REGN7257 in Adult Patients With Severe Aplastic Anemia That Is Refractory to or Relapsed on Immunosuppressive Therapy

Study Overview
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Brief Summary
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The primary objective of this study is to assess the safety and tolerability of REGN7257 in patients with immunosuppressive therapy (IST)-refractory or IST-relapsed severe aplastic anemia (SAA). An additional primary objective (for Part B only) is to evaluate the clinical efficacy of REGN7257 in patients with IST-refractory or IST-relapsed SAA. The secondary objectives of this study are to assess the following for REGN7257: Clinical response over time Maintenance of response Impact on transfusion requirements Effect on blood counts and cell populations Pharmacokinetics (PK) Immunogenicity

Official Title
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A Phase 1/2 Study of REGN7257 (Anti-Interleukin 2 Receptor Subunit Gamma [IL2RG] Monoclonal Antibody) in Patients With Severe Aplastic Anemia That Is Refractory to or Relapsed on Immunosuppressive Therapy

Conditions
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Severe Aplastic Anemia (SAA)

Intervention / Treatment
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* Drug: REGN7257


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: SAA that is IST-refractory or IST-relapsed, as defined in the protocol Hematopoietic stem cell transplantation (HSCT) is not available or suitable as a treatment option or has been refused by the patient Adequate hepatic and renal function as defined in the protocol Key Exclusion Criteria: Diagnosis of Fanconi anemia or other congenital bone marrow failure syndrome as defined in the protocol Evidence of myelodysplastic syndrome as defined in the protocol Paroxysmal nocturnal hemoglobinuria (PNH) with evidence of clinically significant hemolysis (eg, treatment indicated) or history of PNH-associated thrombosis Treatment with a T cell-depleting agent (eg, ATG or alemtuzumab) within 6 months prior to dosing Treatment with a calcineurin inhibitor (eg, cyclosporine) within 4 weeks prior to dosing as defined in the protocol Treatment with eltrombopag or investigational thrombopoietin receptor agonist, Granulocyte Colony-Stimulating Factor (G-CSF), or an androgen (eg, danazol), within 2 weeks prior to dosing HIV, hepatitis B or hepatitis C positive by serological testing at the screening visit as defined in the protocol Active tuberculosis, latent tuberculosis infection (LTBI) or history incompletely-treated tuberculosis or LTBI Active infection as defined in the protocol including COVID-19 Note: Other protocol-defined inclusion/ exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A and Part B<br>Part A: Single ascending dose Part B: Preferred dose | Drug: REGN7257<br>* Single dose will be administered by intravenous IV infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (AEs) | Part A | 12 months post-treatment, approximately 52 weeks | 
| Incidence of serious adverse events (SAEs) | Parts A and B | 12 months post-treatment, approximately 52 weeks | 
| Incidence and severity of treatment-emergent adverse events (TEAEs) up | Parts A and B | 12 months post-treatment, approximately 52 weeks | 
| Overall response rate (ORR) | Part B | 6 months post-treatment, approximately 26 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | Parts A and B | 3 months post-treatment, approximately 12 weeks | 
| Complete response (CR) | Parts A and B | 3 months post-treatment, approximately 12 weeks | 
| Partial response (PR) | Parts A and B | 3 months post-treatment, approximately 12 weeks | 
| Time to best response | Parts A and B | Up to 12 months | 
| Time to first response | Parts A and B | Up to 12 months | 
| Proportion of patients who maintain any clinical response | Parts A and B | Up to 12 months | 
| Platelet transfusions per month over time | Parts A and B | Up to 12 months | 
| Red blood cell transfusions per month over time | Parts A and B | Up to 12 months | 
| Changes in lymphocyte cell counts | Parts A and B | Up to 12 months | 
| Changes in neutrophil cell counts | Parts A and B | Up to 12 months | 
| Changes in hemoglobin cell counts | Parts A and B | Up to 12 months | 
| Changes in reticulocyte cell counts | Parts A and B | Up to 12 months | 
| Changes in platelet cell counts | Parts A and B | Up to 12 months | 
| Changes in the whole blood immune cell subsets (T cells) | Parts A and B | Up to 12 months | 
| Changes in the whole blood immune cell subsets (B cells) | Parts A and B | Up to 12 months | 
| Changes in the whole blood immune cell subsets (NK cells) | Parts A and B | Up to 12 months | 
| Drug concentrations in serum over time | Parts A and B | Up to 12 months | 
| Incidence of treatment-emergent anti-drug antibody (ADA) over time | Parts A and B | Up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Refractory, Immunosuppressive therapy (IST), Relapsed