Siplizumab for Sickle Cell Anemia

(CD2 SCD Trial)

Overseen By Markus Y. Mapara

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Markus Mapara

Disqualifiers: Pulmonary dysfunction, Severe cardiac dysfunction, HIV, others

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

Compensation: Varies

Number of Visits: 5

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called siplizumab for individuals with sickle cell anemia undergoing a stem cell transplant. The primary goal is to determine if the drug can safely prevent serious complications such as Graft versus Host Disease (GVHD) and graft failure, which may occur after a transplant. Participants will receive five infusions of siplizumab around the time of their transplant. The trial seeks individuals with sickle cell anemia who have experienced serious health issues, including strokes, frequent pain crises, or lung and kidney problems. As a Phase 1, Phase 2 trial, it aims to understand how siplizumab works in people and measure its effectiveness in a smaller group, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

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

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

Research has shown that siplizumab is generally safe. In earlier studies, patients handled the treatment well, and the drug remained active in the body for three days after the second dose. Previous research has also examined siplizumab for conditions like type 1 diabetes and autoimmune diseases, supporting its safety. Although this trial focuses on sickle cell anemia, these findings suggest that siplizumab is usually well-tolerated in people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Siplizumab is unique because it targets the CD2 receptor on T-cells, which plays a role in the immune response associated with sickle cell anemia. Unlike the standard of care treatments such as hydroxyurea or blood transfusions, which primarily focus on managing symptoms or complications, siplizumab offers a novel approach by potentially modifying the underlying immune processes. Researchers are excited because this could mean a more targeted treatment that addresses the root causes of the disease, potentially improving outcomes for patients.

What evidence suggests that siplizumab might be an effective treatment for sickle cell anemia?

Research has shown that siplizumab, the investigational treatment in this trial, might help manage issues in patients with sickle cell anemia undergoing a stem cell transplant. This treatment may lower the risk of graft versus host disease (GVHD), a condition where new cells attack the patient's body, by targeting specific immune cells that cause this problem. Early results suggest that siplizumab might reduce the chances of transplant failure, increasing the likelihood of success. While researchers are still learning about siplizumab's effectiveness specifically for sickle cell anemia, its potential to control immune responses appears promising. ^{1 3 6 7 8}

Who Is on the Research Team?

Markus Mapara, MD

Principal Investigator

Columbia University

Are You a Good Fit for This Trial?

This trial is for people with Sickle Cell Disease (SCD) who've had a stroke, frequent pain crises or acute chest syndrome despite treatment, need regular blood transfusions, have heart issues like high blood flow velocity through the tricuspid valve or pulmonary hypertension, kidney disease including those on dialysis, recurrent priapism, and are not pregnant. They should be fairly active (ECOG status of 2 or better) and have a left ventricular ejection fraction of 40% or greater.

Inclusion Criteria

I have chronic kidney disease or am on dialysis.

Recipient cannot be pregnant or lactating.

My heart pumps well, with an ejection fraction of 40% or more.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning and Transplantation

Participants receive 5 infusions of siplizumab and undergo stem cell transplantation

3 weeks

5 visits (in-person)

Initial Follow-up

Participants are monitored for graft failure, GVHD, and other complications

100 days

Regular visits (in-person)

Extended Follow-up

Participants are monitored for long-term outcomes including immune reconstitution and GVHD

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Siplizumab

Trial Overview The study tests if siplizumab can safely prevent Graft versus Host Disease (GVHD) and graft failure in patients receiving stem cell transplants for SCD. Participants will get five infusions of siplizumab along with other treatments like cyclophosphamide and total body irradiation to support the transplant process.

How Is the Trial Designed?

Group I: Siplizumab Experimental Treatment 8 Interventions

Participants will receive 5 infusions of siplizumab. The first dose is given 14 days prior to the infusion of stem cells; the second dose is given 6 days before infusion; and doses 3, 4, and 5 are given on the day before, day of, and day after stem cell infusion.

Who Is Running the Clinical Trial?

Markus Mapara

Lead Sponsor

Trials

1

Recruited

20+

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

ITB-Med LLC

Industry Sponsor

Trials

12

Recruited

390+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06078696

Siplizumab for Sickle Cell Disease Transplant The purpose of this study is to find out whether siplizumab is safe and effective for patients with SCD undergoing an allogeneic transplant and to prevent ...

2. clinicaltrials.eu clinicaltrials.eu/inn/siplizumab/

Siplizumab – Application in Therapy and Current Clinical ... This article explores the ongoing research into siplizumab's potential as a treatment for diseases like type 1 diabetes, hidradenitis suppurativa, autoimmune ...

3. biospace.com biospace.com/gbt-presents-positive-results-from-phase-1-study-of-gbt021601-in-patients-with-sickle-cell-disease-and-healthy-volunteers-at-ash-annual-meeting-and-exposition

GBT Presents Positive Results from Phase 1 Study of ... “These Phase 1 data of GBT601 are very encouraging and demonstrate that in sickle cell disease patients we can achieve a high target hemoglobin ...

4. aging.networkofcare.org aging.networkofcare.org/sanmateo/CommunityResources/ClinicalTrials/Detail/NCT06078696?keyword=%22Hemoglobin%22

Siplizumab for Sickle Cell Disease Transplant It is designed to determine the safety and feasibility of hematopoietic stem cell transplantation for patients with advanced sickle cell disease using in vivo T ...

5. firstwordpharma.com firstwordpharma.com/story/5592499

GBT Presents Positive New Real-World Evidence Data at ... Positive results from Phase 1 study of GBT601, including incremental new data, support advancing into planned Phase 2/3 trial by mid-year.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/19917362/

Safety profile, pharmacokinetics, and pharmacodynamics ... Siplizumab exhibited an acceptable safety profile in this study. Detectable siplizumab concentrations were maintained for 3 days after the second dose.

7. researchgate.net researchgate.net/publication/356500936_GBT021601_a_Next_Generation_HbS_Polymerization_Inhibitor_Results_of_Safety_Tolerability_Pharmacokinetics_and_Pharmacodynamics_in_Adults_Living_with_Sickle_Cell_Disease_and_Healthy_Volunteers

GBT021601, a Next Generation HbS Polymerization Inhibitor Given its drug exposure, GBT021601 has the capacity to achieve a targeted Hb occupancy and attain the desired hematological effect at low doses, ...

8. recruit.cumc.columbia.edu recruit.cumc.columbia.edu/studyinfopage/2406

Study of Siplizumab-Based Treatment in Patients ... - RecruitMe The purpose of this research study is to see if the anti-rejection medications that patients normally take after transplant can be reduced or stopped completely ...