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Sickle Cell AnemiaPhase 1/2NCT05357482

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

A Phase 1/2 study testing TBI, Hydroxyurea and briquilimab in people with Sickle Cell Anemia and Beta Thalassemia, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

Background: Sickle cell disease (SCD) is an inherited disorder of the blood. It can damage a person s organs and cause serious illness and death. A blood stem cell transplant is the only potential cure for SCD. Treatments that improve survival rates are needed. Read more about this study

Who is it for?
Ages 4 to 100 years
Conditions the study is for
Sickle Cell Anemia, Beta Thalassemia
What is being tested?
TBI, Hydroxyurea and briquilimab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
1 siteUnited States
Study dates
12 May 2022to 31 Jan 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 4 to 100 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Recipient: patients must fulfill one disease category (criteria 1) and all of criteria 2
  • 1. Patients with sickle cell disease at high risk for disease related morbidity or mortality, defined by having an end-organ damage (A, B, C, D, or E) or complication(s) not ameliorated by SICKLE CELL-SPECIFC THERAPIES (F):
  • Stroke defined as a clinically significant neurologic event that is accompanied by an infarct on cerebral MRI OR an abnormal trans-cranial Doppler examination (>=200 cm/s); OR
  • Sickle cell related renal insufficiency defined by a creatinine level >=1.5 times the upper limit of normal (see table below) and kidney biopsy consistent with sickle cell nephropathy OR nephrotic syndrome OR creatinine clearance <60mL/min/1.73m2 for patients <16 years of age or <50mL/min for patients >16 years of age OR requiring peritoneal or hemodialysis. OR
  • Age (Years) Upper limit of normal serum creatinine (mg/dl)
  • <= 5 0.8
Show all 35Show fewer
  • 5 < age <= 10 1.0
  • 10 < age <= 15 1.2
  • > 15 1.3
  • Tricuspid regurgitant jet velocity (TRV) of >=2.5 m/s in patients at least 3 weeks after a vaso-occlusive crisis; OR
  • Recurrent tricorporal priapism defined as at least two episodes of an erection lasting >=4 hours involving the corpora cavernosa and corpus spongiosa; OR
  • Sickle hepatopathy defined as EITHER ferritin >1000mcg/L OR direct bilirubin >0.4 mg/dL at baseline; OR
  • Any one of the below complications:
  • Complication || Eligible for HSCT
  • Vaso-occlusive crises || More than 1 hospital admission per year while on a therapeutic dose of sickle cell treatment /medication
  • Acute chest syndrome (ACS) || Any ACS while on sickle cell treatment /medication
  • Osteonecrosis of 2 or more joints || And on sickle cell treatment /medication where total hemoglobin increase less than 1 g/dL or fetal hemoglobin increases <2.5 times the baseline level
  • Red cell alloimmunization || Total hemoglobin increase <1 g/dL while on therapeutic doses of sickle cell treatment /medication
  • Patients with beta-thalassemia who have grade 2 or 3 iron overload, determined by the presence of 2 or more of the following:
  • portal fibrosis by liver biopsy
  • inadequate chelation history (defined as failure to maintain adequate compliance with chelation with deferoxamine initiated within 18 months of the first transfusion and administered subcutaneously for 8-10 hours at least 5 days each week)
  • hepatomegaly of greater than 2 cm below the costochondral margin or by other imaging scans
  • 2. Non disease specific
  • Ages >=4 years (>=18 years for phase 1 portion of the study)
  • 6/6 HLA matched family donor available
  • Ability to comprehend and willing to sign an informed consent, assent obtained from minors
  • Negative serum or urine beta-HCG, when applicable
  • Agree to use birth control throughout the study and 12 months after drug product infusion.
  • Female subjects must agree to use a medically acceptable method of birth control such as oral contraceptive, intrauterine device, barrier and spermicide, or implant/injection from start of screening through 12 months after drug product infusion.
  • Male subjects must agree to use effective contraception (including condoms) from start of screening through 12 months after drug product infusion.
  • 3. Patients and Capacity to Consent
  • Subject provides informed consent prior to initiation of any study procedures.
  • Subject understands and agrees to comply with planned study procedures.
  • 4. Donor
  • Fully matched human leukocyte antigen (HLA) donors at A, B, C, and DR loci (8 of 8 or 10 of 10) are intended for this study. Donors age 4 or older and >=20 kg, eligible to donate hematopoietic stem cells, who are additionally willing to donate blood for research are eligible for this study. Donors will be evaluated in accordance with existing Standard NIH Policies and Procedures for determination of eligibility and suitability for clinical donation. Note that participation in this study is offered to all eligible donors, but is not required for a donor to make a stem cell donation, so it is possible that not all donors will enroll onto this study.

