pCCLCHIM-p47 (Lentiviral Vector Transduced CD34 Plus Cells) in Patients With p47 Autosomal Recessive Chronic Granulomatous Disease (AR-CGD)

Chronic Granulomatous Disease Clinical Trial

Official title: A Phase I/II, Non-Randomized, Open-Label Study of pCCLCHIM-p47 (Lentiviral Vector Transduced CD34+ Cells) in Patients With p47 Autosomal Recessive Chronic Granulomatous Disease (AR-CGD)

Status Enrolling by invitation

Clinical Trial Summary

Background:

Chronic granulomatous disease (CGD) is a genetic disorder. People with CGD are missing a gene that affects their white blood cells. White cells are part of the immune system, and people with GCD are vulnerable to many infections. Researchers want to test a new treatment to replace the missing gene that may be safer than the current treatment for CGD.

Objective:

To test a new type of gene therapy in people with CGD.

Eligibility:

People aged 3 years or older with CGD.

Design:

Participants will undergo apheresis: Blood will be collected through a tube attached to a needle inserted in a vein; the blood will run through a machine that separates certain cells (stem cells); the remaining blood will be returned to the body through a second needle. The participant s stem cells will be modified in a laboratory to add the gene they are missing.

Participants will stay in the hospital for about 40 days.

For the first 10 days, they will undergo many exams, including imaging scans and tests of their heart and lung function. They will receive drugs to prepare their bodies for the gene therapy. They will receive a "central line": A hollow tube will be inserted into a vein in the chest, with a port opening above the skin. This port will be used to draw blood and administer drugs without the need for new needle sticks.

For the gene therapy, each participant s own modified stem cells will be put into their body through the port.

Participants will have 8 follow-up visits over 3 years.

Clinical Trial Description

Study Description:

This is a phase I/II, non-randomized, open-label study of a single infusion of autologous CD34+ cells transduced ex vivo with pCCLCHIM-p47 in 5 patients with p47-AR CGD conditioned with high dose busulfan.

Objectives:

Primary Objectives:

To evaluate the efficacy of pCCLCHIM-p47 transduced autologous CD34+ cells treatment in p47 AR-CGD patients as measured by engraftment of genetically modified cells at 6 months.

Secondary Objectives:

• Safety

• Long term engraftment (assessments at 1 year, 2 years, and 3 years)

• Event Free Survival

• Clinical Efficacy and Health Assessment

Exploratory Objectives:

• Assessment of biomarker utility

• Evaluation of the human microbiome during pCCLCHIM-p47 gene therapy.

• Patient reported assessment of efficacy (QOL)

Endpoints:

Primary Endpoint of this study will be engraftment of genetically modified cells as defined by presence of >10% oxidase positive cells at 6 months.

• Secondary Endpoints will consist of:

• Safety: assessed by recording of the incidence of adverse events.

• Record clinical adverse events and clinically significant laboratory abnormalities.

• Evaluate overall incidence of adverse events for the study as a whole.

• Monitor the incidence of serious adverse events.

• Measure overall survival at 3 years post-transplant

• Assessment of vector safety by vector insertion site analysis (VISA) and replication competent lentivector (RCL) testing.

• Long term multilineage engraftment, as measured by:

• Expression of p47 phox in neutrophils at 6, 12, 18, 24, and 36 months.

• Hematological reconstitution by 90 days post treatment (absolute neutrophil count >500 cells/microliter on three consecutive samples over at least ten days).

• NADPH Oxidase activity in monocytes by dihydrorhodamine (DHR) flow cytometry at 6, 12, 18, 24, and 36 months.

• Percentage of gene modified CD34+ hemopoietic cells in BM at 6, 12, 18, 24, 30, and 36 months as assessed by vector copy number (VCN) qPCR.

• VCN in cell lineages present in PB cells at months 1, 3, 6, 9, 12, 18, 24, and 36.

• Event free Survival

• Resolution of either underlying inflammation and/or infection related to P47 deficiency without recurrence for 3 years.

• Rate of severe (as defined by CTCAE v 5.0 - grade 3 to 5) CGD related infections after withdrawal of antimicrobial prophylaxis in time periods 6-12 and 6-36 months post treatment.

• Assessment of clinical efficacy and health by:

• The nutritional status (height, weight, serum albumin) at 36 months.

• Growth and development of pediatric subjects at 36 months.

• Frequency of severe infections (days requiring IV antibiotics and/or hospitalization for treatment) at 36 months.

• Presence of inflammatory complications (days requiring hospitalizations) at 36 months.

Tertiary Endpoints:

• Utility of Biomarker assessment

• Stool collection for microbiome analysis (optional)

• Patient Quality of life questionnaire collection ;

Related Conditions & MeSH terms

• Chronic Granulomatous Disease
• Granuloma
• Granulomatous Disease, Chronic

• NCT number: NCT06253507
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Enrolling by invitation
• Phase: Phase 1/Phase 2
• Start date: June 26, 2024
• Completion date: March 31, 2027