JSP191 for Chronic Granulomatous Disease

Overseen By Sandra Anaya-O'Brien, R.N.

Age: Any Age

Sex: Any

Trial Phase: Phase < 1

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Disqualifiers: Pregnant, HIV positive, Uncontrolled seizures, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether JSP191 (also known as AMG 191) can enhance the success of stem cell transplants for individuals with chronic granulomatous disease (CGD), a rare immune disorder that leads to serious infections. The trial examines if JSP191 can benefit those needing a transplant from an unrelated donor, as such transplants often involve complications. Ideal participants are individuals aged 4 to 65 years with CGD who require a transplant and lack a sibling donor. As an Early Phase 1 trial, this research aims to understand how JSP191 functions in people, offering participants the chance to be among the first to receive this potentially groundbreaking treatment.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that JSP191 is likely to be safe for humans?

Research has shown that JSP191 has been tested in patients with other conditions, such as Fanconi Anemia. In these studies, JSP191 was safe to administer, and no treatment-related side effects were reported. This suggests JSP191 might be well-tolerated in humans. However, specific safety information for individuals with chronic granulomatous disease (CGD) is not yet available. As this is an early phase trial, the primary goal is to assess the safety of JSP191 and understand how the body processes it. This phase involves careful monitoring to ensure participants' safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for Chronic Granulomatous Disease (CGD) involve bone marrow transplants or gene therapy to correct the genetic defect, which can be complex and risky. JSP191 is unique because it is a monoclonal antibody designed to target and clear defective blood-forming stem cells before a transplant, making space for healthy cells without the need for aggressive chemotherapy. Researchers are excited about JSP191 because it could offer a safer and potentially more effective conditioning regimen, reducing the side effects and risks associated with traditional treatments. This innovative approach could lead to better outcomes for CGD patients by improving the success rate of transplants.

What evidence suggests that JSP191 might be an effective treatment for chronic granulomatous disease?

Research has shown that JSP191 might enhance the success of stem cell transplants for individuals with chronic granulomatous disease (CGD). In this trial, eligible CGD patients will receive a one-time infusion of JSP191, along with Alemtuzumab and TBI, as part of the HSCT conditioning regimen. This drug aims to help the body accept new stem cells by creating a more favorable environment. Early results suggest JSP191 can improve outcomes when using stem cells from unrelated donors, which is often necessary for CGD patients. Although data remains limited, JSP191's mechanism offers hope for fewer complications during the transplant process. This could result in safer and more effective transplants for those with CGD. ^{1 2 4 6 7}

Who Is on the Research Team?

Elizabeth M Kang, M.D.

Principal Investigator

National Institute of Allergy and Infectious Diseases (NIAID)

Are You a Good Fit for This Trial?

This trial is for people aged 4-65 with Chronic Granulomatous Disease (CGD) needing a stem cell transplant and have an unrelated matched donor. Participants must be able to stay near the NIH for 3 months post-transplant, use contraception, and not have major illnesses or organ failure that could affect survival after the transplant.

Inclusion Criteria

Has an unrelated matched donor available (but no matched related donor available)

If of childbearing potential, must agree to consistently use contraception from 1 month prior to baseline, throughout study participation, and for 1 year after receiving transplanted cells. Acceptable forms of contraception are: Contraceptive pills or patch, Norplant, Depo-Provera, or other FDA-approved contraceptive method; Male partner has previously undergone a vasectomy

If able to impregnate a partner, must agree to consistently use contraception from the time of enrollment through 3 months post-transplant. Acceptable forms of contraception are: Male condom with spermicide

Exclusion Criteria

I have seizures that are not controlled by medication.

Transaminases > 5x upper limit of normal based on the individual s clinical situation and at the discretion of the investigator

CRP > 100 mg/dL within 6 weeks of the transplant

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Multiple visits for exams and tests

Conditioning

Participants undergo conditioning with JSP191, alemtuzumab, and total body irradiation to prepare for the transplant

1 week

Inpatient hospital stay

Transplant and Recovery

Participants receive a high-dose donor graft infusion followed by post-transplant cyclophosphamide

40-50 days

Inpatient hospital stay

Follow-up

Participants are monitored for safety and effectiveness after treatment, including engraftment and GvHD assessment

104 weeks

2 visits per week for 100 days, then periodic visits up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• JSP191

Trial Overview The study tests JSP191 in patients with CGD undergoing stem cell transplants from unrelated donors. It aims to improve success rates by including a conditioning phase where JSP191 is administered intravenously before the actual transplant procedure.

How Is the Trial Designed?

Group I: Single arm study Experimental Treatment 1 Intervention

Eligible CGD patients will receive one time infusion of study product along with Alemtuzumab and TBI as part of HSCT conditioning regimen

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

In a study of 12 female carriers of X-linked Granulomatous Disease (XL-CGD), it was found that 50% had skewed X-chromosome inactivation (XCI) and 65% showed misrepresentation of the wild-type gene, indicating potential immune dysfunction despite having some functional immune cells.