Who cannot join

  • Recipient exclusion criteria:
  • ECOG performance status of 3 or more, or Lanksy performance status of <40 (See Appendix A).
  • Diffusion capacity of carbon monoxide (DLCO) <35% predicted (corrected for hemoglobin and alveolar volume). This criterion may be omitted in young children (e.g. near age 5) or other individuals who may have difficulty understanding or complying with instructions of testing.
  • Baseline oxygen saturation of <85% or PaO2 <70
  • Left ventricular ejection fraction: <35% estimated by ECHO
  • Transaminases >5x upper limit of normal for age
Show all 12Show fewer
  • Evidence of uncontrolled bacterial, viral, or fungal infections (currently taking medication and progression of clinical symptoms) within one month prior to starting the conditioning regimen
  • Major anticipated illness or organ failure incompatible with survival from PBSC transplant.
  • Pregnant or breastfeeding
  • Donor exclusion criteria:
  • Pregnant or breastfeeding
  • Cognitively impaired subjects

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: Addition of JSP191 (C-kit Antibody) to Non-myeloablative Hematopoietic Cell Transplantation For Sickle Cell Disease and Beta-Thalassemia

Background:

Sickle cell disease (SCD) is an inherited disorder of the blood. It can damage a person s organs and cause serious illness and death. A blood stem cell transplant is the only potential cure for SCD. Treatments that improve survival rates are needed.

Read more

Objective:

To find out if a new antibody drug (briquilimab, JSP191) improves the success of a blood stem cell transplant

Eligibility:

People aged 13 or older who are eligible for a blood stem cell transplant to treat SCD. Healthy family members over age 13 who are matched to transplant recipients are also needed to donate blood.

Design:

Participants receiving transplants will undergo screening. They will have blood drawn. They will have tests of their breathing and heart function. They may have chest x-rays. A sample of marrow will be collected from a pelvic bone.

Participants will remain in the hospital about 30 days for the transplant and recovery. They will have a large intravenous line inserted into the upper arm or chest. The line will remain in place for the entire transplant and recovery period. The line will be used to draw blood as needed. It will also be used to administer the transplant stem cells as well as various drugs and blood transfusions. Participants will also receive some drugs by mouth.

Participants must remain within 1 hour of the NIH for 3 months after transplant. During that time, they will visit the clinic up to 2 times a week.

Follow-up visits will include tests to evaluate participants mental functions. They will have MRI scans of their brain and heart.

Read the detailed description

Study Description:

We propose to add briquilimab, an antibody targeting CD117 (c-Kit), to the 03-H-0170 regimen to improve myeloid chimerism, in patients considered at high risk for complications from or ineligible from standard myeloablative HSCT. Given the preclinical and clinical data, the addition of briquilimab has the potential to further deplete host lymphoid and myeloid cells to achieve a higher percentage of donor leukocyte engraftment without increased toxicity. Our prior non-myeloablative conditioning (NMA) regimen includes 1 mg/kg of alemtuzumab divided over 5 days, 300 cGy total body irradiation (TBI), and sirolimus for immune suppression. This regimen demonstrated a disease-free survival (DFS) and overall survival (OS) of 87% and 94% respectively, a 13% graft failure rate, no treatment related mortality (TRM), and no acute or chronic GVHD. A large proportion of patients achieves robust (>=98%) donor myeloid chimerism early, but this proportion decreases to 57% at 1, 54% at 2, and 49% at 3, and 50% at 4 years post-transplant. Monoclonal antibodies (mAb) targeting human stem cells (HSCs) is one strategy to improve DFS and may have synergy when combined with TBI as part of transplant conditioning regimen.

