Clinical trials

Clinical trials are biomedical or health-related research studies in human beings that follow a highly regulated, pre-defined procedure. they may help assess the effectiveness of a drug to treat a disease, test a new therapy, a new surgical procedure or medical device. For example clinical trials have been used to assess the effectiveness and safety of anti-fungal treatments for CGD. They may also be a longer-term observational study to understand more about the long-term implications of having a disease. The aim of clinical trials is to help improve healthcare.

Clinical trials can take place only after extensive studies in the laboratory have been done.

High quality information confirming the potential of a new treatment to help patients must be presented, scrutinised and approved by the appropriate regulatory authority in the country where the trial is taking place.

In the UK and Europe, the law governs clinical trials with standards set by the European Union Clinical Trials Directive.

In the UK trials are regulated by the Medicines and Healthcare Products Regulatory Agency although other ethical boards and authorities may be additionally involved.

In the USA, clinical trials are regulated by the Food and Drug Administration (FDA).

Clinicians and researchers MUST obtain the full and informed consent of participating human subjects and when appropriate the permission of a parent or legal guardian if a child is involved.

Anyone considering whether or not to take part in a clinical trial should be advised about the potential risks and benefits of participating before they make their decision. They must also be free to withdraw from the trial at any time without prejudicing their future medical care.

A registry of approved clinical trials from around the world is available at http://clinicaltrials.gov/

General information on clinical trials is available at http://www.bbc.co.uk/health/physical_health/conditions/clinical_trials.shtml

Information on clinical trials for bone marrow transplantation is available at http://www.nhs.uk/Conditions/Bone-marrow-transplant

The list below gives details of clinical trials from around the world for CGD that are currently listed as being active on clinical trial registers. The list is not exhaustive.  Some clinical trials may be specific to CGD. Other trials, especially those associated with stem cell transplantation may involve CGD patients and patients with other genetic conditions. Regardless of the geographical location of the trial the results will help improve healthcare for those affected by CGD.

Clinical trials in the UK

Study title: Gene Therapy for P47 AR- Chronic Granulomatous Disorder

Institution: Great Ormond Street for Children NHS Foundation Trust

Aim: Great Ormond Street Hospital has announced the opening of the p47 CGD research trial. The aim for this clinical trial is to use gene therapy to transfer a normal copy of the p47 gene into the bone marrow of children with p47 CGD to correct the gene defect. The trial is specifically intended for children over 6 months old who have experienced severe CGD-related infections or inflammatory complications that have needed hospitalisation, and who do not have a matched sibling donor. If you are interested in learning more, you are invited to contact the trial team at Jinhua.Xu-Bayford@gosh.nhs.uk”

Link: Lentiviral Gene Therapy for p47 AR-CGD – Full Text View – ClinicalTrials.gov

Study title: Gene Therapy for X-linked Chronic Granulomatous Disease (X-CGD)

Institution: University College London Hospital (UCLH) London, University College London Hospital (UCLH) and Great Ormond Street Hospital, London.

Aim: This gene therapy trial uses the latest lentiviral gene reagent, developed with the help of funding from CGDS, to transfer a normal copy of human gp91-phox gene into the blood forming stem cells of patients’ bone marrow to correct the genetic defect. This trial is active but not recruiting.

Link: https://ichgcp.net/clinical-trials-registry/NCT01855685

Clinical trials in the rest of the world

Study Title: Gene Therapy using Prime Editing (PM359) for P47 Autosomal Recessive Chronic Granulomatous Disease

Institution: University College of London Hospital

Aim: This is an open-label, single-arm, multicenter Phase 1/2 study evaluating the safety and efficacy of gene therapy by transplantation of Prime Edited autologous CD34+ stem cells modified ex vivo (PM359 – Drug Product) in participants with autosomal recessive CGD caused by mutations in the NCF1 (Neutrophil Cytosolic Factor 1) gene. PM359 is administered as a one-time infusion. Link: https://clinicaltrials.gov/study/NCT06559176

Study title: Fecal Microbiota Transplantation for Chronic Granulomatous Disease-Associated Colitis

Institution: National Institute of Allergy and Infectious Diseases, USA.

