JSP191 + Stem Cell Transplant for Sickle Cell Anemia

Overseen By Kelly S Norris

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Disqualifiers: ECOG status, DLCO, Oxygen saturation, others

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

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a new antibody drug, briquilimab (JSP191), can increase the success of blood stem cell transplants for people with sickle cell disease (SCD). SCD is a genetic blood disorder that can cause severe health issues and organ damage. The trial aims to improve the success rate of stem cell transplants, currently the only potential cure. People with sickle cell disease who qualify for a transplant, especially those facing serious health problems despite treatment, might be suitable candidates for this trial. Additionally, healthy family members willing to donate stem cells are needed.

As a Phase 1/Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group. Participants have the opportunity to contribute to groundbreaking advancements in SCD treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify whether participants must stop taking their current medications. However, it mentions that participants with certain complications must be on sickle cell treatment/medication, suggesting that some medications may need to be continued.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, since the trial involves a stem cell transplant, it's possible that some medications might need to be adjusted. Please consult with the trial coordinators for specific guidance.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that briquilimab, also known as JSP191, has been tested in over 145 people, including both patients and healthy volunteers. It has generally been safe and well-tolerated. Importantly, in previous studies with sickle cell disease patients, those who received briquilimab successfully completed neutrophil engraftment—an important step in the treatment process—within 12-16 days, indicating their white blood cells returned to normal. This suggests the treatment can work without causing severe side effects in these patients.

While researchers continue to study briquilimab, these findings provide some confidence in its safety for those considering joining a clinical trial. However, as with any medical treatment, discussing the risks and benefits with a healthcare provider is essential. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for sickle cell anemia?

Researchers are excited about the treatment JSP191 for sickle cell anemia because it offers a novel approach compared to current options like hydroxyurea and blood transfusions. JSP191 is unique as it is an antibody that targets a specific protein on blood stem cells, potentially making stem cell transplants safer and more effective. This treatment could reduce the need for toxic chemotherapy typically used to prepare patients for transplants. By making transplants less risky, JSP191 might expand access to this potentially curative option for more patients with sickle cell anemia.

What evidence suggests that this trial's treatments could be effective for sickle cell anemia?

Research has shown that briquilimab, also known as JSP191, could help treat sickle cell disease. In this trial, participants with sickle cell disease will receive briquilimab as part of their treatment. A previous study found that all three participants with sickle cell disease who received briquilimab successfully reached a key recovery step called neutrophil engraftment within 12 to 16 days. This finding suggests that briquilimab might improve the success of blood stem cell transplants. The treatment also appears safe and well-tolerated. These early results are promising, especially for a condition that needs better treatment options for survival. ^{1 6 7 8 9}

Who Is on the Research Team?

John F Tisdale, M.D.

Principal Investigator

National Heart, Lung, and Blood Institute (NHLBI)

Are You a Good Fit for This Trial?

This trial is for people aged 13 or older with sickle cell disease (SCD) at high risk due to organ damage or complications, and those with beta-thalassemia who have significant iron overload. Participants must be eligible for a blood stem cell transplant and have a matched family donor. They should understand the study procedures, agree to use birth control during the study, and not be pregnant or breastfeeding.

Inclusion Criteria

I am at least 4 years old, weigh 20 kg or more, and willing to donate stem cells and blood for research.

I have beta-thalassemia with moderate to severe iron overload.

Negative serum or urine beta-HCG

Exclusion Criteria

Baseline oxygen saturation of <85% or PaO2 <70

Evidence of uncontrolled bacterial, viral, or fungal infections within one month prior to starting the conditioning regimen

Left ventricular ejection fraction: <35% estimated by ECHO

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Transplant and Recovery

Participants remain in the hospital for the transplant and recovery, receiving stem cells and various drugs

4 weeks

Inpatient stay

Post-Transplant Monitoring

Participants must remain within 1 hour of the NIH for 3 months post-transplant, with clinic visits up to 2 times a week

12 weeks

Up to 2 visits per week (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including mental function tests and MRI scans

1 year

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Alemtuzumab
• Filgrastim (G-CSF)
• Hydroxyurea
• JSP191
• Plerixafor
• Sirolimus
• TBI

Trial Overview The trial tests whether adding briquilimab (JSP191), an antibody drug, improves outcomes of nonmyeloablative hematopoietic cell transplantation in treating SCD and beta-thalassemia. It involves hospitalization for about 30 days for the transplant procedure followed by close monitoring up to three months post-transplant.

How Is the Trial Designed?

Group I: briquilimab in stem cell transplant recipients for SCD Experimental Treatment 7 Interventions

Affected SCD and beta-thal subjects will receive briquilimab

Group II: Stem cell Donors of Recipients undergoing stem cell transplant Active Control 1 Intervention

Participants donate stem cells for recipient to undergo stem cell transplant

Who Is Running the Clinical Trial?

National Heart, Lung, and Blood Institute (NHLBI)

Lead Sponsor

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

In a study involving 13 high-risk adult patients with sickle cell disease, a chemotherapy-free stem cell transplantation regimen resulted in successful engraftment in all patients, with 92% maintaining stable mixed donor/recipient chimerism after a median follow-up of 22 months.

The treatment showed no mortality or graft-versus-host disease, and patients experienced significant improvements in hemoglobin levels and quality of life, including aspects like bodily pain and vitality, highlighting the efficacy and safety of this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonmyeloablative Stem Cell Transplantation with Alemtuzumab/Low-Dose Irradiation to Cure and Improve the Quality of Life of Adults with Sickle Cell Disease. Saraf, SL., Oh, AL., Patel, PR., et al.[2017]

Targeted marrow irradiation (TMI) at a dose of 8 Gy to the bone marrow and 2 Gy to the rest of the body shows promise as a safer alternative to traditional total body irradiation (TBI) for hematopoietic stem cell transplant in sickle cell disease, resulting in reduced organ damage and better donor cell engraftment.

