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

PHASE3RECRUITING

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.

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Study details:

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.

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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

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

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

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

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

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Eligibility

Age eligible for study : 18 and older

Healthy volunteers accepted : No

Gender eligible for study: All

Things to know

Study dates

Study start: 2021-08-30

Primary completion: 2025-06-01

Study completion finish: 2027-06-01

Study type

TREATMENT

Phase

PHASE3

Trial ID

NCT04973137

Intervention or treatment

DRUG: Birtamimab

OTHER: Placebo

DRUG: Standard of Care Chemotherapy

Conditions

• Light Chain (AL) Amyloidosis

Image related to Light Chain (AL) Amyloidosis

Condition: Light Chain (AL) Amyloidosis
DRUG: Birtamimab and other drugs
Adelaide, South Australia, Australia and more
Sponsor: Prothena Biosciences Ltd.

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Find a site

Closest Location:

Royal Adelaide Hospital

Research sites nearby

Select from list below to view details:

Royal Adelaide Hospital
Adelaide, South Australia, Australia
Box Hill Hospital
Box Hill, Victoria, Australia
Royal Perth Hospital
Perth, Western Australia, Australia
SESLHD: St George Hospital
Kogarah, New South Wales, Australia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/Arm	Intervention/Treatment
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
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

Participant Group/Arm

Intervention/Treatment

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

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

What is the study measuring?

Primary outcome

Primary Outcome Measure	Primary Outcome Description	Primary Outcome Time Frame
Time to all-cause mortality for the Double Blind Phase	Comparison of time to all-cause mortality for birtamimab and placebo control.	Time from the first dose of study drug until the pre-defined number of events (all-cause mortality) have been reached.

Secondary outcome

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome Time Frame
6MWT distance for the Double Blind Phase	Change from baseline to Month 9 in the 6-Minute Walk Test (6MWT) distance	Month 9
Physical Component Summary score of the Short Form-36, version 2 for the Double Blind Phase	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.	Month 9

Frequently Asked Questions

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You may be eligible to participate in this trial based on your search.Apply for study

Are you running this trial? If you're a clinic or sponsor, you can claim this study.Claim this trial

References

Clinical Trials Gov: A Study to Evaluate the Efficacy and Safety of Birtamimab in Mayo Stage IV Patients with AL Amyloidosis