Aim: To see if FMT can reduce inflammation in the colon.

Estimated study start time: June 21, 2022

Estimated primary completion date: July 1, 2024

Estimated study completion date: March 1, 2025

Link: https://clinicaltrials.gov/ct2/show/NCT05333471

Gene Therapy

 

Study title: Gene Therapy for X-linked Chronic Granulomatous Disease

Institution: Hôpital Necker Enfants Malades, Paris, France.

Aim: To test the safety and efficacy of a lentiviral vector to treat people with X-linked CGD. This trial is active but not recruiting.

Link: https://ichgcp.net/clinical-trials-registry/NCT02757911

Study title: Study of Gene Therapy Using a Lentiviral Vector to Treat X-linked Chronic Granulomatous Disease

Institution: University of California, Los Angeles, USA.

Aim: This trial uses a 3rd generation self-inactivating lentiviral vector which directs gp91phox expression in cells of the myeloid lineage which includes neutrophils, the cells affected in CGD. This trial is active but not recruiting.

Link: https://ichgcp.net/clinical-trials-registry/NCT02234934

Study title: Lentiviral Gene Therapy in CGD

Institution: Shenzhen Geno-Immune Medical Institute, China.

Aim: To evaluate the safety of the advanced self-inactivating lentiviral vector TYF-gp91phox and TYF-p47phox and the efficacy of immune reconstitution in patients overcoming frequent infections present at the time of treatment, assessment of vector integration sites, and finally the long-term correction of immune dysfunctions.

Link: https://clinicaltrials.gov/ct2/show/NCT03645486

Bone Marrow Transplantation

 

Study title: Haploidentical Transplant for People With CGD Using Alemtuzumab, Busulfan and TBI With Post-Transplant Cyclophosphamide

Institution: National Institutes of Health Clinical Center, Bethesda, Maryland, USA.

Aim: To see if it is safe to use a related bone marrow donor who is only a partial match to a person with CGD. To see how well drugs given to a person before and after transplant help the body accept the transplant.

Link: https://clinicaltrials.gov/ct2/show/NCT03910452

Study title: High Dose Peripheral Blood Stem Cell Transplantation With Post Transplant Cyclophosphamide for Patients With CGD

Institution: National Institutes of Health Clinical Center, Bethesda, Maryland, USA.

Aim: To determine engraftment rates with the use of high cell doses, without increasing the risk of GvHD by using post- transplant cyclophosphamide and sirolimus in conjunction with a busulfan- based conditioning regimen.

Link: https://clinicaltrials.gov/ct2/show/NCT02629120

Study title: Plerixafor/G-CSF as Additional Agents for Conditioning Before HSCT in CGD Patients

Institution: Federal Research Institute of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.

Aim: To evaluate the safety and efficiency of myeloablative conditioning with Plerixafor and G-CSF as additional agents for prevention of graft failure after stem cell transplantation in patients with CGD.

Link: https://clinicaltrials.gov/ct2/show/NCT03547830

Study title: A Study of Hematopoietic Stem Cell Transplantation (HSCT) in Immune Function Disorders Using a Reduced Intensity Preparatory Regime

Institution: Washington University School of Medicine and Methodist Heathcare
San Antonio, Texas, USA.

Aim: To study the use of reduced intensity conditioning for BMT to reduce graft rejection and optimize donor cell engraftment.

Link: https://clinicaltrials.gov/ct2/show/NCT01821781

Study title: HLA Matched Unrelated or Non-Genotype Identical Related Donor Transplantation For CGD.

Institution: USA – Baylor College of Medicine, Houston, Texas.

Aim: To test a procedure to improve donor cell engraftment and the prevention of graft versus host disease (GVHD) in CGD. Patients will be treated with Campath (Alemtuzumab), an antibody directed against a marker that is present on most lymphocytes. Campath has been shown to be effective as an immunosuppressive drug, helping the process of donor grafts and preventing GVHD.

