P47-Phox, Deficiency ofPhase 1/2NCT05207657
Lentiviral Gene Therapy for p47 AR-CGD
A Phase 1/2 study testing Lentiviral vector transduced CD34+ cells in people with P47-Phox, Deficiency of, run by Great Ormond Street Hospital for Children NHS Foundation Trust at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 23 months and older
- Conditions the study is for
- P47-Phox, Deficiency of
- What is being tested?
- Lentiviral vector transduced CD34+ cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 20 Mar 2023to 1 Apr 2029
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 23 months and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Age ≤ 23 months or > 35 kg body weight
- 10/10 HLA identical (A,B,C,DR,DQ) family or unrelated adult donor unless there is deemed to be an unacceptable risk associated with an allogeneic procedure
- Contraindication for leukapheresis (Haemoglobin <8g/dl, cardiovascular instability, severe coagulopathy)
- Appropriate organ function as outlined below must be observed within 8 weeks of entering this trial.
- Haematologic i) Anaemia (hemoglobin < 8 g/dl). ii) Neutropenia (absolute granulocyte count <1,000/mm3 iii) Thrombocytopenia (platelet count < 150,000/mm3). iv) Prothrombin Time (PT) or Partial thromboplastin time (PTT) > 2 X the upper limits of normal (ULN) (patients with a correctable deficiency controlled on medication will not be excluded).
- Cytogenetic abnormalities known to be associated with haematopoietic defect on peripheral blood or bone marrow.
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- Infectious i) Evidence of infection with HIV-1 and -2, hepatitis B, Hepatitis C, adenovirus, parvovirus B 19 or toxoplasmosis within 8 weeks prior to mobilisation/pheresis or bone marrow harvest. CMV infection is allowable as long as the infection is under control.
- Pulmonary i) Resting O2 saturation by pulse oximetry < 90% on room air. d) Cardiac i) Abnormal electrocardiogram (ECG) indicating cardiac pathology. ii) Uncorrected congenital cardiac malformation with clinical symptomatology. iii) Active cardiac disease, including clinical evidence of congestive heart failure, cyanosis, iv) Hypotension. v) Poor cardiac function as evidenced by Left Ventricular Ejection Fraction (LVEF) < 40% on echocardiogram.
- Neurologic i) Significant neurologic abnormality by examination. ii) Uncontrolled seizure disorder. f) Renal i) Renal insufficiency: serum creatinine greater than or equal to 1.5 mg/dl, or greater than or equal to 3+ proteinuria ii) Abnormal serum sodium, potassium, calcium, magnesium at grade III or IV according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 g) Hepatic/GI: i) Serum transaminases > 5X the upper limit of normal (ULN). ii) Serum Bilirubin > 2X ULN. iii) Serum Glucose > 1.5x ULN. h) Oncologic i) Evidence of active malignant disease
- General
- Expected survival < 6 months.
- Major congenital anomaly.
- Ineligible for autologous Haematopoietic Stem Cell Transplant (HSCT) by the criteria at the clinical site.
- Contraindication for administration of conditioning medication
- Known sensitivity to Busulfan
- Administration of gamma-interferon within 30 days before the infusion of transduced, autologous CD34+ cells
- Participation in another experimental therapeutic protocol within 6 months prior to baseline and during the study period
- Any other condition that, in the opinion of the Investigator, may compromise the safety or compliance of the patient or would preclude the patient from successful study completion
- Patient/Parent/Guardian unable or unwilling to comply with the protocol requirements.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Ilyas Ali contact
United Kingdom1 site, 1 recruiting
- Recruiting
Great Ormond Street Hospital
London, WC1N 3JH
Claire Booth, 0207 905 2198, c.booth@ucl.ac.uk
Karen Oprych, k.gladwin@ucl.ac.uk
About this study
Official title: 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
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.
- Conditions
- P47-Phox, Deficiency of
- Being tested
- Lentiviral vector transduced CD34+ cells
- Medical subject headings
- Granulomatous Disease, Chronic, Autosomal Recessive, Cytochrome B-Positive, Type I
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lentiviral vector transduced CD34+ cellsDrug
Also called p47LV transduced autologous CD34+ cells
Gene therapy for p47 AR-CGD will be performed by introduction a normal copy of the NCF-1 gene into the blood forming stem cells (CD34+ cells) of the patient's bone marrow by using a type of gene delivery system (in this trial called a lentiviral vector). The gene corrected cells are then transplanted back into the patient
| Study group | Role | What they receive |
|---|---|---|
| Lentiviral vector transduced CD34+ cells | Experimental | 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. Receives: Drug: Lentiviral vector transduced CD34+ cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the safety of p47 LV transduced autologous CD34+ cells treatment in p47 AR-CGD patients.
