A Study of Obexelimab in Patients With Warm Autoimmune Hemolytic Anemia (SApHiAre)

Sponsor

Zenas BioPharma (USA), LLC (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05786573

Collaborator

(none)

134

Enrollment

Arms

56.2

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

This study aims to examine the efficacy and safety of obexelimab in participants with Warm Autoimmune Hemolytic Anemia (wAIHA).

Condition or Disease	Intervention/Treatment	Phase
Warm Autoimmune Hemolytic Anemia	Drug: Obexelimab Drug: Obexelimab Other: Placebo	Phase 3

Detailed Description

This study consists of a 6-month open label Safety and Dose Confirmation Run-in Period (SRP), 6-month Randomized Control Period (RCP), and an additional 1-year open-label extension (OLE) period. To enter the Screening Period (Day -28 to Day -1) in the SRP or RCP, patients must have a clinical diagnosis of primary or secondary wAIHA due to an underlying autoimmune disorder, have failed at least 1 prior wAIHA treatment regimen, and have a Hgb level of ≥ 7 to < 10 g/dL with at least one sign or symptom of anemia. For the SRP only, patients with secondary wAIHA due to underlying lymphoproliferative disease may be eligible if they are receiving stable treatment.

All patients in the SRP or RCP are allowed to continue up to 2 failed wAIHA therapies throughout the 24-week study. On Day 1 of the SRP, patients receive obexelimab administered as subcutaneous (SC) injections. On Day 1 of the RCP, patients will be randomized in a ratio of 1:1 to receive either obexelimab or placebo administered as subcutaneous (SC) injections. Patients must return to the study site for the first 5 weeks and then every 2 weeks thereafter. Patients will undergo assessments for efficacy, safety, PK, PD, and immunogenicity during the 24-week SRP or RCP.

Following the 24-week SRP or RCP, patients will have the opportunity to receive obexelimab for up to 52 weeks in the Open Label Extension (OLE) Period.

Including screening and follow-up, the maximum duration of participation in this study for an individual patient is 81 weeks (i.e., 28-day screening, 24-week SRP or RCP, 52-week OLE, and an 8-week follow-up).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

134 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study With An Open Label Safety and Dose Confirmation Run-In Period, To Evaluate the Efficacy and Safety of Obexelimab in Patients With Warm Autoimmune Hemolytic Anemia (SApHiAre)

Anticipated Study Start Date :

Apr 25, 2023

Anticipated Primary Completion Date :

Dec 31, 2026

Anticipated Study Completion Date :

Dec 31, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part A: Obexelimab Obexelimab will be administered as an SC injection for 24 weeks (Safety and Dose Confirmation Run-In Period). Participants may then continue to receive Obexelimab in the Open Label Extension (OLE) Period.	Drug: Obexelimab Obexelimab is a monoclonal antibody that simultaneously binds CD19 and FcγRIIb, resulting in down regulation of B cell activity.
Experimental: Part B: Obexelimab or Placebo Obexelimab or Placebo will be administered as an SC injection for 24 weeks (Double-Blinded Period). Participants may then continue to receive Obexelimab in the Open Label Extension (OLE) Period.	Drug: Obexelimab Obexelimab is a monoclonal antibody that simultaneously binds CD19 and FcγRIIb, resulting in down regulation of B cell activity.
Placebo Comparator: Placebo Placebo administered as an SC injection.	Other: Placebo Placebo

Arm

Intervention/Treatment

Experimental: Part A: Obexelimab

Obexelimab will be administered as an SC injection for 24 weeks (Safety and Dose Confirmation Run-In Period). Participants may then continue to receive Obexelimab in the Open Label Extension (OLE) Period.

Drug: Obexelimab

Obexelimab is a monoclonal antibody that simultaneously binds CD19 and FcγRIIb, resulting in down regulation of B cell activity.

Experimental: Part B: Obexelimab or Placebo

Obexelimab or Placebo will be administered as an SC injection for 24 weeks (Double-Blinded Period). Participants may then continue to receive Obexelimab in the Open Label Extension (OLE) Period.

Drug: Obexelimab

Obexelimab is a monoclonal antibody that simultaneously binds CD19 and FcγRIIb, resulting in down regulation of B cell activity.

Placebo Comparator: Placebo

Placebo administered as an SC injection.

Other: Placebo

Placebo

Outcome Measures

Primary Outcome Measures

1. Safety and Dose Confirmation Run-in Period (SRP) [24 weeks]
Proportion of participants with hemoglobin (Hgb) ≥ 10 g/dL and ≥ 2 g/dL increase from Baseline with no use of blood transfusion or glucocorticoid (GC) rescue therapy.
2. Randomized Control Period (RCP) [24 weeks]
Proportion of participants who achieve a durable Hgb response (defined as Hgb ≥ 10 g/dL and ≥ 2 g/dL increase from Baseline on at least 3 of 4 consecutive available visits), at the earliest on or after Week 12, with no use of blood transfusion or GC rescue therapy prior to attaining durable response through Week 24.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Males and females, ≥ 18 years of age
Clinically diagnosed with wAIHA for at least 3 months and currently receiving treatment for wAIHA or have previously received treatment for wAIHA.
Diagnosis of primary or secondary wAIHA documented by a positive direct antiglobulin test specific for anti-IgG or anti-IgA.
Failed at least 1 prior wAIHA treatment regimen.
At least one sign or symptom of anemia as assessed by the investigator at screening.
Other inclusion criteria apply.

Exclusion Criteria:

Have cold antibody AIHA, cold agglutinin syndrome, mixed type (i.e., warm, and cold) AIHA, or paroxysmal cold hemoglobinuria.
Have any other associated cause of hereditary or acquired hemolytic anemia.
For the RCP only, patients with secondary wAIHA not due to autoimmune disorders, including LPDs.
Received a transfusion within 2 weeks prior to randomization.
Use of B cell-depleting, B cell-targeted, or other biologic immunomodulatory agents within the 6 months prior to randomization.
Received IV Ig or epoetin alfa within 6 weeks prior to randomization.
Receiving more than 2 concomitant medications for the treatment of wAIHA.
Other exclusion criteria apply.