A Study to Evaluate the Efficacy and Safety of Birtamimab in Mayo Stage IV Patients With AL Amyloidosis (AFFIRM-AL)
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| ClinicalTrials.gov Identifier: NCT04973137 |
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Recruitment Status :
Recruiting
First Posted : July 22, 2021
Last Update Posted : April 16, 2024
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Light Chain (AL) Amyloidosis | Drug: Birtamimab Other: Placebo Drug: Standard of Care Chemotherapy | Phase 3 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 220 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 2025 |
| Estimated Study Completion Date : | June 2027 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Birtamimab plus Standard of Care Chemotherapy- For Double-blind Phase and OLE Phase of study
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. 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. |
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 |
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Placebo Comparator: Placebo plus Standard of Care Chemotherapy- For Double-blind Phase of study
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 |
- Time to all-cause mortality for the Double Blind Phase [ 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.
- 6MWT distance for the Double Blind Phase [ Time Frame: Month 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 Phase [ Time Frame: Month 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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Key Inclusion Criteria for Double-blind Phase:
- 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
Inclusion Criteria for Open-label (OLE) Phase:
- Must not have discontinued treatment in Double-blind Phase
- WOCBP must have a negative pregnancy test and must agree to use highly effective contraception through 90 days following last study drug administration
- Male subjects must be surgically sterile or agree to use highly effective contraception through 90 days following last study drug administration
- Ability to understand and willingness to sign an ICF prior to initiating the OLE Phase
Key Exclusion Criteria for Double-blind Phase:
- 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
Exclusion Criteria for OLE Phase:
- Any medical condition or clinically significant abnormality on physical, neurological, laboratory, vital signs, or ECG examination that precludes treatment with birtamimab or participation in the study, in the medical judgment of the Investigator
- Symptomatic orthostatic hypotension that in the medical judgment of the Investigator would interfere with subject's ability to safely receive treatment or complete study assessments
- History of Grade ≥3 infusion-related AEs during the Double-blind Phase or hypersensitivity to birtamimab
- Unable or unwilling to adhere to the study-specified procedures and restrictions
- Planning to use any other investigational treatment during the study
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
| Contact: Sonia Romero | 650-837-8550 | AFFIRM-ALClinicalTrial@prothena.com | |
| Contact: Karen Lai | 650-837-8550 | AFFIRM-ALClinicalTrial@prothena.com |
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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: | April 16, 2024 |
| Last Verified: | April 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Light Chain (AL) Amyloidosis Mayo Stage IV birtamimab |
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Amyloidosis Proteostasis Deficiencies Metabolic Diseases |