The VITAL Amyloidosis Study, a Global Phase 3, Efficacy and Safety Study of NEOD001 in Patients With AL Amyloidosis

Study Overview
=================
Brief Summary
-----------------
This is a multi-center, international, randomized, double-blind, placebo-controlled, two-arm efficacy and safety study in subjects newly diagnosed with AL amyloidosis. Subjects will remain on-study until study completion, which will occur when all primary endpoint events (all-cause mortality or cardiac hospitalizations) have been reached.

Detailed Description
-----------------
This is a multi-center, international, randomized, double-blind, placebo-controlled, two-arm efficacy and safety study in subjects newly diagnosed with AL amyloidosis. Approximately 236 subjects will be enrolled in  60 centers, with approximately 118 subjects per arm. This is an event driven trial, therefore subjects will remain on-study until study completion, which will occur when all primary endpoint events (all-cause mortality or cardiac hospitalizations) have been reached. All subjects who discontinue will be followed until the last event is adjudicated. The estimated overall study duration is approximately 42 months, including the enrollment and treatment periods Study drug will be administered once every 28 days as a 60-120 minute IV infusion. First-line chemotherapy must be a bortezomib-containing regimen, with bortezomib administered weekly. The number of cycles of first-line chemotherapy that are administered are at the discretion of the Investigator, and subsequent chemotherapy regimens may be prescribed as per standard of care at the Investigator's discretion. An independent Data Monitoring Committee (DMC) will review data on a regular basis.

Official Title
-----------------
A Phase 3, Randomized, Multicenter, Double-Blind, Placebo-Controlled, 2-Arm, Efficacy and Safety Study of NEOD001 Plus Standard of Care Versus Placebo Plus Standard of Care in Subjects With Light Chain (AL) Amyloidosis

Conditions
-----------------
Primary Systemic (AL) Amyloidosis

Intervention / Treatment
-----------------
* Drug: NEOD001
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Age ≥ 18 years Newly diagnosed, AL amyloidosis treatment naïve Bone marrow consistent with plasma cell dyscrasia Confirmed diagnosis of AL amyloidosis Cardiac involvement Planned first-line chemotherapy contains a proteasome-inhibiting agent administered weekly Adequate bone marrow reserve, hepatic and renal function Key Exclusion Criteria: Non-AL amyloidosis Meets diagnostic criteria for symptomatic multiple myeloma Subject is eligible for and plans to undergo ASCT History of Grade ≥ 3 infusion-associated AEs or hypersensitivity to another monoclonal antibody, or known hypersensitivity to diphenhydramine or acetaminophen

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NEOD001<br>24 mg/kg (maximum dose of 2500 mg) of NEOD001 administered once every 28 days. | Drug: NEOD001<br>* NEOD001, is a humanized immunoglobulin G1 monoclonal antibody, which specifically targets misfolded light chain aggregates and amyloid deposits. NEOD001 is proposed for use to target the misfolded light chain protein in subjects with AL amyloidosis.<br>|
| Placebo Comparator: Placebo<br>Placebo will be administered as a 250 mL bag of normal saline once every 28 days. | Other: Placebo<br>* Placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Composite of All-cause Mortality or Cardiac Hospitalization | Time to all-cause mortality death occurring after the first infusion of study drug or cardiac hospitalization as adjudicated by the CEC occurring at least 91 days after first infusion of study drug through last subject last visit, whichever came first | Randomization until the date of death or cardiac hospitalization, up to 32 months |