. There are approximately 13 study visits over an average length of 3 years.
Part 2 of the study is where everyone will receive nucresiran (no placebo) and is expected to last for 2 years. Study visits will be every 6 months.
Key inclusion criteria:
- Age 18 to 85 years
- A diagnosis of transthyretin amyloidosis (ATTR) with decreased heart muscle function or cardiomyopathy
- A history of being hospitalised for heart failure or currently taking a tablet called lasix or frusemide
Key exclusion criteria:
- Diagnosis of AL Amyloidosis
- If you require a cane or stick to walk due to severe leg weakness or you are wheelchair bound
- You have previously received other medication for ATTR lowering such as TTR depleter agents, vutrisiran or gene therapy targeting ATTR
- Current participation in another trial
- Female participants planning to become pregnant
Sites
Victoria
| Status: | |
| Site: | Eastern Health (Box Hill Hospital), Melbourne |
| Contact: | Brendan.Wisniowski@easternhealth.org.au |
South Australia
| Status: | |
| Site: | Flinders Medical Centre, Bedford Park |
| Contact: | Fiona.wollaston2@sa.gov.au |
| Status: | |
| Site: | Royal Adelaide Hospital |
| Contact: | Denise.healy@sa.gov.au |
What is the treatment/drug being studied?
Acoramidis
Who is eligible for the trial?
In Participants aged 18-75 with pathogenic TTR variant. This study aims to determine the efficacy of acoramidis to prevent ATTR in individuals who carry a known pathogenic TTR variant with no clinical evidence of amyloidosis. Up to approximately 582 participants will be enrolled.
Will all participants receive the trial drug?
Study participants will have a 50% (1 in 2) chance of receiving 712 mg acoramidis tablets orally twice daily or a 50% (1 in 2) chance of receiving matching placebo orally twice daily.
How is the treatment given?
Oral tablets, two tablets twice a day.
How long does the trial last?
7 years, if participant has showed cardiac symptom, then this participant will enter open label trial AG10-504 study.
Key inclusion criteria:
- Male or female ≥ 18 to ≤ 75 years of age inclusive when signing the informed consent
- Established genotype of a TTR gene variant that is known to be pathogenic (eg, V30M/p.V50M, V122I/p.V142I, T60A/p.T80A, or all other pathogenic TTR variants) confirmed by central laboratory prior to randomization
- Participants with rare pathogenic TTR variants documented to be cardiac radionuclide uptake negative (eg, S77Y/p.S97Y, Y114C/p.Y134C, E92K/p.E112K, F64L/p.F84L, or other variant) may be included in the trial, provided the participant can be assessed for the primary ATTR-CM endpoint with:
- Echocardiography with strain suggestive of cardiac amyloidosis AND an endomyocardial biopsy with confirmatory TTR amyloid typing, OR
- CMR suggestive of cardiac amyloidosis AND an endomyocardial biopsy with confirmatory TTR amyloid typing
- In the case of these rare TTR variants documented to be cardiac radionuclide uptake negative, screening echocardiography with strain and CMR must be essentially normal (ie, not suggestive of ATTR-CM) according to the Investigator
- Participant’s age is no more than10 years (≤ 10) younger than the PADO as determined by pedigree analysis or TTR Variant Actuarial Table for their variant (Scenarios 4A, 4B, or 4C). The participant may be older than PADO. For example, if PADO for a given participant is determined to be 50 years, the age that participant must be is at least 40 years of age (≥ 40) and less than or equal to 75 years of age (≤ 75) (see Table 5). Please refer to Genotype Manual for details on calculation of PADO. 4A. If on pedigree analysis, the participant has an established family history (in at least TWO affected relatives) with documented ATTRv, as defined in the Genotype Manual, due to the same pathogenic TTR variant, PADO should be based on the MEDIAN age of ATTRv diagnosis onset within their kindred. See Genotype Manual for details on determination of pedigree-based PADO. OR
- 4B. If on pedigree analysis, the participant has a family history in ONLY ONE affected relative with documented ATTRv, as defined in the Genotype Manual, due to the same pathogenic TTR variant, the younger of the two values between the age of that affected relative and the age listed in the TTR Variant Actuarial Table (Genotype Manual) should be assigned as the PADO. See Genotype Manual for further details on determination of actuarial table-based PADO. OR
- 4C. If the participant has NO family history from which to determine PADO, the TTR Variant Actuarial Table should be used to determine PADO. See Genotype Manual for further details on determination of actuarial table-based PADO.
Note: Homozygosity for the V122I/p.V142I TTR variant is associated with earlier onset of disease (Reddi et al. 2014). Therefore, participants who are found to be homozygous for V122I/p.V142I, regardless of family history, must enroll through IC4C and refer to the homozygous V122I/p.V142I row in the TTR Variant Actuarial Table for determination of PADO (Reddi et al. 2014).
Note: Participants found to have more than one pathogenic TTR variant (e.g., compound heterozygotes) may qualify for enrollment in this trial. Therefore, participants who are found to have more than one pathogenic TTR variant, regardless of family history, must enroll through IC4C and refer to the TTR Variant Actuarial Table for determination of PADO using the youngest variant.
Key exclusion criteria:
- Myocardial radionuclide uptake of Grade 1–3 on planar imaging, confirmed by SPECT
- Evidence of ATTR-PN (including autonomic neuropathy) by SNAC examination or skin biopsy
- Known history of AL amyloidosis or non-TTR amyloid subtype (e.g., ApoA-1, gelsolin)
- History of monoclonal paraprotein or abnormal light chains (i.e., MGUS) where AL amyloidosis has not been ruled out
- Pre-existing diagnosis of axonal neuropathy from non-amyloid cause (e.g., diabetic peripheral neuropathy, alcohol-related neuropathy)
- Presence of phenotypically protective TTR variant (e.g., T119M, R104H)
- Current or recent treatment with ATTR therapies: patisiran/inotersen/tafamidis (within 3 months); ATTR-oriented products (within 1 month); second-generation TTR knockdown agents (within 6 months, e.g., vutrisiran, eplontersen); monoclonal antibody TTR amyloid depleters (within 12 months)
Sites
New South Wales
| Status: | |
| Site: | Westmead Hospital |
| Contact: | WSLHD-TTRtrials@health.nsw.gov.au |
