Phase I/II, Non-randomised, Single-centre, Open-label Study of pCHIM-p47 (Lentiviral Vector Transduced CD34+ Cells) in Patients With p47 Autosomal Recessive Chronic Granulomatous Disease

Status: Recruiting
Location: See location...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 1/Phase 2
SUMMARY

Chronic Granulomatous Disease (CGD) is a rare inherited disorder in which patients suffer from severe infection and inflammation. The first indications of disease usually appear in early childhood. The basic defect has been found to be lie in specialised white blood cells called phagocytic cells, which are responsible for engulfing and destroying germs. In CGD, there is a defect in an enzyme (known as the NADPH-oxidase) that is responsible for generating bleach like substances that are important for killing some important germs. In one form of the disease known as p47 AR-CGD (which accounts for 30% of patients), there are defined mistakes in a gene called NCF1. This gene is needed to form a key component of NADPH-oxidase. In many cases, patients can be protected from infection by constant intake of antibiotics. However, in others potentially life-threatening infections break through. In some cases patients also develop serious inflammation requiring high doses of drugs such as steroids. CGD can be cured by bone marrow transplant and the best results are available when a matched sibling donor is available. Transplant from unmatched donors have a much worse outcome and as a result alternative treatments for patients without a matched donor are highly desirable. Gene therapy of p47 AR-CGD is performed by introducing a normal copy of the human NCF-1 gene into the blood forming stem cells in the patients' bone marrow by using a gene carrier (in this study called a lentiviral vector). After treatment of the bone marrow cells in a specialised laboratory they are given back to the patient and will grow into functional phagocytic cells. There have been no previous clinical trials for patients with p47 AR-CGD however there have been previous gene therapy clinical trials conducted in the UK for patients with the most common form of CGD, known as X-CGD.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 1
Healthy Volunteers: f
View:

• p47 AR-CGD patients \> 23 months of age

• Molecular diagnosis confirmed by Deoxyribonucleic acid (DNA) sequencing and supported by laboratory evidence for absent or reduction \> 95% of the biochemical activity of the NAHPD-oxidase

• At least one prior, ongoing or refractory severe infection and/or inflammatory complications requiring hospitalisation despite conventional therapy

• No 10/10 human leukocyte antigen (HLA)-matched donor available after initial search of National Marrow Donor Program (NMDP) registries performed within the last year

• No co-infection with Human Immunodeficiency Virus (HIV) or hepatitis B virus (HBsAg positive) or hepatitis C virus (HCV ribonucleic acid (RNA) positive), Cytomegalovirus (CMV), adenovirus, parvovirus B 19 or toxoplasmosis

• Written informed consent for adult patient

• Parental/guardian and, where appropriate, child's signed consent/assent

Locations
Other Locations
United Kingdom
Great Ormond Street Hospital
RECRUITING
London
Contact Information
Primary
Karen Oprych
k.gladwin@ucl.ac.uk
0207 7626058
Backup
Ilyas Ali
ilyas.ali@gosh.nhs.uk
Time Frame
Start Date: 2023-03-20
Estimated Completion Date: 2029-04-01
Participants
Target number of participants: 5
Treatments
Experimental: Lentiviral vector transduced CD34+ cells
The investigational product is patient-specific and corresponds to cryopreserved autologous CD34+ cells transduced ex vivo with the pCHIM-p47 vector containing the human p47phox (NCF1) gene in final formulation and container closure system, ready for intended medical use. The starting materials used for the production of the investigational product consist of the viral vector and the patient's CD34+ cells.
Related Therapeutic Areas
Sponsors
Leads: Great Ormond Street Hospital for Children NHS Foundation Trust

This content was sourced from clinicaltrials.gov