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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.

Tracking Information
First Submitted Date  ICMJE July 1, 2021
First Posted Date  ICMJE July 22, 2021
Last Update Posted Date March 6, 2023
Actual Study Start Date  ICMJE August 30, 2021
Estimated Primary Completion Date June 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 15, 2022)		 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.
Original Primary Outcome Measures  ICMJE
 (submitted: July 21, 2021)		 Time to all-cause mortality [ Time Frame: Time from the first dose of study drug until death or end of study over 9 months ]
Comparison of time to all-cause mortality for birtamimab and placebo control.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 2, 2023)
  • 6MWT distance [ Time Frame: Month 9 ]
    Change from baseline to Month 9 in the 6-Minute Walk Test (6MWT) distance
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: July 21, 2021)
  • Physical Component Summary (PCS) score of the 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
  • 6MWT distance [ Time Frame: Month 9 ]
    Change from baseline to Month 9 in the 6-Minute Walk Test (6MWT) distance
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate the Efficacy and Safety of Birtamimab in Mayo Stage IV Patients With AL Amyloidosis
Official Title  ICMJE 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
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Light Chain (AL) Amyloidosis
Intervention  ICMJE
  • Drug: Birtamimab
    Intravenous administration of 24 mg/kg birtamimab every 28 days
  • 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
Study Arms  ICMJE
  • 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

    Interventions:
    • Drug: Birtamimab
    • Drug: Standard of Care Chemotherapy
  • 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

    Interventions:
    • Other: Placebo
    • Drug: Standard of Care Chemotherapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 21, 2021)		 150
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2024
Estimated Primary Completion Date June 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Sonia Romero 650-837-8550 AFFIRM-ALClinicalTrial@prothena.com
Contact: Christie Nie 650-837-8550 AFFIRM-ALClinicalTrial@prothena.com
Listed Location Countries  ICMJE Australia,   Canada,   Czechia,   Denmark,   France,   Germany,   Greece,   Hungary,   Ireland,   Israel,   Italy,   Japan,   Korea, Republic of,   Netherlands,   Poland,   Portugal,   Spain,   Taiwan,   Turkey,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04973137
Other Study ID Numbers  ICMJE NEOD001-301
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Prothena Biosciences Ltd.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Prothena Biosciences Ltd.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Prothena Biosciences Ltd.
Verification Date March 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP