CSL200 Gene Therapy for Sickle Cell Disease

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: CSL Behring

Disqualifiers: HPRT deficiency, TPMT deficiency, Alpha thalassemia, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 48 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new gene therapy called CSL200 for adults with severe sickle cell disease. The goal is to determine the treatment's safety and its impact on disease symptoms. The study involves collecting specific blood cells, preparing the body with a mild chemotherapy drug, and then introducing the gene therapy. Suitable candidates have sickle cell disease with frequent severe pain episodes, past acute chest syndrome, or other serious symptoms affecting daily life. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop all current medications, but if you are on hydroxyurea, you will need to stop it before certain procedures in the trial.

Is there any evidence suggesting that CSL200 is likely to be safe for humans?

Research has shown that CSL200 is being tested for safety in individuals with severe sickle cell disease. This study is in an early phase, marking the first time CSL200 is being tried in humans for this condition. The primary focus is on how well participants tolerate the treatment and identifying any side effects.

CSL200 involves extracting certain cells from the blood, treating them, and reintroducing them into the body. This process aims to help the body produce healthier blood cells. While specific information on CSL200's tolerability is not yet available, the main goal of this phase is to monitor for side effects and ensure safety.

In similar early-phase studies, treatments are often tested on a small group to identify potential side effects and their severity. This helps researchers understand safety before proceeding to larger studies. Participants in this study will have their health and well-being closely monitored by the study team. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for severe sickle cell disease, which often include blood transfusions and hydroxyurea, CSL200 offers a groundbreaking approach by using gene therapy. Researchers are excited about CSL200 because it introduces a new mechanism: it involves an autologous enriched CD34+ cell fraction that has been modified with a lentiviral vector to produce human γ-globinG16D and short-hairpin RNA734. This innovative method aims to correct the underlying genetic cause of sickle cell disease, potentially providing a long-term solution rather than just managing symptoms. By targeting the disease at its genetic roots, CSL200 holds the promise of significantly improving the quality of life for patients with this condition.

What evidence suggests that CSL200 might be an effective treatment for severe sickle cell disease?

Research shows that CSL200, the treatment being studied in this trial, aims to help people with severe sickle cell disease through a special kind of gene therapy. This process involves taking a person's own blood cells, modifying them to add a new gene, and then reintroducing them into the body. The new gene is intended to produce a different type of hemoglobin, the protein in red blood cells that carries oxygen. This could reduce the number of sickle-shaped cells that cause problems in sickle cell disease. Early results suggest that this method might improve symptoms by increasing the number of healthier blood cells, but more research is needed to confirm its effectiveness. ^{1 2 4 6 7}

Who Is on the Research Team?

Study Director

Principal Investigator

CSL Behring

Are You a Good Fit for This Trial?

Inclusion Criteria

Diagnosis of sickle cell disease with the homozygous HbS homozygous genotype (HbSS) or an HbSβ thalassemia variant (ie, HbSβ0 thalassemia or HbSβ+ thalassemia) genotype, confirmed by hemoglobin studies.

Fetal hemoglobin (HbF) ≤ 15%.

≥ 2 episodes of acute chest syndrome in the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Mobilization and Apheresis

Collection of CD34+ hematopoietic stem/progenitor cells by apheresis after mobilization with plerixafor

Up to 2 days

Conditioning

Reduced intensity conditioning with melphalan

2 days

Treatment

Administration of CSL200 and monitoring for adverse events

Up to 48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• CSL200

How Is the Trial Designed?

Group I: CSL200 Experimental Treatment 1 Intervention

Autologous enriched CD34+ cell fraction that contains CD34+ cells transduced with lentiviral vector encoding human γ-globinG16D and short-hairpin RNA734

Who Is Running the Clinical Trial?

CSL Behring

Lead Sponsor

Trials

204

Recruited

1,207,000+

Dr. Paul McKenzie

CSL Behring

Chief Executive Officer since 2023

PhD in Chemical Engineering from Carnegie Mellon University, B.S. in Chemical Engineering from the University of Pennsylvania

Dr. Bill Mezzanotte

CSL Behring

Chief Medical Officer since 2021

MD from Duke University

Citations

1. clinicaltrials.gov clinicaltrials.gov/show/NCT04091737

CSL200 Gene Therapy in Adults With Severe Sickle Cell ... This is a phase 1 pilot study of CSL200 in adult subjects with severe sickle cell disease. The primary objectives of this study are to evaluate the safety ...

2. withpower.com withpower.com/trial/phase-1-anemia-sickle-cell-9-2019-2e765

CSL200 Gene Therapy in Adults With Severe Sickle Cell ... This trial is testing CSL200, a treatment for adults with severe sickle cell disease. It involves collecting special blood cells from the patient.

3. cdek.pharmacy.purdue.edu cdek.pharmacy.purdue.edu/trial/NCT04091737/

Trial | NCT04091737 This is a phase 1 pilot study of CSL200 in adult subjects with severe sickle cell disease. The primary objectives of this study are to evaluate the safety ...

4. scge.mcw.edu scge.mcw.edu/platform/data/clinicalTrials/report/NCT04091737

CSL200 Gene Therapy in Adults With Severe Sickle Cell ... This is a phase 1 pilot study of CSL200 in adult subjects with severe sickle cell disease. The primary objectives of this study are to evaluate the safety ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8171369/

Innovative Treatments for Rare Anemias - PMC CSL Behring, 04091737, Autologous enriched CD34+ cell fraction that contains CD34+ cells transduced with LV encoding human γ-globinG16D and ...

6. ctv.veeva.com ctv.veeva.com/study/csl200-gene-therapy-in-adults-with-severe-sickle-cell-disease

CSL200 Gene Therapy in Adults With Severe Sickle Cell ... The primary objectives of this study are to evaluate the safety of the following: collection of CD34+ hematopoietic stem / progenitor cells by ...

7. bioworld.com bioworld.com/articles/674071-phase-i-study-of-csl-200-gene-therapy-in-adults-with-severe-sickle-cell-disease

Phase I study of CSL-200 gene therapy in adults ... The study's primary objectives are to evaluate the safety of the collection of CD34+ hematopoietic stem and progenitor cells by apheresis after ...