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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04973137




Registration number
NCT04973137
Ethics application status
Date submitted
1/07/2021
Date registered
22/07/2021

Titles & IDs
Public title
A Study to Evaluate the Efficacy and Safety of Birtamimab in Mayo Stage IV Patients with AL Amyloidosis
Scientific 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
Secondary ID [1] 0 0
NEOD001-301
Universal Trial Number (UTN)
Trial acronym
AFFIRM-AL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Light Chain (AL) Amyloidosis 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Birtamimab
Other interventions - Placebo
Treatment: Drugs - Standard of Care Chemotherapy

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.

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.


Treatment: Drugs: Birtamimab
Intravenous administration of 24 mg/kg birtamimab every 28 days

Other interventions: Placebo
Intravenous 0.9% Saline administration as a placebo every 28 days

Treatment: Drugs: Standard of Care Chemotherapy
Bortezomib-containing chemotherapy regimen (e.g. cyclophosphamide, bortezomib, and dexamethasone (CyBorD)) according to the institutional standard of care
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time to all-cause mortality for the Double Blind Phase
Timepoint [1] 0 0
Time from the first dose of study drug until the pre-defined number of events (all-cause mortality) have been reached.
Secondary outcome [1] 0 0
6MWT distance for the Double Blind Phase
Timepoint [1] 0 0
Month 9
Secondary outcome [2] 0 0
Physical Component Summary score of the Short Form-36, version 2 for the Double Blind Phase
Timepoint [2] 0 0
Month 9

Eligibility
Key inclusion criteria
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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/08/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/06/2027
Actual
Sample size
Target
220
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
SESLHD: St George Hospital - Kogarah
Recruitment hospital [2] 0 0
Icon Cancer Centre - Wesley - Auchenflower
Recruitment hospital [3] 0 0
Icon Cancer Center - South Brisbane
Recruitment hospital [4] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [5] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [6] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
2217 - Kogarah
Recruitment postcode(s) [2] 0 0
4066 - Auchenflower
Recruitment postcode(s) [3] 0 0
4101 - South Brisbane
Recruitment postcode(s) [4] 0 0
5000 - Adelaide
Recruitment postcode(s) [5] 0 0
3128 - Box Hill
Recruitment postcode(s) [6] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
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California
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Connecticut
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District of Columbia
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Michigan
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Nebraska
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North Carolina
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Washington
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Wisconsin
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Austria
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Salzburg
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Vienna
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Oostende
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Izmir
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England
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Belfast

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Prothena Biosciences Ltd.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Sonia Romero
Address 0 0
Country 0 0
Phone 0 0
650-837-8550
Fax 0 0
Email 0 0
AFFIRM-ALClinicalTrial@prothena.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04973137