CAEL-101 for Amyloidosis

Not currently recruiting at 341 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CAEL-101 for individuals with stage IIIa AL amyloidosis, a condition where abnormal proteins accumulate in organs like the heart and kidneys. The researchers aim to determine if CAEL-101 can extend life, reduce hospital visits due to heart issues, and ensure safety. Participants will receive either the CAEL-101 treatment or a placebo, alongside standard care for their condition. Suitable candidates have stage IIIa AL amyloidosis with heart involvement and have not received prior treatment for this condition. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that CAEL-101 is generally well-tolerated by patients over long periods. In studies where patients used CAEL-101 for more than 18 months, it did not cause organ damage. Another study confirmed that CAEL-101 remained safe and well-tolerated even after 10 years. However, some sources indicate that more long-term data is needed to fully understand any potential delayed issues. Overall, based on current evidence, CAEL-101 appears safe for human use. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for amyloidosis?

Researchers are excited about CAEL-101 because it offers a unique approach to treating amyloidosis. Unlike most standard treatments that primarily focus on managing symptoms and slowing disease progression, CAEL-101 is designed to directly target and clear amyloid deposits from the organs. This new mechanism of action could potentially improve organ function and overall quality of life for patients. Additionally, CAEL-101 is administered via intravenous infusion, which allows for precise dosing and may lead to more consistent results compared to oral medications.

What evidence suggests that this trial's treatments could be effective for AL amyloidosis?

Research has shown that CAEL-101, a monoclonal antibody, may help treat AL amyloidosis by clearing harmful protein deposits from organs. Studies have found that CAEL-101 is generally well tolerated and can lead to quicker organ recovery compared to current treatments. It is considered safe, with no major harm to organs reported.

In this trial, participants will receive either CAEL-101 combined with standard-of-care (SoC) plasma cell dyscrasia treatment or a placebo combined with SoC. The CyBorD regimen, which uses a combination of drugs, is already a well-known treatment for this condition and often leads to positive blood test results for many patients. Together, CAEL-101 and CyBorD aim to help patients with AL amyloidosis live longer and reduce hospital visits for heart problems. ^{1 2 4 6 7}

Who Is on the Research Team?

Scott Swenson, MD

Principal Investigator

Alexion, AstraZeneca Rare Disease

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04504825

A Study to Evaluate the Efficacy and Safety of CAEL-101 in ... The primary purpose of this study is to determine whether CAEL-101, a monoclonal antibody that removes AL amyloid deposits from tissues and organs, improves ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/PMC10428285

S204: SAFETY AND TOLERABILITY OF CAEL-101, AN ANTI ... Currently enrolled patients have been treated for ≥18 months and CAEL-101 was generally well tolerated without evidence of organ toxicity.

3. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/540/499891/Safety-and-Tolerability-of-Cael-101-an-Anti

Safety and Tolerability of Cael-101, an Anti-Amyloid ... CAEL-101 is a novel, investigational, potentially first-in-class therapy to remove amyloid fibrils from organs. Aims: To present safety, ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0268960X2500044X

Suppression to removal, an emerging therapeutic ... Overall, CAEL-101 has demonstrated a favorable toxicity profile and improved organ responses, with faster treatment response time than current therapies in ...

5. mayo.edu mayo.edu/research/clinical-trials/cls-20513443

Clinical Trials The purpose of this study is to determine if CAEL-101 and treatment for plasma cell dyscrasia improves overall survival in Mayo stage IIIb AL ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04512235

A Study to Evaluate the Efficacy and Safety of CAEL-101 in ... The primary purpose of this study is to determine whether CAEL-101, a monoclonal antibody that removes AL amyloid deposits from tissues and organs, improves ...

7. ashpublications.org ashpublications.org/bloodadvances/article/9/19/4946/546231/Long-term-follow-up-of-patients-with-AL

Long-term follow-up of patients with AL amyloidosis treated on ... We confirm in this longitudinal study that CAEL-101 is safe and well tolerated over 10 years. Additionally, despite low cumulative dose ...