CAEL-101 for Amyloidosis

Recruiting at 327 trial locations

Overseen By Alexion Pharmaceuticals, Inc

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Alexion

Must be taking: CyBorD regimen

Disqualifiers: Other amyloidosis, Multiple myeloma, POEMS, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 50 weeks

281 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, it mentions that participants should not have received prior therapy for AL amyloidosis or multiple myeloma, except for a limited exposure to a specific treatment regimen. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug CAEL-101 for amyloidosis?

The CyBorD regimen, which is part of the treatment being studied, has shown effectiveness in treating AL amyloidosis by producing rapid and complete responses in many patients. It is well tolerated and has been used successfully in patients with multiple organ involvement. ^{1 2 3 4 5}

Is CAEL-101 safe for humans?

The safety data for CAEL-101 specifically is not available, but similar treatments like CyBorD, which includes some of the same components, have been generally well tolerated in patients with AL amyloidosis, showing few side effects and no new safety concerns in trials. ^{1 2 5 6 7}

How does the drug CAEL-101 differ from other treatments for amyloidosis?

The treatment CAEL-101 is unique because it is being studied in combination with the CyBorD regimen, which includes cyclophosphamide, bortezomib, and dexamethasone, known for inducing rapid responses in AL amyloidosis. This combination aims to enhance outcomes, especially in high-risk groups, by potentially offering a novel mechanism of action or improved efficacy compared to existing treatments. ^{1 2 5 8 9}

What is the purpose of this trial?

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.

Research Team

Scott Swenson, MD

Principal Investigator

Alexion, AstraZeneca Rare Disease

Eligibility Criteria

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.

Inclusion Criteria

Patients must be at least 18 years of age

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

Women of childbearing potential (WOCBP) must have a negative pregnancy test during Screening and must agree to use highly effective contraception from Screening to at least 5 months following the last study drug administration or 12 months following the last dose of her PCD therapy, whichever is longer

Exclusion Criteria

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

My condition is not AL amyloidosis.

I have been treated for AL amyloidosis or multiple myeloma, but only briefly used a specific treatment regimen.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CAEL-101 or placebo combined with standard of care plasma cell dyscrasia treatment

50 weeks

Regular visits for treatment administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

18 months

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• CAEL-101
• CyBorD regimen
• Placebo

Trial Overview 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.

Participant Groups

Group I: CAEL-101 combined with SoC plasma cell dyscrasia Experimental Treatment 2 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 dyscrasia Placebo Group 2 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.

Who Is Running the Clinical Trial?

Alexion

Lead Sponsor

Trials

247

Recruited

38,600+

Marc Dunoyer

Alexion

Chief Executive Officer since 2021

PhD in Molecular Biology, University of Brussels

Christophe Hotermans

Alexion

Chief Medical Officer since 2021

MD, University of Leuven

Alexion Pharmaceuticals, Inc.

Lead Sponsor

Trials

267

Recruited

141,000+

Dr. Alberto R. Martinez

Alexion Pharmaceuticals, Inc.

Chief Medical Officer since 2010

MD from University of Sao Paulo

Marc Dunoyer

Alexion Pharmaceuticals, Inc.

Chief Executive Officer since 2021

PhD in Molecular Biology

Alexion Pharmaceuticals

Lead Sponsor

Trials

231

Recruited

36,700+

Marc Dunoyer

Alexion Pharmaceuticals

Chief Executive Officer since 2021

B.A. in Psychology from the University of New Hampshire

Christophe Hotermans

Alexion Pharmaceuticals

Chief Medical Officer since 2023

MD

Caelum Biosciences

Lead Sponsor

Trials

3

Recruited

430+

Caelum Biosciences, Inc.

Lead Sponsor

Trials

3

Recruited

430+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Findings from Research

The combination therapy of daratumumab, cyclophosphamide, bortezomib, and dexamethasone (daratumumab-CyBorD) has become the new standard-of-care for systemic light chain (AL) amyloidosis, showing high rates of hematologic and organ response.

Recent advancements in patient selection and induction regimens have significantly reduced the mortality associated with autologous stem cell transplant (ASCT), while new treatments like venetoclax are proving effective for patients with specific genetic abnormalities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in the treatment of light chain amyloidosis. Palladini, G., Milani, P.[2023]

In a study comparing two treatment regimens for AL amyloidosis, cyclophosphamide, bortezomib, and dexamethasone (CVD) showed a higher complete response rate (40.5%) compared to cyclophosphamide, thalidomide, and dexamethasone (CTD) (24.6%), indicating that CVD may be more effective in achieving deeper responses.

CVD also demonstrated superior progression-free survival (28.0 months) compared to CTD (14.0 months), suggesting that CVD may provide longer-lasting benefits for patients, although both regimens still face challenges with early mortality in AL amyloidosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A matched comparison of cyclophosphamide, bortezomib and dexamethasone (CVD) versus risk-adapted cyclophosphamide, thalidomide and dexamethasone (CTD) in AL amyloidosis. Venner, CP., Gillmore, JD., Sachchithanantham, S., et al.[2021]

In a safety run-in of the ANDROMEDA study involving 28 patients with newly diagnosed AL amyloidosis, the combination of daratumumab and CyBorD showed a high overall hematologic response rate of 96%, with 54% achieving a complete response.

The treatment was well tolerated, with minimal adverse events and no new safety concerns compared to the intravenous formulation, indicating its potential as a safe and effective option for patients with AL amyloidosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab plus CyBorD for patients with newly diagnosed AL amyloidosis: safety run-in results of ANDROMEDA. Palladini, G., Kastritis, E., Maurer, MS., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Cyclophosphamide-bortezomib-dexamethasone (CyBorD) produces rapid and complete hematologic response in patients with AL amyloidosis. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Cyclophosphamide, Bortezomib and Dexamethasone (CyBorD) for the Treatment of Newly Diagnosed AL Amyloidosis: Impact of Response on Survival Outcomes. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Advances in the treatment of light chain amyloidosis. [2023]

4. England pubmed.ncbi.nlm.nih.gov

A matched comparison of cyclophosphamide, bortezomib and dexamethasone (CVD) versus risk-adapted cyclophosphamide, thalidomide and dexamethasone (CTD) in AL amyloidosis. [2021]

5. India pubmed.ncbi.nlm.nih.gov

Cyclophosphamide, Bortezomib and Methylprednisolone (CyBorMe) for the Treatment of AL Amyloidosis: Initial Experience From a Single Center. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Daratumumab plus CyBorD for patients with newly diagnosed AL amyloidosis: safety run-in results of ANDROMEDA. [2021]

7. Japan pubmed.ncbi.nlm.nih.gov

Combined use of bortezomib, cyclophosphamide, and dexamethasone induces favorable hematological and organ responses in Japanese patients with amyloid light-chain amyloidosis: a single-institution retrospective study. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Primary treatment of light-chain amyloidosis with bortezomib, lenalidomide, and dexamethasone. [2020]

9. Japan pubmed.ncbi.nlm.nih.gov

Therapeutic outcome of cyclic VAD (vincristine, doxorubicin and dexamethasone) therapy in primary systemic AL amyloidosis patients. [2019]