JSP191 Antibody Targeting Conditioning in SCID Patients

Study Overview
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Brief Summary
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A Phase 1/2 study to evaluate the safety, tolerability, and efficacy of an antibody conditioning regimen, known as JSP191, in patients with Severe Combined Immune Deficiency undergoing blood stem cell transplantation

Detailed Description
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A Phase 1/2 study to evaluate the safety, tolerability, and efficacy of an antibody conditioning regimen, known as JSP191, in patients with SCID undergoing blood stem cell transplantation. Blood Stem Cell transplantation offers the only potentially curative therapy for SCID. The biological conditioning regimen, JSP191, is an antibody that binds to CD117. CD117 is the receptor for Stem Cell Factor on blood forming cells. CD117 binding to Stem Cell Factor is critical for survival and maintenance of blood forming stem cells. The binding of JSP191 to CD117 blocks CD117 from binding to Stem Cell Factor on blood forming stem cells. In the absence of CD117/Stem Cell Factor binding, hematopoietic stem cells that are currently occupying the bone marrow niches in SCID patients are depleted.

Official Title
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A Phase 1/2 Study to Evaluate the Safety, Tolerability, and Efficacy of JSP191 for Hematopoietic Cell Transplantation Conditioning to Achieve Engraftment and Immune Reconstitution in Subjects With SCID

Conditions
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SCID

Intervention / Treatment
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* Biological: Humanized anti-CD117 Monoclonal Antibody (JSP191)


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: All patient groups must have: Typical SCID as defined by Primary Immune Deficiency Treatment Consortia including but not limited to the following subtypes: T-, B+, NK-: IL-2Rcγ deficient, JAK3-deficient T-, B-, NK+: RAG1/2 deficient, Artemis-deficient T-, B+, NK+: IL7Rα deficient, CD3 subunit deficient, CD45 deficient OR Variant SCID with absent or low T cell function, Omenn syndrome, Leaky SCID, Reticular dysgenesis, Adenosine deaminase deficiency, and Purine nucleoside phosphorylase deficiency may be included after consultation with the medical monitor. Patients with human leukocyte antigen (HLA) matched related or unrelated donors Adequate end organ function as defined in study protocol Key Exclusion Criteria: Patients with any acute or uncontrolled infections Patients receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy Patients with active malignancies Active GVHD within 6 months prior to enrollment, or on immunosuppressive therapy for GVHD

Ages Eligible for Study
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Minimum Age: 3 Months

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Blood Stem Cell Transplant w/ anti-CD117 conditioning<br>The study will enroll two groups: Group A: previously transplanted SCID patients; Group B: newly diagnosed SCID. The study plans to assess JSP191 in different dose cohorts. Patients will receive a single dose of intravenous JSP191 antibody followed by monitoring for antibody clearance. Once the antibody has cleared below a certain level, patients will receive stem cell transplant and be monitored for hematopoietic recovery. | Biological: Humanized anti-CD117 Monoclonal Antibody (JSP191)<br>* Procedure: single intravenous infusion of JSP191 antibody<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1: Safety and tolerability of JSP191 as conditioning therapy in SCID patients undergoing HCT: adverse events | The number of subjects experiencing dose limiting toxicities including adverse events and serious adverse events will be assessed. | Up to 5 years post Donor Cell Transplant (28 days dose limiting toxicity period) | 
| Phase 2: Efficacy of JSP191 as conditioning therapy in SCID patients | To enable engraftment of allogeneic CD34+ hematopoietic cells, as determined by CD15+ donor myeloid chimerism | Up to 24 weeks post Donor Cell Transplant | 
| Phase 2: Efficacy of JSP191 as conditioning therapy in SCID patients | To enable immune reconstitution, as determined by the production of naive T cells | Weeks 36-104 post Donor Cell Transplant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunodeficiency, Pediatric, SCID, Bone Marrow Transplantation, GVHD, Stem Cells, Chimerism, Transplant, BMT