JSP191 Antibody Targeting Conditioning in SCID Patients

• ClinicalTrials.gov Identifier: NCT02963064
• Recruitment Status: Recruiting
• First Posted: November 15, 2016
• Last Update Posted: November 18, 2021
• Sponsor: Jasper Therapeutics, Inc.
• Information provided by (Responsible Party): Jasper Therapeutics, Inc.

Tracking Information

• First Submitted Date: November 2, 2016
• First Posted Date: November 15, 2016
• Last Update Posted Date: November 18, 2021
• Actual Study Start Date: March 20, 2017
• Estimated Primary Completion Date: August 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 20, 2021)

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

Original Primary Outcome Measures (submitted: November 9, 2016)

Emergent Adverse Events [Safety, and Tolerability of AMG 191 in patients with SCID] [ Time Frame: 104 weeks ]

Treatment-emergent adverse events (AEs) and serious adverse events (SAEs) will be assessed. Patient assessments will include alterations in vital signs, changes in physical exam, and clinical laboratory studies. Patients will be monitored for myelosuppression and anti-AMG 191 antibodies.

• Current Secondary Outcome Measures: Not Provided

Original Secondary Outcome Measures (submitted: November 9, 2016)

• Incidence and severity of acute and chronic GVHD [ Time Frame: Through study completion, about 104 weeks ]
  Evaluation of clinical symptoms, patient questionnaire, Lansky/Karnofsky scale, and clinician assessment.
• Hematopoietic recovery following HSC transplantation [ Time Frame: Through study completion, about 104 weeks ]
  Hematopoietic recovery will be evaluated by measurement of blood parameters including total WBC, hemoglobin, hematocrit, and platelet count.
• Dose of AMG 191 that achieves adequate donor HSC engraftment at 24 weeks [ Time Frame: Through study completion, about 104 weeks ]
  Myeloid chimerism is measured by isolation of CD15+ from peripheral blood mononuclear cells (PBMC) and STR analysis of the CD15+ cells.
• AMG 191 Pharmacokinetic Outcome [ Time Frame: Depending on dose received, up to 20 days ]
  Parameters will be estimated using standard population methodologies and non-linear mixed effect modeling. The influence of patient-specific clinical covariates on drug clearance will be investigated, including patient demographics and laboratory biochemistries.
• AMG 191 Pharmacodynamic Outcome [ Time Frame: Depending on dose received, up to 20 days ]
  Exploratory PK-PD analyses to investigate and identify the relationship between drug exposure and clinical endpoints for both safety and efficacy will be performed.
• Evaluation of quantitative immune recovery follow CD34 CD90 transplantation [ Time Frame: Through study completion, about 104 weeks ]
  T, B, and NK cell will be measured by CBC differential studies and flow cytometry and values will be compared to CD34 enriched HSPC.

• Current Other Pre-specified Outcome Measures: Not Provided

Original Other Pre-specified Outcome Measures (submitted: November 9, 2016)

• Determine if donor myeloid chimerism at 4 weeks predicts donor HSC engraftment at 24 weeks post-transplant [ Time Frame: Through study completion, about 104 weeks ]
  Blood myeloid chimerism measured by STR analysis of CD15+ at 4 weeks post-transplant will be compared to values obtained from the same patient at 24 weeks post-transplant.
• Determine if SCID phenotype influences response to conditioning with AMG 191 and resultant donor HSC engraftment [ Time Frame: Through study completion, about 104 weeks ]
  Blood myeloid chimerism at 24 weeks will be compared across the different SCID phenotypes.
• Compare B and T cell repertoires in SCID patients transplanted with CD34 enriched HSC versus CD34+CD90+ HSC [ Time Frame: Through study completion, about 104 weeks ]
  Diversity of the T and B cell repertoire will be assessed by parallel high throughput sequencing of the TCR beta chain and immunoglobulin heavy chain gene, respectively.
• Determine if HSC engraftment is associated with improved quality of life in patients of prior HSC transplantation. [ Time Frame: Through study completion, about 104 weeks ]
  Patients or patient surrogates in Groups A and B will be asked to complete QoL surveys in the pre- and post-transplant setting and results will be compared.

Descriptive Information

• Brief Title: JSP191 Antibody Targeting Conditioning in SCID Patients
• Official Title: 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
• Brief Summary: 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

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.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: SCID

Intervention

Biological: Humanized anti-CD117 Monoclonal Antibody (JSP191)

Procedure: single intravenous infusion of JSP191 antibody

Study Arms

Experimental: Blood Stem Cell Transplant w/ anti-CD117 conditioning

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.

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 20, 2021): 40
• Original Estimated Enrollment (submitted: November 9, 2016): 90
• Estimated Study Completion Date: August 2027
• Estimated Primary Completion Date: August 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

All patient groups must have:

1. Typical SCID as defined by Primary Immune Deficiency Treatment Consortia including but not limited to the following subtypes:

   1. T-, B+, NK-: IL-2Rcγ deficient, JAK3-deficient
   2. T-, B-, NK+: RAG1/2 deficient, Artemis-deficient
   3. 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.
2. Patients with human leukocyte antigen (HLA) matched related or unrelated donors
3. Adequate end organ function as defined in study protocol

Key Exclusion Criteria:

1. Patients with any acute or uncontrolled infections
2. Patients receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy
3. Patients with active malignancies
4. Active GVHD within 6 months prior to enrollment, or on immunosuppressive therapy for GVHD

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 3 Months and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Clinical Trials Jasper Therapeutics, Inc.; 650-549-1270; ClinicalTrials@JasperTherapeutics.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02963064
• Other Study ID Numbers: JAS-BMT-CP-001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: Data collected is for future publication

• Current Responsible Party: Jasper Therapeutics, Inc.
• Original Responsible Party: Judith Anne Shizuru, Stanford University, Professor of Medicine (Blood and Marrow Transplantation)
• Current Study Sponsor: Jasper Therapeutics, Inc.
• Original Study Sponsor: Stanford University
• Collaborators: Not Provided

Investigators

• Principal Investigator: Rajni A. Agarwal-Hashmi, M.D.; Lucile Packard Children's Hospital
• Principal Investigator: Christopher C. Dvorak, M.D.; UCSF Benioff's Children's Hospital
• Principal Investigator: Joseph H. Oved, M.D.; Memorial Sloan Kettering Cancer Center
• Principal Investigator: Theodore B. Moore, M.D.; UCLA Mattel Children's Hospital
• Principal Investigator: Sharat Chandra, M.D.; Children's Hospital Medical Center, Cincinnati
• Principal Investigator: Christen L Ebens, M.D., MPH; University of Minnesota
• Principal Investigator: Harry L Malech, M.D.; National Institutes of Health Clinical Center (CC)
• Principal Investigator: Shanmuganathan Chandrakasan, M.D.; Children's Healthcare of Atlanta

• PRS Account: Jasper Therapeutics, Inc.
• Verification Date: November 2021