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A Study to Evaluate the Efficacy and Safety of Birtamimab in Mayo Stage IV Patients With AL Amyloidosis (AFFIRM-AL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04973137
Recruitment Status : Recruiting
First Posted : July 22, 2021
Last Update Posted : March 6, 2023
Sponsor:
Information provided by (Responsible Party):
Prothena Biosciences Ltd.

Study Description
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Brief Summary:
A Phase 3 study to evaluate the efficacy and safety of birtamimab plus standard of care compared to placebo plus standard of care in Mayo Stage IV patients with AL amyloidosis.

Condition or disease Intervention/treatment Phase
Light Chain (AL) Amyloidosis Drug: Birtamimab Other: Placebo Drug: Standard of Care Chemotherapy Phase 3

Detailed Description:

This is a Phase 3 multicenter, global, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of birtamimab in Mayo Stage IV patients with AL amyloidosis. The primary objective is to evaluate the efficacy of birtamimab by assessing time to all-cause mortality. All patients will receive bortezomib-containing chemotherapy regimen as standard of care.

Approximately 150 newly diagnosed Mayo Stage IV patients with AL amyloidosis will be enrolled and randomized in a 2:1 ratio to birtamimab or placebo. Subjects will remain on study until study completion, when the pre-defined number of events (all-cause mortality) have been reached.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Multicenter, Double-Blind, Placebo-Controlled, Efficacy and Safety Study of Birtamimab Plus Standard of Care vs. Placebo Plus Standard of Care in Mayo Stage IV Subjects With Light Chain (AL) Amyloidosis
Actual Study Start Date : August 30, 2021
Estimated Primary Completion Date : June 2024
Estimated Study Completion Date : June 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Amyloidosis

Arms and Interventions
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Arm Intervention/treatment
Experimental: Birtamimab plus Standard of Care Chemotherapy

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. Initiation of daratumumab at randomization allowed at the discretion of the investigator

 Drug: Birtamimab
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
Placebo Comparator: Placebo plus Standard of Care Chemotherapy

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

 Other: Placebo
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


Outcome Measures
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Primary Outcome Measures :
  1. Time to all-cause mortality [ Time Frame: Time from the first dose of study drug until the pre-defined number of events (all-cause mortality) have been reached. ]
    Comparison of time to all-cause mortality for birtamimab and placebo control.


Secondary Outcome Measures :
  1. 6MWT distance [ Time Frame: Month 9 ]
    Change from baseline to Month 9 in the 6-Minute Walk Test (6MWT) distance

  2. Physical Component Summary (PCS) score of the Short Form-36, version 2 (SF-36v2) [ Time Frame: Month 9 ]
    The Short Form-36, version 2 (SF-36v2) is a 36-item self-administered quality-of-life (QoL) questionnaire that measures health on functional status, well-being, and overall evaluation of health. Higher SF-36 scores represent better health. The Physical Component Summary (PCS) is derived primarily from questions regarding physical functioning, physical problems, bodily pain, and general health questions


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Aged ≥18 years and legal age of consent according to local regulations
  • Newly diagnosed and AL amyloidosis treatment-naïve with cardiac involvement
  • Confirmed diagnosis of AL amyloidosis
  • 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.

Key Exclusion Criteria:

  • Non-AL amyloidosis.
  • NT-proBNP >8500 pg/mL.
  • Meets the International Myeloma Working Group (IMWG) definition of multiple myeloma except for malignancy biomarker of involved/uninvolved serum free light chain ratio ≥100
  • Subject is eligible for and plans to undergo ASCT or organ transplant during the study.
  • Myocardial infarction, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or ECG evidence of acute ischemia, within 6 months prior to the Month 1-Day 1 Visit.
  • Severe valvular stenosis (e.g., aortic or mitral stenosis with a valve area <1.0 cm2) or severe congenital heart disease.
  • ECG evidence of acute ischemia or active conduction system abnormalities
  • Prior treatment with hematopoietic growth factors, transfusions of blood or blood products within 1 week of Month 1-Day 1.
  • Prior radiotherapy within 4 weeks of Month 1-Day 1.
  • Prior treatment with plasma cell-directed chemotherapy, birtamimab, daratumumab, 11- 1F4, anti-serum amyloid P antibody, doxycycline for amyloid, or other investigational treatment directed at amyloid .
  • Waldenström's macroglobulinemia and/or immunoglobulin M monoclonal gammopathy
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04973137


Contacts
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Contact: Sonia Romero 650-837-8550 AFFIRM-ALClinicalTrial@prothena.com
Contact: Christie Nie 650-837-8550 AFFIRM-ALClinicalTrial@prothena.com

Locations
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Sponsors and Collaborators
Prothena Biosciences Ltd.
More Information
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Responsible Party: Prothena Biosciences Ltd.
ClinicalTrials.gov Identifier: NCT04973137    
Other Study ID Numbers: NEOD001-301
First Posted: July 22, 2021    Key Record Dates
Last Update Posted: March 6, 2023
Last Verified: March 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Prothena Biosciences Ltd.:
Light Chain (AL) Amyloidosis
Mayo Stage IV
birtamimab
Additional relevant MeSH terms:
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Amyloidosis
Proteostasis Deficiencies
Metabolic Diseases