What side effects are associated with this type of intervention?

The most common treatments for Sickle Cell Disease (SCD) include hydroxyurea, chronic transfusions, and hematopoietic stem cell transplantation. Hydroxyurea can cause side effects such as cytopenias, mucocutaneous ulcers, diarrhea, peripheral neuropathy, skin cancer, and potential teratogenicity. Chronic transfusions carry risks of iron overload, alloimmunization, and transfusion reactions. Hematopoietic stem cell transplantation, while potentially curative, can lead to graft-versus-host disease, infections, and organ toxicity. Investigational therapies like Motixafortide (CXCR4 inhibition) and Natalizumab (VLA-4 inhibition) are being studied for their safety and efficacy, but specific side effects are not yet well-documented.

What prior FDA approvals exist?

The FDA has approved hydroxyurea for the treatment of Sickle Cell Disease (SCD) due to its efficacy in reducing vaso-occlusive pain and other complications. Additionally, investigational therapies such as hematopoietic stem cell transplantation and gene therapies are being explored for their curative potential. While Motixafortide (CXCR4 inhibition) and Natalizumab (VLA-4 inhibition) are currently under investigation for their ability to mobilize hematopoietic stem cells for gene therapies in SCD, they have not yet received FDA approval for this specific use.

What other types of research exist?

Promising novel alternatives for Sickle Cell Disease treatment in 2024 include hematopoietic stem cell (HSC)-based gene therapies, which offer curative potential with decreased toxicity compared to traditional transplantation methods. These therapies depend on effective HSC mobilization, which is being explored with agents like Motixafortide and Natalizumab. Additionally, new medications that modify the pathogenesis of SCD-associated vaso-occlusion are also being developed and may provide alternative treatment options.

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Motixafortide + Natalizumab for Sickle Cell Disease

Phase 1

Recruiting

Led By Zachary Crees, M.D.

Research Sponsored by Washington University School of Medicine

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from start of treatment through 8 weeks following completion of all treatment (estimated to be 16 weeks and 4 days)

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing two drugs, motixafortide and natalizumab, to help patients with sickle cell disease. These drugs aim to move more stem cells from the bone marrow into the blood, making it easier to collect them for gene therapy. Natalizumab is also used to treat multiple sclerosis.

Who is the study for?

Adults aged 18-40 with sickle cell disease (hemoglobin SS or Sβ0 genotype), able to pause certain medications, and have specific health criteria like a platelet count of at least 75,000/uL. They must not be pregnant, agree to use contraception during the study and for three months after, and cannot have had previous gene therapies or certain immunosuppressants.

What is being tested?

The trial is testing Motixafortide and Natalizumab's ability to mobilize hematopoietic stem cells in preparation for gene therapy in sickle cell disease patients. It aims to see if these drugs can safely increase the number of stem cells available for treatment without unacceptable risks.

What are the potential side effects?

Potential side effects may include reactions related to immune system suppression given that Natalizumab affects immune function. Specific side effects are not listed but could align with those typical of agents affecting blood cell mobilization such as bone pain, fatigue, headache, nausea.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from start of treatment through 8 weeks following completion of all treatment (estimated to be 16 weeks and 4 days)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from start of treatment through 8 weeks following completion of all treatment (estimated to be 16 weeks and 4 days)

This trial's timeline: 3 weeks for screening, Varies for treatment, and from start of treatment through 8 weeks following completion of all treatment (estimated to be 16 weeks and 4 days) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Safety and tolerability as assessed by the incidence of dose-limiting toxicities (DLTs)

Secondary study objectives

Frequency of adverse events

Leukapheresis

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Motixafortide followed by Motixafortide + NatalizumabExperimental Treatment3 Interventions

* Consenting and eligible patients will receive a single subcutaneous injection of motixafortide, followed by leukapheresis. Patient will then be followed for 8 weeks for adverse event monitoring. * Following the 8-week monitoring period, patients will receive a single IV infusion natalizumab, then approximately 32 hours later, a single subcutaneous injection of motixafortide, followed by leukapheresis. Patients will then be followed for 8 weeks for adverse event monitoring.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Leukapheresis

2016

Completed Phase 2

~710

Natalizumab

2003

Completed Phase 4

~5310

Do I qualify?Apply below to find out

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Sickle Cell Disease (SCD) include hydroxyurea, which increases fetal hemoglobin (HbF) to reduce red blood cell sickling and vaso-occlusive episodes, and chronic transfusions, which dilute sickle hemoglobin (HbS) with normal hemoglobin to prevent complications. Investigational therapies like Motixafortide (CXCR4 inhibition) and Natalizumab (VLA-4 inhibition) focus on mobilizing hematopoietic stem cells and reducing cell adhesion, respectively, to improve blood flow and reduce vaso-occlusion. These treatments are vital as they target the underlying mechanisms of SCD, aiming to alleviate pain, prevent complications, and enhance the quality of life for patients.

Regular long-term red blood cell transfusions for managing chronic chest complications in sickle cell disease.Sickle-cell disease.