Link: http://clinicaltrials.gov/ct2/show/NCT00578643

Study title: Treosulfan and Fludarabine Before Donor Stem Cell Transplant in Treating Patients With Nonmalignant Inherited Disorders.

Institution: USA – Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Recruiting Seattle, Washington, USA.

Aim: This study is investigating whether a new conditioning regimen that uses less intensive drugs (treosulfan and fludarabine) results in engraftment of new donor cells without increased toxic effects in patients after transplant.

Link: http://clinicaltrials.gov/ct2/show/NCT00919503

Study title: Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies

Institution:  Masonic Cancer Center, University of Minnesota, USA.

Aim: To study outcomes of BMT for a range of primary immune conditions, including CGD.

Link: https://clinicaltrials.gov/ct2/show/record/NCT01652092

Treatments for CGD

 

Study title: Role of Interferon-gamma 1-b (IFN-γ) on Cells of the Innate Immune System: Functional, Biochemical and Gene Expression Studies in Patients With CGD

Institution: University of Colorado Anschutz Medical Campus, Colorada, United States.

Aim: To study changes in neutrophil bacterialcidal activity in patients with CGD on standard treatment schedule and dose of IFN-γ in comparison to results for the patients off IFN-γ.

Link: https://clinicaltrials.gov/ct2/show/record/NCT03548818

Study title: Vitamin D3 For CGD Patients With BCGosis/Itis

Institution: Children’s Hospital of Fudan University, China.

Aim: To study vitamin D supplementation to treat BCG infection.

Link: https://clinicaltrials.gov/ct2/show/NCT03984890

Long term outcome studies

 

Study title: Natural History of Intestinal Inflammation in Patients With Primary Immune Dysregulations

Institution: National Institutes of Health Clinical Center, Bethesda, Maryland, USA.

Aim: To learn more about when and why inflammatory bowel disease may develop in some people with primary immune deficiency.

Link: https://clinicaltrials.gov/ct2/show/study/NCT03278912

Study title: Analysis of Patients Treated for CGD

Institution: National Institute of Allergy and Infectious Diseases (NIAID), Maryland, USA.

Aim: A longitudinal study (e.g., looking at information of participants over time) to allow doctors to better understand the outcomes of different therapeutic approaches and to best design new treatments and clinical trials in the future for children with CGD.

Link:  https://clinicaltrials.gov/ct2/show/NCT02082353

Study title: Evaluation of Patients With Immune Function Abnormalities

Institution: National Institutes of Health Clinical Center, Bethesda, Maryland, USA.)

Aim:  A comprehensive study of the pathophysiology of CGD to understand the underlying mechanisms of inflammation and infection.

Link: https://clinicaltrials.gov/ct2/show/NCT00128973

Study title: Non-Invasive Assessment of Atherosclerosis in Patients With CGD and Other Disorders of the Immune System.

Institution: National Institutes of Health Clinical Center, Bethesda, Maryland, USA.

Aim: This study will test the theory that patients with CGD may be protected from developing atherosclerosis, hardening of the arteries, due to reduced superoxide and other ROS production by phagocytic cells.  Atherosclerosis is a major cause of heart disease. Participants will be contacted every 2 years in the future for up to 30 years to determine whether they have developed heart disease. The aim is to determine the prevalence of atherosclerosis in CGD and other patients with in-born disorders of the immune system as compared to the normal healthy population.

Link: http://clinicaltrials.gov/ct2/show/NCT01063309

Study title: Detection and Characterization of Infections and Infection Susceptibility.

Institution: National Institutes of Health Clinical Center, Bethesda, Maryland, USA.

Aim: This is an observational study to examine the causes of immune disorders affecting white blood cells, which defend against infections. The study will seek to develop better means of diagnosis and treatment of these immune disorders.

Link: http://clinicaltrials.gov/ct2/show/NCT00404560