Gene Therapy for Chronic Granulomatous Disease

Recruiting at 2 trial locations

Overseen By Augustine Fernandes, PhD

Age: Any Age

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: University of California, Los Angeles

Must not be taking: Gamma-interferon

Disqualifiers: HIV, Hepatitis B, Hepatitis C, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have taken gamma-interferon within 30 days before the infusion of the gene-modified cells.

Is G1XCGD Gene Therapy safe for humans?

Studies in mice showed no toxicity from G1XCGD Gene Therapy, and human trials reported no serious adverse effects, although some gene integration near certain genes was observed without causing any health issues. ^{1 2 3 4 5}

How is the G1XCGD Gene Therapy treatment different from other treatments for chronic granulomatous disease?

G1XCGD Gene Therapy is unique because it involves modifying a patient's own stem cells to correct the genetic defect causing chronic granulomatous disease, potentially providing a long-term solution. Unlike traditional treatments that may require bone marrow transplants from donors, this therapy uses the patient's own cells, reducing the risk of rejection and making it accessible to more patients. ^{3 6 7 8 9}

What data supports the effectiveness of the G1XCGD Gene Therapy treatment for chronic granulomatous disease?

Research shows that gene therapy for chronic granulomatous disease (CGD) has led to stable improvements in patients, with six out of nine patients showing no new infections and being able to stop preventive antibiotics after 12 months. This suggests that gene therapy can be a promising approach for treating CGD. ^{6 8 10 11 12}

Who Is on the Research Team?

Donald B. Kohn, MD

Principal Investigator

University of California, Los Angeles

Caroline Y. Kuo, MD

Principal Investigator

University of California, Los Angeles

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

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

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

I have signed the consent form, or if under 18, I have given my assent.

Exclusion Criteria

I haven't received gamma-interferon within the last 30 days.

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

Contraindication for administration of conditioning medication (Known sensitivity to Busulfan)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning

Participants undergo myeloreductive conditioning to prepare for stem cell transplantation

2 weeks

Treatment

Transplantation with autologous CD34+ stem cells corrected with G1XCGD lentiviral vector

12 months

Regular monitoring visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• G1XCGD Gene Therapy

Trial Overview 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.

How Is the Trial Designed?

Group I: Lentiviral G1XCGD Gene Therapy, Part B Experimental Treatment 1 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 A Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials

1,594

Recruited

10,430,000+

Boston Children's Hospital

Collaborator

Trials

801

Recruited

5,584,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Genethon

Collaborator

Trials

16

Recruited

600+

California Institute for Regenerative Medicine (CIRM)

Collaborator

Trials

70

Recruited

3,300+

Published Research Related to This Trial

Ex vivo gene therapy for chronic granulomatous disease (CGD) has previously shown only temporary improvements in neutrophil function, with less than 0.1% of neutrophils corrected.

The next generation of clinical trials will use advanced RD114 envelope pseudotyped vectors and non-ablative marrow conditioning, which could significantly enhance the effectiveness of gene therapy for CGD by improving the transduction of stem cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progress toward effective gene therapy for chronic granulomatous disease. Malech, HL., Choi, U., Brenner, S.[2017]

Using an adenovirus vector to deliver the p47phox gene to monocytes from patients with chronic granulomatous disease (CGD) successfully restored NADPH oxidase activity, indicating a potential therapeutic strategy.

This method not only provides a rapid way to diagnose the specific molecular defect in CGD but also shows promise for future gene therapy applications to correct the cellular defect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene transfer to primary chronic granulomatous disease monocytes. Thrasher, AJ., Casimir, CM., Kinnon, C., et al.[2019]

In a first-in-human study involving nine patients with X-linked chronic granulomatous disease (X-CGD), autologous gene therapy showed promising safety and efficacy, with six out of seven surviving patients demonstrating stable gene expression and functional immune recovery at 12 months.

The treatment led to a significant reduction in CGD-related infections, with six patients able to stop antibiotic prophylaxis, indicating that this gene therapy could effectively enhance immunity in CGD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lentiviral gene therapy for X-linked chronic granulomatous disease. Kohn, DB., Booth, C., Kang, EM., et al.[2021]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Chronic granulomatous disease: Clinical, molecular, and therapeutic aspects. [2022]

2. Japan pubmed.ncbi.nlm.nih.gov

Progress toward effective gene therapy for chronic granulomatous disease. [2017]

3. England pubmed.ncbi.nlm.nih.gov

Gene transfer to primary chronic granulomatous disease monocytes. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Lentiviral gene therapy for X-linked chronic granulomatous disease. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Gene therapy of chronic granulomatous disease: the engraftment dilemma. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Toxicity of repeated intravenous injection of gene therapeutics for X-CGD in mice. [2012]

7. United States pubmed.ncbi.nlm.nih.gov

Retroviral gene therapy for X-linked chronic granulomatous disease: results from phase I/II trial. [2021]

8. Italy pubmed.ncbi.nlm.nih.gov

The expression of full length Gp91-phox protein is associated with reduced amphotropic retroviral production. [2017]

9. United States pubmed.ncbi.nlm.nih.gov

Gene therapy for chronic granulomatous disease. [2017]

10. United States pubmed.ncbi.nlm.nih.gov

Retrovirus gene therapy for X-linked chronic granulomatous disease can achieve stable long-term correction of oxidase activity in peripheral blood neutrophils. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

Progress in gene therapy for chronic granulomatous disease. [2017]

12. England pubmed.ncbi.nlm.nih.gov

Gene therapy for chronic granulomatous disease. [2012]