CAEL-101 for Amyloidosis

Recruiting at 317 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

125 Participants Needed

Trial Summary

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.

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, as well as being well tolerated with few side effects. ^{1 2 3 4 5}

Is CAEL-101 safe for humans?

The safety data for CAEL-101 specifically is not available, but the CyBorD regimen, which includes some of the same components, is generally well tolerated in patients with AL amyloidosis, with few side effects reported. ^{1 2 3 6 7}

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

CAEL-101 is unique because it is an antibody-based treatment specifically targeting amyloid deposits, which is different from the CyBorD regimen that uses chemotherapy drugs like cyclophosphamide, bortezomib, and dexamethasone to target the underlying plasma cell disorder in AL amyloidosis. ^{1 2 3 8 9}

What is the purpose of this trial?

AL (or light chain) amyloidosis begins in the bone marrow where abnormal proteins misfold and create free light chains that cannot be broken down. These free light chains bind together to form amyloid fibrils that build up in the extracellular space of organs, affecting the kidneys, heart, liver, spleen, nervous system and digestive tract. 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 overall survival, reduces cardiovascular related hospitalizations and it is safe and well tolerated in patients with stage IIIb AL amyloidosis.

Research Team

Scott Swenson, MD

Principal Investigator

Alexion, AstraZeneca Rare Disease

Eligibility Criteria

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

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

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 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.

Participant Groups

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

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

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

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

3. India pubmed.ncbi.nlm.nih.gov

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

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

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

5. 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]

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]