The research revealed that many carriers experienced immune dysregulation, characterized by changes in various immune cell populations and a correlation between residual reactive oxygen species (ROS) levels and the presence of INFγ-expressing T cells, suggesting that even carriers with some functional immune response can suffer from significant health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunological Aspects of X-Linked Chronic Granulomatous Disease Female Carriers. Chiriaco, M., Salfa, I., Ursu, GM., et al.[2021]

MOG antibodies (MOG-abs) are increasingly recognized as important biomarkers in demyelinating diseases of the central nervous system, particularly in pediatric patients, where they are associated with a variety of clinical syndromes such as acute disseminated encephalomyelitis (ADEM) and optic neuritis (ON).

The review emphasizes the need for serologic testing for MOG-abs in children, as their presence can influence long-term monitoring, treatment decisions, and patient counseling, highlighting the importance of a proposed clinical classification system for pediatric MOG antibody-associated disorders (MOGAD).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

E.U. paediatric MOG consortium consensus: Part 1 - Classification of clinical phenotypes of paediatric myelin oligodendrocyte glycoprotein antibody-associated disorders. Bruijstens, AL., Lechner, C., Flet-Berliac, L., et al.[2022]

Long-term antibiotic prophylaxis in patients with chronic granulomatous disease (CGD) significantly reduced severe bacterial infections from 4.8 to 1.6 severe infections per 100 patient months, highlighting its efficacy in managing bacterial complications.

However, the use of antibiotics was associated with an increase in fungal infections, particularly from Aspergillus species, which have become the leading cause of complications and mortality in CGD patients, indicating a need for balanced prophylactic strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up and outcome of 39 patients with chronic granulomatous disease. Liese, J., Kloos, S., Jendrossek, V., et al.[2015]

Immunization with myelin basic protein (MBP) can induce experimental allergic encephalomyelitis (EAE) in mice, serving as a model for multiple sclerosis, with specific MBP peptides like Ac1-11 and p35-47 being particularly effective.

NZW and (NZB x NZW)F1 mouse strains are susceptible to EAE induced by MBP and its peptides, demonstrating that their antigen-presenting cells can effectively present MBP to T-cells, despite genetic differences in T-cell receptor gene segments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

'Lupus-prone' mice are susceptible to organ-specific autoimmune disease, experimental allergic encephalomyelitis. Zamvil, SS., al-Sabbagh, A., Nelson, PA., et al.[2018]

In a study using F1 (SJL/J×C57BL/6) mice with MOG35-55-induced EAE, treatment with Ig-MOG led to recovery from the disease, while Ig-PLP1 treatment worsened the condition by reducing protective anti-MOG antibodies.

The exacerbation of EAE by Ig-PLP1 was linked to a specific reduction in protective IgG2a/b antibodies produced by marginal zone B cells, suggesting a regulatory mechanism that could be targeted for therapeutic strategies in autoimmune diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In trans T cell tolerance exacerbates experimental allergic encephalomyelitis by interfering with protective antibody responses. Cascio, JA., Khairallah, MT., Wan, X., et al.[2021]

In a study of 123 patients with MOG-antibody-associated disease (MOGAD), researchers identified two main immune response patterns, with one being linked to active disease characterized by strong interactions with immune receptors.

The findings suggest that targeting Fcγ receptors (FcγRs) could be a promising therapeutic strategy for MOGAD, as these receptors play a key role in the disease's pathogenicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Humoral signatures of MOG-antibody-associated disease track with age and disease activity. Spatola, M., Chuquisana, O., Jung, W., et al.[2023]

A 14-month-old boy with X-linked chronic granulomatous disease successfully underwent HLA-haploidentical stem cell transplantation, leading to normalized immune function and disease-free status for over three years without antibiotic prophylaxis.

The use of donor lymphocyte infusions helped maintain the transplant's effectiveness, suggesting that HLA-haploidentical HSCT is a viable treatment option for patients lacking matched donors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case report: HLA-haploidentical HSCT rescued with donor lymphocytes infusions in a patient with X-linked chronic granulomatous disease. Scheiermann, J., Künkele, A., von Stackelberg, A., et al.[2023]

Chronic granulomatous disease (CGD) is primarily caused by defects in the NADPH oxidase complex, leading to impaired immune function, but newer forms like NCF4/p40phox deficiency are milder and do not typically result in severe infections.

Hematopoietic stem cell transplantation (HSCT) has shown a significant improvement in survival rates for CGD patients, exceeding 84-90%, and ongoing research into gene therapy and immunomodulators offers promising future treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic Granulomatous Disease: a Comprehensive Review. Yu, HH., Yang, YH., Chiang, BL.[2021]

A case study of a boy with chronic sterile multifocal osteomyelitis and autoimmune conditions revealed that he had homozygous RAG1 mutations, indicating a genetic basis for his symptoms.

This finding expands the understanding of RAG deficiency, showing that it can lead to a combination of immunodeficiency, autoimmunity, and granulomatous disease, highlighting the complexity of immune system disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exome sequencing reveals RAG1 mutations in a child with autoimmunity and sterile chronic multifocal osteomyelitis evolving into disseminated granulomatous disease. Reiff, A., Bassuk, AG., Church, JA., et al.[2021]

The study identified the peptide pR89-101 from the C-terminal region of myelin basic protein (MBP) as a major encephalitogenic determinant in SJL/J mice, which can induce experimental allergic encephalomyelitis (EAE).