In a preclinical study using a sickle cell mouse model, TMI led to successful long-term engraftment and significant recovery of sickle cell disease features, including improved red blood cell counts and vascular health, indicating its potential efficacy in treating this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and characterization of a preclinical total marrow irradiation conditioning-based bone marrow transplant model for sickle cell disease. Sargur Madabushi, S., Fouda, R., Ghimire, H., et al.[2022]

A multicenter pilot study involving 22 adults with severe sickle cell disease demonstrated that a reduced toxicity bone marrow transplantation (BMT) regimen is feasible and safe, achieving a 1-year overall survival rate of 91% and an event-free survival rate of 86%.

The study showed significant improvements in health-related quality of life, particularly in pain interference and physical function, indicating that BMT can enhance the quality of life for patients with severe sickle cell disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bone marrow transplantation for adolescents and young adults with sickle cell disease: Results of a prospective multicenter pilot study. Krishnamurti, L., Neuberg, DS., Sullivan, KM., et al.[2020]

A Phase II clinical trial of haploidentical bone marrow transplantation (BMT) with post-transplantation cyclophosphamide showed a 93% stable donor engraftment rate at 6 months and 100% overall survival among 15 patients, indicating high efficacy for treating severe sickle cell disease (SCD).

The addition of thiotepa to the conditioning regimen reduced the risk of graft rejection, with only 2 patients experiencing severe acute graft-versus-host disease (GVHD), suggesting that this approach minimizes transplantation-related morbidity while improving outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haploidentical Bone Marrow Transplantation with Post-Transplantation Cyclophosphamide Plus Thiotepa Improves Donor Engraftment in Patients with Sickle Cell Anemia: Results of an International Learning Collaborative. de la Fuente, J., Dhedin, N., Koyama, T., et al.[2020]

In a study of 50 adult patients with sickle cell disease referred for haploidentical hematopoietic stem cell transplantation (HSCT), only 10 patients underwent the procedure, highlighting challenges such as insurance denial and patient reluctance.

The modified Hopkins regimen used for HSCT resulted in a high engraftment rate of 87.5% and low morbidity, with 87.5% of patients alive at a median follow-up of 16 months, suggesting its potential for broader application in future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haploidentical Peripheral Blood Stem Cell Transplantation Demonstrates Stable Engraftment in Adults with Sickle Cell Disease. Saraf, SL., Oh, AL., Patel, PR., et al.[2023]

Citations

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

News Release Details All three sickle cell disease participants treated with briquilimab successfully engrafted with neutrophil engraftment within 12-16 days

2. ir.jaspertherapeutics.com ir.jaspertherapeutics.com/news-releases/news-release-details/new-positive-data-presented-briquilimab-conditioning-patients

New Positive Data Presented on Briquilimab Conditioning ... Data from the study show that briquilimab infusion has a promising safety profile and appears to be well tolerated in patients with FA.

3. researchgate.net researchgate.net/publication/352077791_Early_results_of_phase_1_study_of_JSP191_an_anti-CD117_monoclonal_antibody_with_non-myeloablative_conditioning_in_older_adults_with_MRD-positive_MDSAML_undergoing_allogeneic_hematopoietic_cell_transpl

Early results of phase 1 study of JSP191, an anti-CD117 ... Early results of phase 1 study of JSP191, an anti-CD117 monoclonal antibody, with non-myeloablative conditioning in older adults with MRD-positive MDS/AML ...

4. ctv.veeva.com ctv.veeva.com/study/addition-of-jsp191-c-kit-antibody-to-nonmyeloablative-hematopoietic-cell-transplantation-for-sickl

Addition of JSP191 (C-kit Antibody) to Nonmyeloablative ... Follow trial. Addition of JSP191 (C-kit Antibody) to Nonmyeloablative Hematopoietic Cell Transplantation for Sickle Cell Disease and Beta-Thalassemia.

5. finance.yahoo.com finance.yahoo.com/news/jasper-therapeutics-announces-positive-clinical-130000277.html

Jasper Therapeutics Announces Positive Clinical Data ... All three sickle cell disease participants treated with briquilimab successfully engrafted with neutrophil engraftment within 12-16 days.

6. firstwordpharma.com firstwordpharma.com/story/5707320

Jasper Therapeutics Announces Positive Follow-up ... First two sickle cell disease participants have achieved 100% donor myeloid chimerism through 100 days follow-up; Third sickle cell disease ...

7. ir.jaspertx.com ir.jaspertx.com/news-releases/news-release-details/jasper-therapeutics-announces-health-canada-clearance-clinical

News Release Details To date, briquilimab has a demonstrated efficacy and safety profile in more than 145 dosed participants and healthy volunteers, with clinical ...

8. sec.gov sec.gov/Archives/edgar/data/1788028/000121390023066233/ea183229ex99-1_jasperthera.htm

Jasper Therapeutics Reports Second Quarter 2023 ... To date, briquilimab has a demonstrated efficacy and safety profile in over 130 dosed subjects and healthy volunteers, with clinical outcomes as ...

9. biospace.com biospace.com/jasper-therapeutics-announces-data-from-first-transplant-naive-patient-in-phase-1-clinical-trial-of-jsp191-as-conditioning-agent-in-patients-with-scid-undergoing-hematopoietic-cell-transplantation

Jasper Therapeutics Announces Data from First ... Preclinical studies have shown that JSP191 as a single agent safely depletes normal and diseased hematopoietic stem cells, including in animal ...