Genome-Edited Cells for Sickle Cell Disease

Recruiting at 8 trial locations

Overseen By Novartis Pharmaceuticals

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Novartis Pharmaceuticals

Disqualifiers: HIV, Malignancy, Hepatitis, Moyamoya, others

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

Compensation: Varies

Number of Visits: Unknown

4 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial uses genetically modified blood stem cells from patients to treat Sickle Cell Disease. It works by reducing a gene's activity to increase beneficial fetal hemoglobin, aiming to lessen disease complications. The treatment involves a gene therapy that helps produce a type of hemoglobin that reduces the effects of the disease.

Eligibility Criteria

This trial is for people aged 2-40 with sickle cell disease who've had severe symptoms like pain crises, acute chest syndrome, or stroke. It's open to those who can't tolerate or haven't benefited from hydroxyurea therapy and have a performance status over 70%. People with liver issues, iron overload, certain infections or cancers, previous transplants or gene therapy are not eligible.

Inclusion Criteria

I have stopped or refused hydroxyurea due to side effects or choice.

I am mostly active and can care for myself.

I have had severe symptoms like pain crises, chest issues, or needed regular blood transfusions.

Exclusion Criteria

I do not have severe or worsening artery or brain vessel disease.

I have an active cancer, blood disorder, genetic abnormalities, or a weak immune system.

I have not had brain surgery or procedures for Moyamoya disease in the last year.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Apheresis and Genome Editing

Apheresis of mobilized hematopoietic stem and progenitor cells (HSPCs), followed by ex vivo CRISPR/Cas9-mediated genome editing and expansion

4-6 weeks

Myeloablative Conditioning and HSCT

Participants undergo myeloablative conditioning followed by autologous hematopoietic stem cell transplant (HSCT)

6-8 weeks

Primary Follow-up

Participants are monitored for safety and efficacy, including fetal hemoglobin expression and adverse events

6 months

Extended Follow-up

Long-term follow-up to assess durability of hematologic engraftment and overall survival

up to 24 months

Treatment Details

Interventions

• HIX763
• OTQ923

Trial Overview The study tests OTQ923 - a genome-edited stem cell treatment aimed at increasing fetal hemoglobin to alleviate sickle cell complications. Participants receive their own modified cells back to potentially reduce the severity of their condition.

Participant Groups

Group I: OTQ923 Experimental Treatment 1 Intervention

Single intravenous infusion of OTQ923 Part A - Adults treated with OTQ923; Part B - Children age 2-17 treated with OTQ923 based on review of data from Part A by Health agency after a formal interim analysis.

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD