NCT05207657

Lentiviral Gene Therapy for p47 AR-CGD

Recruiting now Phase 1, PHASE2 Last updated 16 May 2023

What this trial tests

Phase 1, PHASE2 trial testing Lentiviral vector transduced CD34+ cells in P47-Phox, Deficiency of in 5 participants. Currently enrolling.

Timeline

20 March 2023

Primary endpoint
1 April 2029

1 April 2029

Quick facts

Lead sponsor	Great Ormond Street Hospital for Children NHS Foundation Trust
Phase	Phase 1, PHASE2
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	5
Start date	20 March 2023
Primary completion	1 April 2029
Estimated completion	1 April 2029
Sites	1 location across United Kingdom

Drugs / interventions tested

• Lentiviral vector transduced CD34+ cells — full drug profile →

Conditions studied

• P47-Phox, Deficiency of — all drugs for P47-Phox, Deficiency of →

Sponsor

Great Ormond Street Hospital for Children NHS Foundation Trust

Who can join

23 Months and older, any sex, with P47-Phox, Deficiency of. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

1. Advances in gene therapy for inborn errors of immunity.
   Ott de Bruin LM, Lankester AC, Staal FJT. · · 2023 · cited 17× · PMID 37846903 · DOI 10.1097/aci.0000000000000952
2. Precision medicine: The use of tailored therapy in primary immunodeficiencies.
   Pinto MV, Neves JF. · · 2022 · cited 11× · PMID 36569887 · DOI 10.3389/fimmu.2022.1029560
3. Haematopoietic Stem Cell Transplantation for Chronic Granulomatous Disease.
   Slatter MA, Gennery AR. · · 2023 · cited 10× · PMID 37763024 · DOI 10.3390/jcm12186083
4. Clinical hematopoietic stem cell-based gene therapy.
   John T, Czechowicz A. · · 2025 · cited 6× · PMID 40285354 · DOI 10.1016/j.ymthe.2025.04.029
5. A Comprehensive Review of IL-10 and IL-10 Receptor Deficiencies: From Basic Science to Clinical Bedside.
   Xiao J, Ye Z, Huang Y. · · 2026 · PMID 41888292 · DOI 10.1007/s12016-026-09154-6
6. Gene therapy for inborn errors of immunity: past progress, current status and future directions.
   Torrance R, Orf K, Fox TA. · · 2025 · PMID 41693912 · DOI 10.20517/rdodj.2025.42