What side effects are associated with this type of intervention?

Common treatments for amyloidosis include monoclonal antibodies like Birtamimab, proteasome inhibitors (e.g., bortezomib), immunomodulatory drugs (e.g., lenalidomide), and autologous stem cell transplantation. Known side effects of these treatments can include cytopenias, gastrointestinal distress, peripheral neuropathy, fatigue, edema, and increased risk of infections. Specifically, monoclonal antibodies may cause infusion-related reactions, hypersensitivity, and potential organ-specific toxicities. Proteasome inhibitors are associated with neuropathy and gastrointestinal issues, while immunomodulatory drugs can lead to cytopenias and fatigue. Autologous stem cell transplantation carries risks of mucositis, infections, and organ toxicity.

What prior FDA approvals exist?

Several treatments for amyloidosis have been explored, with a focus on monoclonal antibodies and proteasome inhibitors. Daratumumab, a monoclonal antibody, has shown efficacy in treating AL amyloidosis, particularly in patients with severe cardiac involvement. It is often used in combination with other drugs like cyclophosphamide, bortezomib, and dexamethasone (CyBorD). Bortezomib, a proteasome inhibitor, is another key drug used in various regimens for AL amyloidosis. While specific FDA approvals for these treatments in amyloidosis are not detailed, their use in clinical practice highlights their importance in managing the disease.

What other types of research exist?

Promising alternatives to Birtamimab for amyloidosis patients include Tafamidis, which has shown efficacy in reducing mortality and cardiovascular-related hospitalizations in ATTR amyloidosis, and Vutrisiran, an RNA interference therapy approved for transthyretin amyloidosis. Additionally, Patisiran and Inotersen are RNA interference therapies that have demonstrated safety and efficacy in clinical trials for transthyretin amyloidosis.

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Monoclonal Antibodies

Birtamimab for Amyloidosis (AFFIRM-AL Trial)

Phase 3

Recruiting

Research Sponsored by Prothena Biosciences Ltd.

Eligibility Criteria Checklist

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

Must have

Confirmed Mayo Stage IV AL Amyloidosis as defined by NT-proBNP ≥1800 pg/mL and Troponin-T ≥0.025 ng/mL or high sensitivity cardiac troponin T≥40ng/L and dFLC ≥18 mg/dL

Planned first-line chemotherapy contains bortezomib administered subcutaneously weekly.

Must not have

Subject is eligible for and plans to undergo ASCT or organ transplant during the study

Prior treatment with hematopoietic growth factors, transfusions of blood or blood products within 1 week of Month 1-Day 1

Timeline

Screening 3 weeks

Treatment Varies

Follow Up month 9

Awards & highlights

Pivotal Trial

Summary

This trial tests birtamimab, a new drug, in patients with severe AL amyloidosis. The drug aims to clear harmful protein buildups in the body, potentially improving patient outcomes.

Who is the study for?

This trial is for adults with Mayo Stage IV AL Amyloidosis, a condition affecting the heart due to abnormal protein deposits. Participants must be newly diagnosed, treatment-naïve with specific cardiac involvement markers, and planning first-line chemotherapy including bortezomib. Those eligible for transplants or having other conditions like multiple myeloma or recent heart issues cannot join.

What is being tested?

The study compares the effectiveness of Birtamimab plus standard chemotherapy against a placebo combined with standard chemotherapy in treating AL Amyloidosis patients at an advanced stage. It's designed to see if Birtamimab can improve patient outcomes.

What are the potential side effects?

While not specified here, treatments like Birtamimab may cause side effects such as allergic reactions, infusion-related symptoms, fatigue, nausea, and could potentially worsen underlying heart conditions.

Eligibility Criteria

Inclusion Criteria

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

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My tests show I have advanced AL Amyloidosis with specific heart and blood markers.

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My first chemotherapy will include weekly bortezomib shots.

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I have been diagnosed with AL amyloidosis.

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I have newly diagnosed AL amyloidosis with heart involvement and haven't received treatment.

Exclusion Criteria

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

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I am planning to have a stem cell or organ transplant.

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I haven't received blood products or growth factors in the last week.

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My condition is not light-chain (AL) amyloidosis.

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I have previously received treatments targeting my amyloid condition.

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I have Waldenström's macroglobulinemia or a related condition.

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I have a severe heart valve problem or a serious heart condition from birth.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ month 9

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~month 9

This trial's timeline: 3 weeks for screening, Varies for treatment, and month 9 for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Time to all-cause mortality for the Double Blind Phase

Secondary study objectives

6MWT distance for the Double Blind Phase

Physical Component Summary score of the Short Form-36, version 2 for the Double Blind Phase

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: Birtamimab plus Standard of Care Chemotherapy- For Double-blind Phase and OLE Phase of studyExperimental Treatment2 Interventions

Intravenous administration of 24 mg/kg birtamimab every 28 days. Drug: Standard of Care Chemotherapy. Bortezomib-containing chemotherapy regimen (e.g. cyclophosphamide, bortezomib, and dexamethasone (CyBorD)) according to the institutional standard of care. The initiation of daratumumab treatment at randomization is allowed at the discretion of the Investigator; initiation at any other time during the Double-blind Phase is prohibited. For subjects who did not initiate daratumumab at randomization during the Double-blind Phase, daratumumab may be initiated at any time during the OLE Phase at the Investigator's discretion.

Group II: Placebo plus Standard of Care Chemotherapy- For Double-blind Phase of studyPlacebo Group2 Interventions

Intravenous 0.9% Saline administration as a placebo every 28 days. Drug: Standard of Care Chemotherapy. Bortezomib-containing chemotherapy regimen (e.g. cyclophosphamide, bortezomib, and dexamethasone (CyBorD)) according to the institutional standard of care. Initiation of daratumumab at randomization allowed at the discretion of the investigator.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Standard of Care Chemotherapy

2014

Completed Phase 2

~270

0 / 10Eligibility 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

Common treatments for Amyloidosis include monoclonal antibodies, proteasome inhibitors, and immunomodulatory drugs. Monoclonal antibodies, such as Birtamimab, target and bind to amyloid deposits, promoting their clearance from tissues. Proteasome inhibitors like bortezomib disrupt the degradation of misfolded proteins, reducing the formation of amyloid fibrils. Immunomodulatory drugs, such as lenalidomide, enhance the immune system's ability to target and destroy abnormal plasma cells producing amyloidogenic light chains. These treatments are crucial for Amyloidosis patients as they address the underlying mechanisms of amyloid formation and deposition, thereby improving organ function and patient outcomes.

Systemic Amyloidosis: a Contemporary Overview.