The safety will be measure by:
- Safety of the gene therapy procedure will be assessed through evaluation of adverse reactions after infusion and adverse reactions observed by the investigator or reported by the patient/parent/guardian during the study period.
- As part of the overall safety evaluation, analysis of the lentivirus integration sites will be performed in different cell subpopulations and to investigate specific clonal expansions. Quantification of transgene copy numbers is determined on sorted cell populations by ddPCR methodology.
Measured: 6 months to 1 year
To evaluate the efficacy of p47 LV transduced autologous CD34+ cells treatment in p47 AR-CGD patients.
Failure of gene therapy is defined by the absence of the NCF1 functioning granulocytes assessed by a DHR test (< 5% of expressing cells) 12 months after the procedure.
Measured: 6 months to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2022
- Study start20 Mar 2023
- Primary completion1 Apr 2029 (estimated)
- Study completion1 Apr 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for P47-Phox, Deficiency ofStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Great Ormond Street Hospital for Children NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Claire Booth, Principal investigator, UCL Great Ormond Street Institute of Child Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05207657
- Sponsor's protocol ID
- 19IC05
- Status last verified
- Mar 2023
- First submitted
- 24 Jun 2021
- Last updated
- 16 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05207657
- Acronym / sponsor ID
- 19IC05
- Conditions
- P47-Phox, Deficiency of
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 5 participants (estimated)
- Lead sponsor
- Great Ormond Street Hospital for Children NHS Foundation TrustUniversity, hospital or other
- Study start
- 20 Mar 2023 (actual)
- Primary completion
- 1 Apr 2029 (estimated)
- Study completion
- 1 Apr 2029 (estimated)
- First posted
- 26 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lentiviral vector transduced CD34+ cells | Experimental | Drug: Lentiviral vector transduced CD34+ cellsThe 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. |
Who may qualify
- Ages
- 23 months and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (19 listed)
- Age ≤ 23 months or > 35 kg body weight
- 10/10 HLA identical (A,B,C,DR,DQ) family or unrelated adult donor unless there is deemed to be an unacceptable risk associated with an allogeneic procedure
- Contraindication for leukapheresis (Haemoglobin <8g/dl, cardiovascular instability, severe coagulopathy)
- Appropriate organ function as outlined below must be observed within 8 weeks of entering this trial.
- General
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lentiviral vector transduced CD34+ cellsAlso: p47LV transduced autologous CD34+ cellsGene therapy for p47 AR-CGD will be performed by introduction a normal copy of the NCF-1 gene into the blood forming stem cells (CD34+ cells) of the patient's bone marrow by using a type of gene delivery system (in this trial called a lentiviral vector). The gene corrected cells are then transplanted back into the patient | Drug | Lentiviral vector transduced CD34+ cells |
Primary outcome
To evaluate the safety of p47 LV transduced autologous CD34+ cells treatment in p47 AR-CGD patients.
Time frame: 6 months to 1 year
The safety will be measure by: * Safety of the gene therapy procedure will be assessed through evaluation of adverse reactions after infusion and adverse reactions observed by the investigator or reported by the patient/parent/guardian during the study period. * As part of the overall safety evaluation, analysis of the lentivirus integration sites will be performed in different cell subpopulations and to investigate specific clonal expansions. Quantification of transgene copy numbers is determined on sorted cell populations by ddPCR methodology.
To evaluate the efficacy of p47 LV transduced autologous CD34+ cells treatment in p47 AR-CGD patients.
Time frame: 6 months to 1 year
Failure of gene therapy is defined by the absence of the NCF1 functioning granulocytes assessed by a DHR test (< 5% of expressing cells) 12 months after the procedure.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2023.
- Individual participant dataSharing planned: No
Related trials for P47-Phox, Deficiency of
Enrolling by invitationPhase 1/2
pCCLCHIM-p47 (Lentiviral Vector Transduced CD34 Plus Cells) in Patients With p47 Autosomal Recessive Chronic Granulomatous Disease (AR-CGD)
p47, Autosomal Recessive
RecruitingPhase 1/2
Open-label Gene Therapy Study in p47-CGD
Chronic Granulomatous Disease (CGD)
Enrolling by invitationPhase 1/2
A Study of the Safety and Efficacy of Prime Editing (PM359) in Participants With p47phox Autosomal Recessive Chronic Granulomatous Disease (CGD )
Chronic Granulomatous Disease, Granulomatous Disease, Chronic
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ilyas Ali contact
Claire Booth principal investigator
UCL Great Ormond Street Institute of Child Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Lentiviral vector transduced CD34+ cells in people with P47-Phox, Deficiency of, run by Great Ormond Street Hospital for Children NHS Foundation Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 16 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Karen Oprych (0207 7626058, k.gladwin@ucl.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To evaluate the safety of p47 LV transduced autologous CD34+ cells treatment in p47 AR-CGD patients. (time frame: 6 months to 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2023.