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

Phase 3
Terminated
Conditions
Light Chain (AL) Amyloidosis
Interventions
Other: Placebo
Drug: Standard of Care Chemotherapy
Registration Number
NCT04973137
Lead Sponsor
Prothena Biosciences Ltd.
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 (i.e., Double-blind Phase), followed by a long-term, open-label extension (i.e., Open-label Extension \[OLE\] Phase). The primary objective of the Double-blind Phase 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.

For the Double-blind Phase of the study, approximately 220 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.

After completion of the Double-blind Phase, eligible subjects may enter the optional OLE Phase, in which all subjects will receive open-label birtamimab treatment, regardless of Double-blind Phase randomized treatment assignment. Treatment in the OLE Phase will continue for an additional 24 months or until birtamimab is commercially available in a subject's country of residence, whichever occurs first (in accordance with country-specific regulations). The primary objective of the OLE Phase is to evaluate the long-term safety of birtamimab plus standard of care in Mayo Stage IV subjects with AL amyloidosis.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
208
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Birtamimab plus Standard of Care Chemotherapy- For Double-blind Phase and OLE Phase of studyStandard of Care ChemotherapyIntravenous 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. The initiation of daratumumab treatment at randomization is allowed at the discretion of the Investigator; initiation at any other time during the Double-blind Phase is prohibited. For subjects who did not initiate daratumumab at randomization during the Double-blind Phase, daratumumab may be initiated at any time during the OLE Phase at the Investigator's discretion.
Placebo plus Standard of Care Chemotherapy- For Double-blind Phase of studyStandard of Care ChemotherapyIntravenous 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.
Placebo plus Standard of Care Chemotherapy- For Double-blind Phase of studyPlaceboIntravenous 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.
Birtamimab plus Standard of Care Chemotherapy- For Double-blind Phase and OLE Phase of studyBirtamimabIntravenous 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. The initiation of daratumumab treatment at randomization is allowed at the discretion of the Investigator; initiation at any other time during the Double-blind Phase is prohibited. For subjects who did not initiate daratumumab at randomization during the Double-blind Phase, daratumumab may be initiated at any time during the OLE Phase at the Investigator's discretion.
Primary Outcome Measures
NameTimeMethod
Time to all-cause mortality for the Double Blind PhaseTime 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
NameTimeMethod
6MWT distance for the Double Blind PhaseMonth 9

Change from baseline to Month 9 in the 6-Minute Walk Test (6MWT) distance

Physical Component Summary score of the Short Form-36, version 2 for the Double Blind PhaseMonth 9

The Short Form-36, version 2 is a 36-item self-administered quality-of-life questionnaire that measures health on functional status, well-being, and overall evaluation of health. The Physical Component Summary score ranges from 0 to 100 with higher scores indicating higher health-related quality of life. The Physical Component Summary is derived primarily from questions regarding physical functioning, physical problems, bodily pain, and general health questions.

Trial Locations

Locations (109)

Yale Cancer Center

🇺🇸

North Haven, Connecticut, United States

Smilow Cancer Hospital Care Center at Trumbull

🇺🇸

Trumbull, Connecticut, United States

MedStar Georgetown University Hospital

🇺🇸

Washington, District of Columbia, United States

Cleveland Clinic Florida

🇺🇸

Weston, Florida, United States

Johns Hopkins University

🇺🇸

Bethesda, Maryland, United States

Boston University School of Med.

🇺🇸

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

🇺🇸

Boston, Massachusetts, United States

Barbara Ann Karmanos Cancer Institute

🇺🇸

Detroit, Michigan, United States

Mayo Clinic - Rochester

🇺🇸

Rochester, Minnesota, United States

University of Nebraska Medical Center

🇺🇸

Omaha, Nebraska, United States

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Yale Cancer Center
🇺🇸North Haven, Connecticut, United States

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