Gene Transfer for CGD

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

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: 12

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new gene therapy treatment for individuals with X-linked Chronic Granulomatous Disease (X-CGD), a condition that weakens the immune system and leads to serious infections. The treatment, G1X-CGD (Lentiviral Vector Transduced CD34+ Cells), involves taking a patient's own stem cells, adding a healthy version of the gene, and returning these cells to the patient to improve infection resistance. The trial seeks participants with X-CGD who have experienced severe infections or inflammation requiring hospital stays. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you must be able to take oral medication and adhere to a prophylactic regimen (preventive treatment). It's best to discuss your current medications with the trial team to get a clear answer.

Is there any evidence suggesting that this gene transfer treatment is likely to be safe for humans?

In a previous study, researchers found no evidence of serious side effects, such as cancer or unusual cell growth, when using the lentiviral vector in human stem cells. This finding suggests that the gene transfer treatment might be safe for people with X-Linked Chronic Granulomatous Disease (X-CGD). The treatment involves taking a person’s own stem cells, adding the healthy gene, and then reintroducing them into the body. So far, studies have not shown any major safety issues with this method, providing reassurance that the treatment is well-tolerated. However, it remains under testing, and researchers are closely monitoring for any potential problems. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Chronic Granulomatous Disease (CGD), such as antibiotics, antifungals, and interferon gamma, G1X-CGD introduces a novel approach by using a lentiviral vector to transduce CD34+ cells. This gene therapy directly addresses the genetic cause of X-linked CGD by adding a functional copy of the defective gene, potentially offering a long-term solution rather than just managing symptoms. Researchers are excited about G1X-CGD because it promises to correct the underlying issue at the cellular level, which could lead to more effective and lasting improvements for patients with this condition.

What evidence suggests that this gene transfer treatment might be an effective treatment for X-CGD?

Research has shown that lentiviral gene therapy could be a promising treatment for X-linked Chronic Granulomatous Disease (X-CGD). In studies, patients who received this therapy with their own altered stem cells experienced fewer infections related to the disease. This trial will evaluate the effectiveness of G1X-CGD, a lentiviral vector transduced CD34+ cell therapy, in improving immune function by correcting the faulty gene. Early trial results demonstrated improved survival rates in animal studies. Additionally, these studies reported no serious side effects. Overall, the evidence suggests that gene therapy might effectively manage X-CGD. ^{1 3 6 7 8}

Who Is on the Research Team?

Elizabeth M Kang, M.D.

Principal Investigator

National Institute of Allergy and Infectious Diseases (NIAID)

Are You a Good Fit for This Trial?

This trial is for people aged 3-60 with X-CGD, a condition where the immune system doesn't work right. They'll be screened with various tests including medical history, physical exam, heart and imaging tests, blood and lung function tests, plus bone marrow aspiration.

Inclusion Criteria

Must weigh at least 15 kg

My stem cell collection will follow NIH standard practices.

Parent/guardian willing to sign and date informed consent form for child, and where appropriate, child may sign assent

Exclusion Criteria

Tested positive (definitive) for the presence of multiple types (2 or more) of anti-platelet antibodies

My organ function is normal as required.

I have a perfect match donor for a transplant without high risk.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Multiple visits for various tests

Apheresis and Preparation

Participants undergo apheresis to collect stem cells and receive drugs to prepare for gene transfer

1-2 weeks

Inpatient stay for procedures

Gene Transfer and Chemotherapy

Participants receive chemotherapy and the gene transfer through a central line

4-5 weeks

Inpatient stay at NIH Clinical Center

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

12 outpatient visits over 2 years, plus local doctor visits

Long-term Follow-up

Participants enroll in another study for long-term follow-up visits

13 years

What Are the Treatments Tested in This Trial?

Interventions

• G1X-CGD (Lentiviral Vector Transduced CD34+ Cells)

Trial Overview Researchers are testing a gene transfer treatment using lentiviral vector transduced CD34+ cells to correct the immune deficiency in X-CGD patients. Participants will receive drugs like Sirolimus and Busulfan to prepare for receiving their own genetically corrected stem cells.

How Is the Trial Designed?

Group I: X-linked CGD Experimental Treatment 5 Interventions

Non-randomized single arm

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07113743

Part B- G1X-CGD (Lentiviral Vector Transduced CD34+ ... Researchers want to see if a lentiviral gene transfer treatment will have the ability to make the patient s immune system more normal, in particular reduce the ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7115833/

Lentiviral gene therapy for X-linked chronic granulomatous ... We report initial results of nine severely affected X-linked CGD (X-CGD) patients who received ex vivo autologous CD34+ hematopoietic stem and progenitor cell- ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0006497122079721

Lentiviral gene therapy for X-linked chronic granulomatous ... ... CGD HSPCs provided a complete survival benefit compared with X-CGD mice receiving CCLchim-transduced X-CGD HSPCs at an equal vector dose.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02234934

NCT02234934 | Study of Gene Therapy Using a Lentiviral ... Approximately 3-6 patients will be treated per site with a goal of 16 total patients to be treated with G1XCGD lentiviral vector. Detailed Description. The ...

5. cordis.europa.eu cordis.europa.eu/project/id/305011/reporting

Gene Therapy for X-linked Chronic Granulomatous Disease ... Extensive in vitro and in vivo genotoxicity studies found no evidence for adverse events related to the G1XCDG transduced cells. These results were eventually ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8575060/

Preclinical Optimization and Safety Studies of a New ... We report no evidence of adverse events, including mutagenesis and tumorigenesis, in human hematopoietic stem cells transduced with the lentiviral vector.

7. liebertpub.com liebertpub.com/doi/pdf/10.1089/humc.2017.245?download=true

Non-Clinical Efficacy and Safety Studies on G1XCGD, a ... ... CD34+ cells from a healthy donor; transduced: mice were transplanted with G1XCGD transduced XCGD-CD34+ cells. Numbers at the left of the ...

8. childrenshospital.org childrenshospital.org/clinical-trials/nct02234934

Study of Gene Therapy Using a Lentiviral Vector to Treat X ... This trial will evaluate a new lentiviral vector that may be able to correct the defect, but have much lower risk for the complication.