Objectives:

Primary Objective:

-To determine if addition of CD117 antibody (briquilimab) would increase proportion of patients with donor myeloid chimerism >=98% at 1 year post transplant

Secondary Objectives:

  • To measure briquilimab and alemtuzumab clearance at 1 and 2 years post transplant:
  • To compare CD14/15 and CD3 chimerism to protocol 03-H-0170
  • Estimate the proportion of patients with donor myeloid chimerism at or above 75%
  • To assess the usual transplant related parameters, such as count recovery, transfusion support, rates of GVHD, viral/bacterial infections, and rates of transplant related and overall mortality, and compare to those results in 03-H-0170

Endpoints:

Primary Endpoint:

-percent myeloid (CD14/15) chimerism

Secondary Endpoints:

  • Briquilimab antibody PK levels
  • Alemtuzumab levels
  • Percent T cell (CD3) chimerism
  • Day of neutrophil engraftment
  • Day of platelet engraftment
  • Rates of viral infection and/or reactivation
  • Rates of bacterial infection
  • Rates of acute and chronic GVHD
  • Transplant related mortality
  • Non-transplant related mortality
  • Rates of graft failure
  • Quality of life and neuropsychologic function
Being tested
TBI, Hydroxyurea, briquilimab, Filgrastim (G-CSF), Sirolimus
Keywords
Myeloid Chimerism, Lymphoid Cells, Myeloid Cells, Donor Leukocyte Engraftment, Non-Myeloablative Conditioning
Medical subject headings
Anemia, Sickle Cell, beta-Thalassemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TBIRadiation

    300 cGy total body irradiation (TBI, day -2)

  • HydroxyureaDrug

    Optimized 4-12 weeks prior to planned transplant date

  • briquilimabBiological

    briquilimab, anti-CD117 monoclonal antibody at 0.6mg/kg at day -11 prior to infusion of allogeneic HSCs

  • Filgrastim (G-CSF)Drug

    May be used to minimize the days of neutropenia, and may be administered beginning near day 10 post stem cell infusion at 5 mcg/kg (rounding to the nearest vial) at the discretion of investigator.

  • SirolimusDrug

    For immune suppression (day -1)

  • AlemtuzumabBiological

    Alemtuzumab 1 mg/kg of alemtuzumab divided over 5 days (-7 through -3),

  • PlerixaforDrug

    For autologous HSC collection; dose of plerixafor at 240 mcg/kg (capped at 20mg)

Study groups in NCT05357482
Study groupRoleWhat they receive
briquilimab in stem cell transplant recipients for SCDExperimentalAffected SCD and beta-thal subjects will receive briquilimab
Receives: Radiation: TBI; Drug: Hydroxyurea; Biological: briquilimab; Drug: Filgrastim (G-CSF); Drug: Sirolimus; Biological: Alemtuzumab; Drug: Plerixafor
Stem cell Donors of Recipients undergoing stem cell transplantNo interventionParticipants donate stem cells for recipient to undergo stem cell transplant

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. percent myeloid (CD14/15) chimerism

    The primary objective is to determine if addition of CD117 antibody (JSP191) would increase proportion of patients with donor myeloid chimerism =98% at 1 year post transplant.

    Measured: 1 year post transplant

Secondary outcomes (11)

  1. Transplant related mortality

    Transplant related mortality

    Measured: 1 and 2 years post transplant

  2. Rates of graft failure

    Rates of graft failure

    Measured: 1 and 2 years post transplant

  3. Rate of viral infection and/or reactivation

    Rate of viral infection and/or reactivation

    Measured: day 100

  4. Alemtuzumab levels

    To measure alemtuzumab clearance at 1 and 2 years post transplant

    Measured: day 100

  5. Rate of chronic GVHD

    Rate of chronic graft vs host disease (GvHD)

    Measured: 1 and 2 years post transplant

  6. Days to neutrophil engraftment

    Day of neutrophil engraftment

    Measured: day 100

  7. JSP antibody PK levels

    To measure JSP191 and alemtuzumab clearance at 1 and 2 years post transplant

    Measured: day 100

  8. Proportion of patients with donor myeloid chimerism at or above 75%

    Estimate the proportion of patients with donor myeloid chimerism at or above 75%

    Measured: 1 and 2 years post transplant

  9. Non-transplant related mortality

    Non-transplant related mortality

    Measured: 1 and 2 years post transplant

  10. Rate of bacterial infection

    Rate of bacterial infection

    Measured: 1 and 2 years post transplant

  11. Rates of acute GVHD

    Rate of acute graft vs host disease (GvHD)

    Measured: 1 and 2 years post transplant

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 May 2022
  2. Study start12 May 2022
  3. Primary completion31 Jan 2026
  4. Study completion31 Jan 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05357482
Sponsor's protocol ID
10000539
Other IDs
000539-H
Status last verified
10 Mar 2026
First submitted
30 Apr 2022
Last updated
12 Mar 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing TBI, Hydroxyurea and briquilimab in people with Sickle Cell Anemia and Beta Thalassemia, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 35 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 12 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

percent myeloid (CD14/15) chimerism (time frame: 1 year post transplant). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05357482.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Mar 2026.

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