Genome-Edited Cells for Sickle Cell Disease

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called OTQ923, a type of gene-edited stem cell therapy. The goal is to determine if it can safely increase fetal hemoglobin (a type of blood protein) to help reduce complications in people with sickle cell disease, a condition that causes painful episodes and other health issues due to misshaped red blood cells. Suitable candidates for this trial are those aged 2 to 40 with sickle cell disease, who experience severe symptoms like pain crises or acute chest syndrome, and have not had success with or cannot use hydroxyurea, a common medication for this condition. As a Phase 1 trial, this research focuses on understanding how OTQ923 works in people, offering participants the opportunity to be among the first to receive this innovative treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that OTQ923, a new treatment for sickle cell disease, has promising safety results. In early studies with a few participants, the treatment was generally well-tolerated. This treatment uses CRISPR-Cas9 technology to increase fetal hemoglobin, which can help reduce complications of sickle cell disease.

Some participants experienced mild side effects, but no serious problems occurred. The treatment changes specific genes in blood cells to improve their function. Although this is an early-phase study, the results suggest that OTQ923 could be a safe option for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for sickle cell disease, such as hydroxyurea or blood transfusions, OTQ923 uses genome-editing technology, which offers a groundbreaking approach. This treatment involves a single intravenous infusion that aims to directly modify the patient's cells to address the underlying genetic cause of sickle cell disease. Researchers are excited about OTQ923 because it has the potential to provide a long-term solution by correcting the genetic defect, potentially reducing or even eliminating the need for ongoing treatment. This could mean fewer hospital visits and a better quality of life for patients.

What evidence suggests that this trial's treatments could be effective for sickle cell disease?

Research has shown that OTQ923, a gene-editing treatment under study in this trial, holds promise for people with sickle cell disease. In one study, three participants experienced higher total hemoglobin levels after receiving OTQ923, indicating potential improvement in their condition. The treatment also reduced symptoms of sickle cell disease in these patients. Additionally, OTQ923 appears to lower the risk of strokes by promoting normal blood flow in the brain. These results suggest that OTQ923 could effectively manage sickle cell disease. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

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 am between 2 and 40 years old.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2215643

CRISPR-Cas9 Editing of the HBG1 and HBG2 Promoters to ... Three participants with severe sickle cell disease who received a single infusion of OTQ923 had sustained increases in total hemoglobin, fetal ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37646679/

CRISPR-Cas9 Editing of the HBG1 and HBG2 Promoters to ... Manifestations of sickle cell disease decreased during the follow-up period. Conclusions: CRISPR-Cas9 disruption of the HBG1 and HBG2 gene ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04443907

NCT04443907 | Study of Safety and Efficacy of Genome- ... This study evaluated a genome-edited, autologous, hematopoietic stem and progenitor cell (HSPC) product - OTQ923 to reduce the biologic activity of BCL11A.

4. sciencedirect.com sciencedirect.com/science/article/pii/S0268960X24000183

Gene Editing's breakthrough against sickle cell disease For SCD, recent Bluebird Bio trials have shown encouraging results, including corrected haematological parameters and reduced vaso-occlusive crises 15 months ...

5. sicklecellanemianews.com sicklecellanemianews.com/news/gene-editing-therapy-otq923-cuts-stroke-risk-3-scd-patients/

Gene-editing therapy OTQ923 cuts stroke risk in 3 SCD ... The gene-editing therapy OTQ923 normalized brain blood flow in 3 sickle cell disease patients, suggesting it may lower stroke risk, ...

6. cgtlive.com cgtlive.com/view/crispr-cas9-edited-therapy-otq923-early-promise-sickle-cell-disease

CRISPR-Cas9 Edited Therapy OTQ923 Displays Early ... The CRISPR–Cas9–edited CD34+ hematopoietic stem- and progenitor-cell therapy showed expected safety while inducing red cell fetal hemoglobin.