What side effects are associated with this type of intervention?

Hydroxyurea, a common treatment for Sickle Cell Disease, is known to cause side effects such as bone marrow suppression, leading to decreased white blood cell and platelet counts, which can increase infection risk and bleeding. Other side effects include gastrointestinal disturbances, skin and nail changes, and potential infertility in men. Chronic transfusions, another treatment, can lead to iron overload, requiring chelation therapy. Hematopoietic stem cell transplantation, while potentially curative, carries risks of graft-versus-host disease, infection, and organ damage. Investigational therapies like genome editing to increase HbF are still under study, but potential risks include off-target genetic effects and long-term safety concerns.

What prior FDA approvals exist?

Hydroxyurea is one of the most established FDA-approved treatments for Sickle Cell Disease, known for its ability to increase fetal hemoglobin (HbF) levels and reduce vaso-occlusive events. While hydroxyurea does not specifically target BCL11A, it shares the goal of increasing HbF to ameliorate SCD symptoms. Other FDA-approved treatments include L-glutamine (Endari), which reduces oxidative stress, and voxelotor (Oxbryta), which inhibits hemoglobin polymerization. Crizanlizumab (Adakveo) is another approved drug that targets P-selectin to reduce pain crises. These treatments collectively aim to reduce the frequency and severity of SCD complications, though they do not specifically involve genome editing or direct modulation of BCL11A activity like OTQ923.

What other types of research exist?

Promising novel alternatives to OTQ923 for Sickle Cell Disease patients include lovo-cel (bb1111; LentiGlobin for SCD), which involves autologous transplantation of hematopoietic stem and progenitor cells transduced with a lentiviral vector encoding a modified β-globin gene. Additionally, hydroxyurea remains a well-established therapy with extensive evidence supporting its efficacy in reducing complications and improving quality of life in SCD patients.

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Gene Therapy

Genome-Edited Cells for Sickle Cell Disease

Q: What is the mechanism of action of this treatment?

Common treatments for Sickle Cell Disease (SCD) include hydroxyurea, l-glutamine, and investigational therapies like genome editing to reduce BCL11A activity. Hydroxyurea increases fetal hemoglobin (HbF) production, which reduces the sickling of red blood cells and decreases vaso-occlusive crises (VOC). L-glutamine helps reduce oxidative stress in red blood cells, thereby decreasing the frequency of pain crises. Investigational therapies, such as genome editing to reduce BCL11A activity, aim to increase HbF levels by modifying genetic expression, offering a potential curative approach. These treatments are crucial as they target the underlying pathophysiology of SCD, improving patient outcomes and quality of life.

Phase 1

Waitlist Available

Research Sponsored by Novartis Pharmaceuticals

Eligibility Criteria Checklist

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

Must have

Subjects who have failed, not tolerated or refused hydroxyurea therapy

Performance status >70% (Karnofsky for subjects >16 years of age and Lansky for subjects <16 years of age)

Must not have

Severe or progressive arteriopathy or cerebrovascular disease, including Moyamoya

Active known malignancy, myelodysplasia, abnormal cytogenetics or immunodeficiency

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 24 months

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

While specific side effects of OTQ923 aren't listed here, similar treatments may cause immune reactions, infection risk due to bone marrow suppression during stem cell transplant preparation, and potential long-term risks related to genome editing.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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I am mostly active and can care for myself.

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

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I am between 2 and 40 years old.

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I have been diagnosed with sickle cell disease.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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

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

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I have a family member who is a match for a stem cell transplant.

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I have had a stem cell transplant or gene therapy.

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I currently have a serious infection.

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I have liver cirrhosis, severe liver scarring, or active hepatitis.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 24 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 24 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 24 months for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Fetal hemoglobin (HbF) expression after hematopoietic stem cell transplant (HSCT)

Number of participants with adverse events and serious adverse events

Time to reach absolute neutrophil count (ANC) ≥500/μL for 3 consecutive days

Secondary study objectives

Durability of hematologic engraftment

Evaluation of effect on patient-reported outcomes from baseline and post-HSCT with age appropriate patient reported measures

Number of participants with change from baseline of annualized SCD complications (aggregate of VOC, ACS, priapism and stroke) and if relevant, rate of transfusion by 65%

+8 more

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: OTQ923Experimental Treatment1 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.

0 / 12Eligibility criteria met

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, l-glutamine, and investigational therapies like genome editing to reduce BCL11A activity. Hydroxyurea increases fetal hemoglobin (HbF) production, which reduces the sickling of red blood cells and decreases vaso-occlusive crises (VOC). L-glutamine helps reduce oxidative stress in red blood cells, thereby decreasing the frequency of pain crises. Investigational therapies, such as genome editing to reduce BCL11A activity, aim to increase HbF levels by modifying genetic expression, offering a potential curative approach. These treatments are crucial as they target the underlying pathophysiology of SCD, improving patient outcomes and quality of life.

A reanalysis of pain crises data from the pivotal l-glutamine in sickle cell disease trial.Haemoglobin F modulation in childhood sickle cell disease.