What is the mechanism of action of this treatment?

The most common treatments for AL Amyloidosis include monoclonal antibodies like CAEL-101, which target and remove amyloid deposits from tissues and organs. These antibodies work by binding to the amyloid fibrils, facilitating their clearance through immune-mediated mechanisms such as complement activation and phagocytosis. This is crucial for AL Amyloidosis patients as it helps to reduce the toxic effects of amyloid accumulation, potentially improving organ function and overall survival. Other treatments focus on controlling the underlying plasma cell dyscrasia to reduce the production of amyloidogenic light chains, thereby preventing further amyloid formation.

What side effects are associated with this type of intervention?

Common treatments for AL Amyloidosis, particularly monoclonal antibodies like CAEL-101, include agents such as daratumumab. Known side effects of these treatments often include infusion-related reactions, infections, gastrointestinal disorders, and hypersensitivity reactions. Other adverse effects may include headache, falls, and diarrhea. These treatments aim to remove amyloid deposits and improve organ function but require careful monitoring for these potential side effects.

What prior FDA approvals exist?

The FDA has approved several treatments for AL Amyloidosis, focusing on different mechanisms. One notable monoclonal antibody is daratumumab, which has shown high rates of hematologic response in patients with relapsed or refractory AL amyloidosis. Daratumumab works by targeting CD38 on plasma cells, leading to their destruction. Other treatments include RNA interference therapies like patisiran and vutrisiran, which reduce the production of amyloidogenic proteins. While these treatments differ from CAEL-101, which directly removes AL amyloid deposits, they represent significant advancements in managing AL amyloidosis.

What other types of research exist?

Promising alternatives to CAEL-101 for AL Amyloidosis include daratumumab, which targets CD38 on plasma cells and has shown efficacy in previously treated patients. Other potential treatments include NEOD001, 11-1F4, and anti-SAP antibodies, although they require further validation. Additionally, ixazomib, lenalidomide, and dexamethasone have been used in relapsed or refractory cases with positive outcomes.

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Monoclonal Antibodies

CAEL-101 for Amyloidosis

Phase 3

Waitlist Available

Research Sponsored by Alexion

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Histopathological diagnosis of amyloidosis based on polarizing light microscopy of green bi-refringent material in Congo red stained tissue specimens AND confirmation of AL derived amyloid deposits by at least one of the following: Immunohistochemistry/Immunofluroescence, Mass spectrometry, Characteristic electron microscopy appearance/Immunoelectron microscopy

Planned first-line treatment for plasma cell dyscrasia is a cyclophosphamide-bortezomib-dexamethasone (CyBorD)-based regimen administered as SoC

Must not have

Has POEMS (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes) syndrome or multiple myeloma defined as clonal bone marrow plasma cells > 10% from a bone marrow biopsy (performed ≤ 3 months prior to signing the ICF) or biopsy-proven (performed ≤ 3 months prior to signing the ICF) bony or extramedullary plasmacytoma AND one or more of the following CRAB features: Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically: Hypercalcemia, Renal insufficiency, Anemia, Bone lesions, Any one of the following biomarkers of malignancy

Have any other form of amyloidosis other than AL amyloidosis

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 50 weeks

Awards & highlights

Pivotal Trial

Summary

This trial is testing CAEL-101, a special medicine, in patients with severe AL amyloidosis. The goal is to see if it helps clear harmful protein deposits from their organs and improves their survival. The study will compare CAEL-101 with standard treatments.

Who is the study for?

This trial is for patients with Mayo Stage IIIa AL Amyloidosis, a condition where abnormal proteins build up in organs. Participants must have heart involvement, measurable hematologic disease, and agree to use effective contraception. Those with other amyloidosis types or prior treatments for AL amyloidosis (except limited CyBorD regimen) are excluded.

What is being tested?

The study tests CAEL-101's effectiveness and safety against placebo when added to the standard CyBorD treatment regimen. CAEL-101 is an antibody designed to clear out harmful protein deposits from tissues in patients with advanced cardiac AL Amyloidosis.

What are the potential side effects?

Potential side effects of CAEL-101 may include allergic reactions due to the body's immune response, infusion-related reactions during administration, and possible impacts on organ function as it targets protein deposits.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My diagnosis of amyloidosis was confirmed with specific tests on tissue samples.

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My first treatment for my blood disorder will be with CyBorD.

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My condition is stage IIIa AL amyloidosis with NT-proBNP > 650 ng/L.

Select...

I have heart issues due to AL amyloidosis, confirmed by tests.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I have POEMS syndrome or multiple myeloma with specific symptoms or test results.

Select...

My condition is not AL amyloidosis.

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My blood pressure is very low or drops significantly when I stand up, despite treatment.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 50 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~50 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and 50 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Secondary study objectives

Change From Baseline to Week 50 in Distance Walked (in Meters) during a Six-minute Walk Test (6MWT)

Change From Baseline to Week 50 in Global Longitudinal Strain (GLS%)

Change From Baseline to Week 50 in the Kansas City Cardiomyopathy Questionnaire-Overall Score (KCCQ-OS)

+2 more

Other study objectives

24-hour Urine Protein Measure

Assessment of limitation during physical activity

Changes in Amyloid Load of the Heart, Liver and Spleen

+13 more

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: CAEL-101 combined with SoC plasma cell dyscrasiaExperimental Treatment2 Interventions

The study is divided into 2 parts, the Primary Study and the Open-Label Extension Study. CAEL-101 is administered as an intravenous (IV) infusion over approximately 2 hours. It is planned that all patients will continue their double-blind treatment until the last patient is randomized in the study plus 18 months.

Group II: Placebo combined with SoC plasma cell dyscrasiaPlacebo Group2 Interventions

Patients randomized to receive placebo will receive 0.9% normal saline in an equivalent volume to a CAEL-101 infusion (approximately 250 cc). It is planned that all patients will continue their double-blind treatment until the last patient is randomized in the study plus 18 months.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

CAEL-101

2020

Completed Phase 2

~30

0 / 7Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for AL Amyloidosis include monoclonal antibodies like CAEL-101, which target and remove amyloid deposits from tissues and organs. These antibodies work by binding to the amyloid fibrils, facilitating their clearance through immune-mediated mechanisms such as complement activation and phagocytosis. This is crucial for AL Amyloidosis patients as it helps to reduce the toxic effects of amyloid accumulation, potentially improving organ function and overall survival. Other treatments focus on controlling the underlying plasma cell dyscrasia to reduce the production of amyloidogenic light chains, thereby preventing further amyloid formation.

Targeting Amyloid Fibrils by Passive Immunotherapy in Systemic Amyloidosis.Emerging therapeutic targets currently under investigation for the treatment of systemic amyloidosis.A clinico-epidemiological study of macular amyloidosis from north India.