JSP191 for Severe Combined Immunodeficiency (SCID)
Recruiting in Palo Alto (17 mi)
+10 other locations
Age: < 18
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Jasper Therapeutics, Inc.
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.
12345Eligibility 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.
I have been diagnosed with a specific type of severe combined immunodeficiency.
Exclusion Criteria
I do not have any current severe infections.
I am not currently on any experimental treatments or undergoing chemotherapy or radiation.
I currently have an active cancer.
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: Blood Stem Cell Transplant w/ anti-CD117 conditioningExperimental Treatment1 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.
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Children's Hospital of Los AngelesLos Angeles, CA
Children's National Medical CenterWashington, United States
Cincinnati Children's Hospital Medical CenterCincinnati, OH
Children's Healthcare of AtlantaAtlanta, GA
More Trial Locations
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Who is running the clinical trial?
Jasper Therapeutics, Inc.Lead Sponsor
References
Novel compound heterozygous mutations in a Japanese girl with Janus kinase 3 deficiency. [2022]Severe combined immunodeficiency (SCID) is the most severe form of primary immunodeficiency disease, and it is characterized by marked impairment in cellular and humoral immunity. Mutations in several genes cause SCID, one of which is Janus kinase 3 (JAK3), resulting in autosomal recessive T(-)B(+)NK(-) SCID. Only three patients with JAK3-deficient SCID have been reported in Japan. We herein describe the case of a 6-month-old girl with pneumocystis pneumonia, who was diagnosed with SCID with compound heterozygous JAK3 mutations (c.1568G>A + c.421-10G>A). One of the mutations was previously reported in another Japanese patient. The other mutation was a novel and de novo relatively deep intronic mutation causing aberrant RNA splicing. The patient was successfully treated with bone marrow transplantation from a haploidentical donor.
Janus kinase 3 (JAK3) deficiency: clinical, immunologic, and molecular analyses of 10 patients and outcomes of stem cell transplantation. [2022]We found 10 individuals from 7 unrelated families among 170 severe combined immunodeficiency (SCID) patients who exhibited 9 different Janus kinase 3 (JAK3) mutations. These included 3 missense and 2 nonsense mutations, 1 insertion, and 3 deletions. With the exception of 1 individual with persistence of transplacentally transferred maternal lymphocytes, all infants presented with a T-B+NK- phenotype. The patient mutations all resulted in abnormal B-cell Janus kinase 3 (JAK3)-dependent interleukin-2 (IL-2)-induced signal transducer and activator of transcription-5 (STAT5) phosphorylation. Additional analyses of mutations permitting protein expression revealed the N-terminal JH7 (del58A) and JH6 (D169E) domain mutations each inhibited receptor binding and catalytic activity, whereas the G589S JH2 mutation abrogated kinase activity but did not affect c association. Nine of the 10 patients are currently alive from between 4 years and 18 years following stem cell transplantation, with all exhibiting normal T-cell function. Reconstitution of antibody function was noted in only 3 patients. Natural killer (NK) function was severely depressed at presentation in the 4 patients studied, whereas after transplantation the only individuals with normal NK lytic activity were patients 1 and 5. Hence, bone marrow transplantation is an effective means for reconstitution of T-cell immunity in this defect but is less successful for restoration of B-cell and NK cell functions.
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]The B-cell lineage in a patient with B-cell-negative severe combined immunodeficiency (SCID) was analysed by using antisurrogate light chain (SL) MoAbs. Peripheral CD3(+) T cells and CD19(+) B cells were absent in the patient. The common gamma (gamma c) chain was expressed normally on the patient's peripheral NK cells and his peripheral mononuclear cells did not possess any mutations in recombinase activating gene (RAG)-1, 2. Normal levels of expression of Ku70 and Ku80 protein were found by Western blot analysis. The patient did, however, display an increase in fibroblast sensitivity to irradiation. Furthermore, flow cytometric analyses of bone marrow cells showed that surface IgM and cytoplasmic mu positive cells were absent and that CD19(+) B cells were composed of only CD34(+) terminal deoxynucleotidyl transferase (TdT)(+) SL(+) pro-B cells. The complete arrest of pro- to pre-B cell development in the SCID patient's bone marrow suggests that some genes involved in V(D)J recombination, excepting the RAG gene, may play a causative role in the immunodeficiency.
Advances in the understanding and treatment of human severe combined immunodeficiency. [2022]Human severe combined immunodeficiency (SCID) can result from mutations in any one of at least seven different genes, including those for adenosine deaminase, the common cytokine receptor gamma chain, Janus kinase 3, IL-7 receptor alpha chain, recombinase activation genes 1 and 2, and CD45. Except for adenosine deaminase, knowledge concerning the latter causes of human SCID has accrued since 1993. Advances in the treatment of this syndrome have been no less significant. Since 1982 it has been possible, by rigorous depletion of T cells from the donor marrow, to use related marrow donors other than HLA-identical siblings for successful treatment of infants with this condition. The success rate with the latter type of transplant exceeds 95% if a transplant can be performed within the first 3.5 mo of life, making early diagnosis crucial. Recently, gene therapy has also been successful in infants with X-linked SCID.
Clinical, Immunological, and Molecular Findings in 57 Patients With Severe Combined Immunodeficiency (SCID) From India. [2020]Severe combined immunodeficiency (SCID) represents one of the most severe forms of primary immunodeficiency (PID) disorders characterized by impaired cellular and humoral immune responses. Here, we report the clinical, immunological, and molecular findings in 57 patients diagnosed with SCID from India. Majority of our patients (89%) presented within 6 months of age. The most common clinical manifestations observed were recurrent pneumonia (66%), failure to thrive (60%), chronic diarrhea (35%), gastrointestinal infection (21%), and oral candidiasis (21%). Hematopoietic Stem Cell Transplantation (HSCT) is the only curative therapy available for treating these patients. Four patients underwent HSCT in our cohort but had a poor survival outcome. Lymphopenia (absolute lymphocyte counts/μL <2,500) was noted in 63% of the patients. Based on immunophenotypic pattern, majority of the cases were T-B- SCID (39%) followed by T-B+ SCID (28%). MHC class II deficiency accounted for 10.5% of our patient group. A total of 49 patients were molecularly characterized in this study and 32 novel variants were identified in our cohort. The spectrum of genetic defects in our cohort revealed a wide genetic heterogeneity with the major genetic cause being RAG1/2 gene defect (n = 12) followed by IL2RG (n = 9) and JAK3 defects (n = 9). Rare forms of SCID like Purine nucleoside phosphorylase (PNP) deficiency, reticular dysgenesis, DNA-Protein Kinase (DNA-PKcs) deficiency, six cases of MHC class II deficiency and two ZAP70 deficiency were also identified in our cohort. Fourteen percent of the defects still remained uncharacterized despite the application of next generation sequencing. With the exception of MHC class II deficiency and ZAP70 deficiency, all SCID patients had extremely low T cell receptor excision (TRECs) (<18 copies/μL).