Phase I Study of AT-02 in Healthy Volunteers and Subjects With Systemic Amyloidosis (AT02-001)
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 any type of systemic amyloidosis with organ involvement with amyloid but reasonable kidney function (eGFR >30ml/min) are eligible. Patients with only localised disease or those with poor rkidney function are not 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 14 patients will participate in this study to determine the MTD. Patients will be followed up for 3 months by the trials team after the dose is administered, in addition to their regular reviews with their treating amyloid specialist.
However, there will be another study following this one, where patients will receive 4 x weekly IV infusions of AT-02. There will be scans of the heart and liver before and after the 4 infusions, to see if there is any evidence of amyloid regression.
Key inclusion criteria:
- A biopsy-confirmed diagnosis of 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.
- 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.
- ECOG score of ≤ 2.
- 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
For more information, please contact one of the two recruiting centres in Australia, or please review :
ClinicalTrials.gov Identified: NCT05521022