JSP191 for Severe Combined Immunodeficiency (SCID)

Recruiting in Palo Alto (17 mi)

+10 other locations

Overseen by Theodore Moore, MD

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Waitlist Available

Sponsor: Jasper Therapeutics, Inc.

Must not be taking: Investigational agents, Chemotherapy

Disqualifiers: Acute infections, Active malignancies, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests JSP191, an antibody, in SCID patients needing a blood stem cell transplant. JSP191 helps by clearing out old blood-forming cells to make room for new, healthy ones.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are receiving other investigational agents, or concurrent biological, chemotherapy, or radiation therapy.

How is the drug JSP191 different from other treatments for SCID?

JSP191 is unique because it is a monoclonal antibody that targets CD117, a receptor on blood-forming stem cells, which helps in preparing the body for a stem cell transplant without the need for traditional chemotherapy or radiation. This approach aims to reduce the side effects associated with conventional conditioning methods used in SCID treatment. ^{1 2 3 4 5}

Research Team

Susan Prockop, MD

Principal Investigator

Boston Children's Hospital

Christen Ebens, MD

Principal Investigator

University of Minnesota

Shanmuganathan Chandrakasan, MD

Principal Investigator

Children's Healthcare of Atlanta

Michael Pulsipher, MD

Principal Investigator

Children's Hospital Los Angeles

Theodore Moore, MD

Principal Investigator

University of California, Los Angeles

Elizabeth D Hicks, M.D.

Principal Investigator

Children's National Research Institute

Rajni Agarwal-Hashmi, M.D.

Principal Investigator

Lucile Packard Children's Hospital

Christopher C. Dvorak, M.D.

Principal Investigator

UCSF Benioff's Children's Hospital

Joseph H. Oved, M.D.

Principal Investigator

Memorial Sloan Kettering Cancer Center

Sharat Chandra, M.D.

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Harry Malech, MD

Principal Investigator

National Institutes of Health Clinical Center (CC)

Eligibility Criteria

This trial is for patients with Severe Combined Immunodeficiency (SCID) who have a matching donor for blood stem cell transplantation. They must have normal organ function and typical SCID as defined by specific criteria. People with active cancer, ongoing treatments like chemotherapy or radiation, uncontrolled infections, or recent graft-versus-host disease are not eligible.

Inclusion Criteria

I have a donor who matches my HLA type.

My organs are functioning well enough for the study.

I have been diagnosed with a specific type of severe combined immunodeficiency.

Exclusion Criteria

I do not have any current severe infections.

I have had graft-versus-host disease or been on treatment for it in the last 6 months.

I am not currently on any experimental treatments or undergoing chemotherapy or radiation.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning

Participants receive a single dose of intravenous JSP191 antibody followed by monitoring for antibody clearance

4 weeks

Transplantation

Participants receive stem cell transplant and are monitored for hematopoietic recovery

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

104 weeks

Treatment Details

Interventions

• JSP191 (Monoclonal Antibodies)

Trial Overview The study is testing the safety and effectiveness of JSP191, a humanized anti-CD117 monoclonal antibody used as part of the conditioning regimen before blood stem cell transplants in SCID patients. This Phase 1/2 trial will assess how well patients tolerate this new treatment approach.

Participant Groups

Group I: Blood Stem Cell Transplant w/ anti-CD117 conditioning Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Jasper Therapeutics, Inc.

Lead Sponsor

Trials

7

Recruited

310+

Findings from Research

A 6-month-old girl with severe combined immunodeficiency (SCID) was diagnosed with compound heterozygous mutations in the JAK3 gene, which is linked to a severe form of immunodeficiency.

The patient successfully underwent bone marrow transplantation from a haploidentical donor, highlighting the potential for effective treatment in cases of JAK3-deficient SCID.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel compound heterozygous mutations in a Japanese girl with Janus kinase 3 deficiency. Sato, T., Okano, T., Tanaka-Kubota, M., et al.[2022]

In a study of 10 SCID patients with various JAK3 mutations, bone marrow transplantation effectively restored T-cell immunity, with all but one patient showing normal T-cell function after the procedure.

However, the restoration of B-cell and NK cell functions was less successful, as only 3 patients regained antibody function and only 2 showed normal NK activity post-transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Janus kinase 3 (JAK3) deficiency: clinical, immunologic, and molecular analyses of 10 patients and outcomes of stem cell transplantation. Roberts, JL., Lengi, A., Brown, SM., et al.[2022]

The patient with B-cell-negative severe combined immunodeficiency (SCID) showed a complete absence of peripheral CD3(+) T cells and CD19(+) B cells, indicating a severe impairment in the immune system.

Analysis revealed that while common gamma chain expression was normal, there was a complete arrest in the development of B cells from pro-B to pre-B stages, suggesting that genes involved in V(D)J recombination, other than RAG, may contribute to the immunodeficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complete arrest from pro- to pre-B cells in a case of B cell-negative severe combined immunodeficiency (SCID) without recombinase activating gene (RAG) mutations. Agematsu, K., Nagumo, H., Hokibara, S., et al.[2019]

Severe combined immunodeficiency (SCID) can be caused by mutations in at least seven different genes, with significant advances in understanding these causes since 1993.

Treatment options have improved dramatically, with over 95% success rates for related marrow transplants performed within the first 3.5 months of life, and recent successes in gene therapy for infants with X-linked SCID, highlighting the importance of early diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in the understanding and treatment of human severe combined immunodeficiency. Buckley, RH.[2022]

In a study of 57 SCID patients from India, most presented within 6 months of age, with common symptoms including recurrent pneumonia (66%) and failure to thrive (60%), highlighting the severe impact of this immunodeficiency.

Hematopoietic Stem Cell Transplantation (HSCT) is the only curative treatment, but outcomes were poor in the four patients who underwent the procedure, indicating a need for improved therapeutic strategies and further research into genetic causes, with 32 novel variants identified in the cohort.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical, Immunological, and Molecular Findings in 57 Patients With Severe Combined Immunodeficiency (SCID) From India. Aluri, J., Desai, M., Gupta, M., et al.[2020]

References

1. Australia pubmed.ncbi.nlm.nih.gov

Novel compound heterozygous mutations in a Japanese girl with Janus kinase 3 deficiency. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Janus kinase 3 (JAK3) deficiency: clinical, immunologic, and molecular analyses of 10 patients and outcomes of stem cell transplantation. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Complete arrest from pro- to pre-B cells in a case of B cell-negative severe combined immunodeficiency (SCID) without recombinase activating gene (RAG) mutations. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Advances in the understanding and treatment of human severe combined immunodeficiency. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical, Immunological, and Molecular Findings in 57 Patients With Severe Combined Immunodeficiency (SCID) From India. [2020]