The peptide pR89-101 was shown to be highly immunogenic and equally encephalitogenic as intact MBP, indicating its potential role in triggering autoimmune responses in this mouse model.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of a major encephalitogenic T cell epitope in SJL/J mice with synthetic oligopeptides of myelin basic protein. Sakai, K., Zamvil, SS., Mitchell, DJ., et al.[2019]

In a study of 85 patients with chronic granulomatous disease (CGD), 8% were identified as having the variant type X91+, with a median age of onset at just 4 months, highlighting the early impact of this condition.

Patients with X91+ CGD showed a wide range of neutrophil function, as indicated by the stimulation index (SI), which suggests that clinical manifestations can vary significantly, and underscores the need for awareness to avoid missed diagnoses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Variant Type X91+ Chronic Granulomatous Disease: Clinical and Molecular Characterization in a Chinese Cohort. Sun, B., Zhu, Z., Hui, X., et al.[2022]

In a study of 26 boys with X-linked chronic granulomatous disease (X-CGD), haploid hematopoietic stem cell (haplo-HSC) transplantation combined with third-party umbilical cord blood (tpCB) transplantation showed promising results, with a 5-year event-free survival rate of 81% and an overall survival rate of 89%.

The treatment led to normal NADPH oxidase activity within one month post-transplantation, indicating effective restoration of immune function, and no primary implant failures were reported, highlighting the safety and efficacy of this combined transplantation approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A clinical study of haploid hematopoietic stem cells combined with third-party umbilical cord blood transplantation in the treatment of chronic granulomatous disease]. Tang, XF., Lu, W., Jing, YF., et al.[2020]

In a study of 15 patients with p22(phox)-deficient chronic granulomatous disease (CGD), the survival rate after 2 years of age was notably high at 93%, indicating a prolonged survival plateau beyond this age.

Prophylactic treatment with interferon-gamma (IFN-γ) did not significantly reduce the rate of severe infections in these patients, suggesting that its efficacy in preventing infections may be limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcome of patients with p22 (phox) -deficient chronic granulomatous disease on Jeju Island, Korea. Kang, HS., Hwang, G., Shin, KS.[2020]

A study of 75 carriers of X-linked chronic granulomatous disease (XL-CGD) revealed that they experience significantly reduced quality of life (QoL) compared to both adult CGD patients and age-matched female controls, highlighting the impact of this condition even in carriers.

Over 40% of XL-CGD carriers reported moderate to severe anxiety, which was linked to higher depression scores and lower self-esteem, indicating a need for proactive psychological assessment and management for these individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-Related Quality of Life and Emotional Health in X-Linked Carriers of Chronic Granulomatous Disease in the United Kingdom. Battersby, AC., Braggins, H., Pearce, MS., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05600907

Study to Assess the Use of JSP191 in Matched Unrelated ... This is a pilot study for individuals with chronic granulomatous disease (CGD) using an unmanipulated matched unrelated donor (MUD) graft.

2. ir.jaspertherapeutics.com ir.jaspertherapeutics.com/news-releases/news-release-details/jasper-therapeutics-announces-new-clinical-trial-national

News Release Details Jasper Therapeutics Announces New Clinical Trial with the National Institute of Allergy and Infectious Diseases to Evaluate JSP191 in Chronic ...

3. withpower.com withpower.com/trial/early-phase-1-chronic-granulomatous-disease-cgd-10-2022-8758a

JSP191 for Chronic Granulomatous Disease Objective:To see if a study drug (JSP191) can help improve the success rates of stem cell transplants for people with CGD from an unrelated donor.Eligibility: ...

4. trial.medpath.com trial.medpath.com/clinical-trial/2a79d9a3f5d1defe/pilot-study-jsp191-unrelated-donor-transplantation-cgd

Study to Assess the Use of JSP191 in Matched Unrelated ... This is a pilot study for individuals with chronic granulomatous disease (CGD) using an unmanipulated matched unrelated donor (MUD) graft. · Objectives:

5. cgtlive.com cgtlive.com/view/new-collaboration-lower-dose-gene-therapy-conditioning-sickle-cell-disease

New Collaboration to Evaluate Lower-Dose Gene Therapy ... Jasper Therapeutics and Aruvant Sciences are studying the use of JSP191 used with ARU-1801 in patients with sickle cell disease.

6. ir.jaspertherapeutics.com ir.jaspertherapeutics.com/news-releases/news-release-details/jasper-therapeutics-announces-positive-clinical-data

News Release Details The first two Fanconi Anemia patients receiving JSP191 achieved 100% donor chimerism JSP191 safe to infuse with no treatment-adverse events ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05600907?term=AREA%5BBasicSearch%5D(AREA%5BConditionSearch%5D(%22Chronic%20Granulomatous%20Disease%22))&rank=4

Study to Assess the Use of JSP191 in Matched Unrelated ... Also called a data safety and monitoring board, or DSMB. Early Phase 1 (formerly listed as Phase 0). A phase of research used to describe exploratory trials ...