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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Prothena Biosciences Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

13 Oct 2021 → 23 May 2025

Decision date (initial)

2024-11-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-511066-36-00

EudraCT number

2021-000037-14

ClinicalTrials.gov

NCT04973137

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

Double-blind Phase
• To evaluate the efficacy of birtamimab plus standard of care compared to placebo plus standard of care when administered intravenously in Mayo Stage IV subjects with AL amyloidosis by assessing time to all-cause mortality.

Open-label Extension Phase
• To evaluate the long-term safety of birtamimab plus standard of care in Mayo Stage IV subjects with AL amyloidosis

Secondary objectives 1

1. To evaluate birtamimab plus standard of care compared to placebo plus standard of care on the following: • Change from baseline to Month 9 in the 6-Minute Walk Test (6MWT) distance • Change from baseline to Month 9 in health-related quality of life using the Short Form-36 questionnaire Version 2 (SF-36v2)

Conditions and MedDRA coding

Light Chain (AL) Amyloidosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Aged ≥18 years and legal age of consent according to local regulations
2. Newly diagnosed and AL amyloidosis treatment naive with cardiac involvement
3. Confirmed diagnosis of AL amyloidosis
4. Confirmed Mayo Stage IV AL Amyloidosis as defined by NT-proBNP ≥ 1800 pg/mL and Troponin-T ≥0.025 ng/mL (mcg/L) or high sensitivity cardiac troponin T ≥40 ng/L and dFLC ≥18 mg/dL
5. Planned first-line chemotherapy contains bortezomib administered subcutaneously weekly

Exclusion criteria 11

1. Non-AL amyloidosis
2. Prior treatment with hematopoietic growth factors, transfusions of blood or blood products within 1 week of Month 1-Day 1
3. Prior radiotherapy within 4 weeks of Month 1-Day 1
4. 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
5. Waldenström's macroglobulinemia and/or immunoglobulin M monoclonal gammopathy
6. NT-proBNP >8500 pg/mL
7. Meets the International Myeloma Working Group (IMWG) definition of multiple myeloma, except for malignancy biomarker of involved/and uninvolved serum free light chain ratio ≥100
8. Subject is eligible for and plans to undergo ASCT or organ transplant during the study
9. 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
10. Severe valvular stenosis (e.g., aortic or mitral stenosis with a valve area <1.0 cm2) or severe congenital heart disease
11. ECG evidence of acute ischemia or active conduction system abnormalities

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Time to all-cause mortality during the Double-blind Phase

Secondary endpoints 2

1. Change from baseline to Month 9 of the Double-blind Phase in the 6MWT distance (meters)
2. Change from baseline to Month 9 of the Double-blind Phase in the Physical Component Summary (PCS) score of the SF-36v2

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Prothena Biosciences Limited

Sponsor organisation

Prothena Biosciences Limited

Address

Block C 77 Sir John Rogerson’s Quay, Grand Canal Docklands Grand Canal Docklands

City

Dublin 2

Postcode

D02 VK60

Country

Ireland

Scientific contact point

Organisation

Prothena Biosciences Limited

Contact name

Regulatory Affairs

Public contact point

Organisation

Prothena Biosciences Limited

Contact name

Regulatory Affairs

Third parties 18

Locations

15 EU/EEA countries · 57 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Documents 80 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications