CAEL-101 for Amyloidosis

Not currently recruiting at 330 trial locations

Overseen By Alexion Pharmaceuticals, Inc

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Alexion Pharmaceuticals

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if CAEL-101, a special antibody, can benefit individuals with AL amyloidosis. AL amyloidosis occurs when abnormal proteins accumulate in organs like the heart and kidneys, leading to serious health issues. The trial will compare CAEL-101 with a placebo to assess its impact on survival and heart-related hospital visits. Individuals with stage IIIb AL amyloidosis and heart problems who have not received previous treatments for AL amyloidosis may be suitable candidates for this trial. 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.

Will I have to stop taking my current medications?

The trial does not specify if 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 (CyBorD) before randomization.

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

Research has shown that CAEL-101, a treatment designed to clear harmful deposits in the body, is generally safe. In earlier studies, patients who used it for over 18 months did not experience organ damage and tolerated the treatment well. Another study confirmed its safety over ten years, reassuring for long-term use.

The CyBorD regimen, which includes cyclophosphamide, bortezomib, and dexamethasone, also has a strong safety record. Previous studies showed high survival rates and no new safety concerns. The combination was considered tolerable, with most side effects being manageable.

Overall, both CAEL-101 and the CyBorD regimen have demonstrated good safety in past studies, with manageable side effects and no serious organ-related problems reported. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for amyloidosis?

Unlike the standard treatments for amyloidosis, which typically involve chemotherapy regimens like CyBorD (a combination of cyclophosphamide, bortezomib, and dexamethasone), CAEL-101 works differently by targeting the amyloid deposits themselves. Researchers are excited about CAEL-101 because it is an antibody designed to bind directly to amyloid proteins, potentially clearing them from organs and tissues more effectively than current therapies. This could mean improved organ function and quality of life for patients. Additionally, CAEL-101 is administered via intravenous infusion, which might offer a new approach to tackling the disease at its core.

What evidence suggests that CAEL-101 could be an effective treatment for amyloidosis?

Research has shown that CAEL-101, a monoclonal antibody, can effectively remove harmful protein deposits from tissues and organs in people with AL amyloidosis. In this trial, participants will receive either CAEL-101 combined with standard-of-care plasma cell dyscrasia treatment or a placebo with the same standard-of-care treatment. Studies have found that CAEL-101 not only helps clear these buildups but also works faster than some current treatments. Patients who used CAEL-101 for more than 18 months tolerated it well, with no serious damage to major organs. Early results suggest that it may improve organ function, which is encouraging for those in advanced stages of the condition. Overall, CAEL-101 has the potential to improve survival rates and reduce hospital visits related to heart problems in AL amyloidosis patients. ^{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 adults with stage IIIb AL amyloidosis, a condition where abnormal proteins build up in organs. Participants must be planning their first treatment with CyBorD regimen, have measurable hematologic disease, and cardiac involvement without prior therapy for AL amyloidosis or multiple myeloma. Women of childbearing potential and men must agree to use contraception.

Inclusion Criteria

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

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

I am a man who is either surgically sterile or will use effective birth control and not donate sperm during and up to 5 or 12 months after the study, depending on my treatment.

Exclusion Criteria

I have a type of amyloidosis that is not AL amyloidosis.

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

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Primary Evaluation Treatment Period

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

18 months

Regular visits as per study protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

50 weeks

Open-Label Extension

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 regimen (cyclophosphamide, bortezomib, dexamethasone) in patients with advanced AL amyloidosis. It aims to see if CAEL-101 can improve survival by removing misfolded proteins from organs.

How Is the Trial Designed?

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

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. The study is divided into 2 parts, the Primary Evaluation Treatment period part and the Open-Label Extension period of Study.

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 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+

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

Caelum Biosciences, Inc.

Lead Sponsor

Trials

3

Recruited

430+

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

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]

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 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]

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 ...