What is the mechanism of action of this treatment?

Chronic Granulomatous Disease (CGD) is treated primarily through gene therapy, bone marrow transplantation, and antimicrobial prophylaxis. The G1XCGD Lentiviral Vector Gene Therapy involves transducing autologous bone marrow CD34+ cells with a lentiviral vector containing the human CGD gene, which corrects the genetic defect in CGD patients. This therapy enables the production of functional white blood cells capable of effectively killing bacteria and fungi, thereby reducing infections and inflammation. This approach is significant for CGD patients as it offers a potential long-term solution by addressing the root cause of the disease, improving immune function, and reducing the risk of severe infections and organ damage.

What side effects are associated with this type of intervention?

Common treatments for Chronic Granulomatous Disease (CGD), such as gene therapy and bone marrow transplantation, have several known side effects. Chemotherapy used for bone marrow conditioning can cause myelosuppression, increasing the risk of infections and potential organ toxicity. Gene therapy using viral vectors carries the risk of insertional mutagenesis, which may lead to myelodysplasia or leukemia-like growth of blood cells. Additionally, there are risks of immune reactions and graft-versus-host disease (GVHD) associated with bone marrow transplantation.

What prior FDA approvals exist?

The FDA has approved several treatments for Chronic Granulomatous Disease (CGD), focusing primarily on gene therapy approaches. One notable treatment is the Strimvelis gene therapy, which was approved in Europe for ADA-SCID but represents a similar approach to correcting genetic defects in immune disorders. For CGD specifically, investigational treatments like the G1XCGD Lentiviral Vector Gene Therapy are being studied, which involve transducing autologous bone marrow CD34+ cells with a lentiviral vector containing the human CGD gene to correct the genetic defect. These therapies aim to restore the function of white blood cells in effectively killing bacteria and fungi, thereby reducing the morbidity associated with CGD.

What other types of research exist?

Promising alternatives to G1XCGD Lentiviral Vector Gene Therapy for CGD patients include: 1) CRISPR-Cas9 gene editing, which allows precise correction of genetic defects; 2) Hematopoietic stem cell transplantation (HSCT) with improved conditioning regimens to enhance engraftment and reduce complications; 3) Use of safer viral vectors, such as adeno-associated virus (AAV) vectors, which have a lower risk of insertional mutagenesis; and 4) Allogeneic stem cell transplantation from matched or haploidentical donors, which may offer a curative option with advancements in graft-versus-host disease (GVHD) management.

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Gene Therapy

Gene Therapy for Chronic Granulomatous Disease

Phase 1 & 2

Recruiting

Led By Caroline Y. Kuo, MD

Research Sponsored by University of California, Los Angeles

Eligibility Criteria Checklist

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

Must have

Male X-CGD patients > 23 months of age with molecular diagnosis confirmed by DNA sequencing and supported by laboratory evidence for absent or reduction > 95% of the biochemical activity of the NADPH-oxidase

Must not have co-infection with Human Immunodeficiency Virus (HIV)-1 or -2, hepatitis B virus or hepatitis C virus, adenovirus, parvovirus B 19, toxoplasmosis, or active infection with CMV

Must not have

Contraindication for leukapheresis or bone marrow harvest (anemia Hb <8g/dl, cardiovascular instability, severe coagulopathy)

Ineligible for autologous HSCT by the criteria at the clinical site

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial involves taking a patient's own stem cells, correcting a genetic defect in a lab, and then reintroducing these modified cells back into the patient. It targets individuals with Chronic Granulomatous Disease (CGD), a condition where white blood cells can't effectively fight infections. The treatment uses a method to insert a healthy gene into the patient's stem cells, enabling them to produce functional white blood cells. Gene therapy has shown promise in treating Chronic Granulomatous Disease (CGD) by using corrected stem cells.

Who is the study for?

This trial is for male patients over 23 months old with X-linked Chronic Granulomatous Disease (CGD), confirmed by DNA tests and lab evidence. They must have had severe infections despite treatment, no perfect bone marrow donor match, and be free of certain viruses like HIV or hepatitis. Patients need to consent to the study's procedures.

What is being tested?

The trial is testing a new gene therapy using a lentiviral vector called G1XCGD in CGD patients. It involves taking the patient's own bone marrow cells, modifying them with this vector to correct the genetic defect, then returning them back into the patient after chemotherapy conditioning.

What are the potential side effects?

Potential side effects may include reactions related to bone marrow harvest and infusion such as pain or bleeding, complications from chemotherapy like nausea or hair loss, and risks associated with gene therapy which could range from mild immune responses to more serious conditions affecting blood cell growth.

Eligibility Criteria

Inclusion Criteria

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

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I am a male over 23 months old with confirmed X-CGD and very low NADPH-oxidase activity.

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I do not have HIV, hepatitis B or C, adenovirus, parvovirus B19, toxoplasmosis, or an active CMV infection.

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I don't have a perfect match donor in the national registries.

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I have had a severe infection or inflammation that needed hospital care despite treatment.

Exclusion Criteria

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

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I cannot undergo leukapheresis or bone marrow harvest due to anemia, heart issues, or severe bleeding disorders.

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I am not eligible for a stem cell transplant using my own cells.

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I am over 12 years old or weigh more than 40kg if 12 or younger.

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I am younger than 23 months old.

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I have a perfect match donor for my transplant.

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My organ functions are within normal ranges as required.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Granulocyte

The incidence of adverse events assessed by CTCAE v4

Other study objectives

Immunophenotyping

Concentration of gp91 protein produced in response to the corrected gene

Awards & Highlights

No Placebo-Only Group

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

Trial Design

2Treatment groups

Experimental Treatment

Group I: Lentiviral G1XCGD Gene Therapy, Part BExperimental Treatment1 Intervention

Transplantation with autologous CD34+ stem cells corrected with X1XCGD lentiviral vector after modified myeloreductive conditioning including increased monitoring and rescue treatment

Group II: Lentiviral G1XCGD Gene Therapy, Part AExperimental Treatment1 Intervention

Transplantation with autologous CD34+ stem cells corrected with X1XCGD lentiviral vector after myeloreductive conditioning

0 / 10Eligibility 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

Chronic Granulomatous Disease (CGD) is treated primarily through gene therapy, bone marrow transplantation, and antimicrobial prophylaxis. The G1XCGD Lentiviral Vector Gene Therapy involves transducing autologous bone marrow CD34+ cells with a lentiviral vector containing the human CGD gene, which corrects the genetic defect in CGD patients. This therapy enables the production of functional white blood cells capable of effectively killing bacteria and fungi, thereby reducing infections and inflammation. This approach is significant for CGD patients as it offers a potential long-term solution by addressing the root cause of the disease, improving immune function, and reducing the risk of severe infections and organ damage.