Chronic Granulomatous Disease (CGD)Phase 1/2NCT06325709
Base Editing for Mutation Repair in Hematopoietic Stem & Progenitor Cells for X-Linked Chronic Granulomatous Disease
A Phase 1/2 study testing Campath, Sirolimus and Base-edited hematopoietic stem and progenitor cells in people with Chronic Granulomatous Disease (CGD) and X-Linked Chronic Granulomatous Disease, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
Background: Chronic granulomatous disease (CGD) is a rare immune disorder caused by a mutation in the CYBB gene. People with CGD have white blood cells that do not work properly and are at greater risk of getting infections. Read more about this study
- Who is it for?
- Ages 18 to 75 years, men only
- Conditions the study is for
- Chronic Granulomatous Disease (CGD), X-Linked Chronic Granulomatous Disease
- What is being tested?
- Campath, Sirolimus and Base-edited hematopoietic stem and progenitor cells
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Apr 2024to 31 Dec 2032
- 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 18 to 75 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ->= 18 years of age.
- Confirmed CYBB c.676 C>T mutation.
- Male patients.
- Clinically stable and eligible to undergo apheresis and conditioning chemotherapy.
- ->=5 x 10^6 cryopreserved cells/kg body weight available for study product manufacturing.
- History of at least one prior serious infection or inflammatory complication requiring hospitalization despite conventional therapy.
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- In the experience of a qualified clinical investigator, the patient has a poor prognosis.
- Able and willing to use a highly effective method of contraception, AND partner has communicated her willingness through subject to do same, if engaging in potentially reproductive sex from the signing of the informed consent and for 6 months after IMP infusion. Acceptable methods of contraception include the following:
- Hormonal contraception in continuously effective use by female partner.
- Male or female condom with spermicide as indicated.
- Diaphragm or cervical cap in consistent and effective pattern of use with a spermicide by female partner.
- Intrauterine device in-situ throughout above period by female partner.
Who cannot join
- Individuals meeting any of the following criteria will be excluded from study participation:
- Untreated, acute infection.
- Elevated anti-gp91 specific autoantibodies >2 x ULN
- Elevated anti-gp91 specific T cells (>10 fold)
- Anti-platelet antibody screening with >1 anti-platelet antibody positive in the presence of an ongoing brain infection; OR >1 anti-platelet antibody positive and considered unsafe for study participation after consultation with hematology specialist.
- Known hypersensitivity to busulfan or any component of the product.
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- Contraindications for administration of busulfan.
- Any current or pre-existing hematologic malignancy.
- Chronic infections that are considered unsafe for participation in the study by Infectious Disease Consultant.
- Cardiac abnormalities and neurological abnormalities that are deemed unsafe to participate in the study.
- Childhood malignancy (occurring before 18 years of age) in the patient or a first degree relative, or previously diagnosed known genotype of the participant conferring a predisposition to cancer (no DNA or other testing for cancer predisposition genes will be performed as part of the screen for this protocol).
- Hematological parameters unsafe for apheresis or above Grade 2 Common Terminology Criteria for Adverse Events (CTCAE) criteria until improved.
- Hepatic dysfunction- alanine aminotransferase (ALT >3.0 - 5.0 x upper limit of normal [ULN]), aspartate aminotransferase (AST >3.0 - 5.0 x ULN), bilirubin (>1.5 - 3.0 x ULN).
- Renal dysfunction-serum creatinine >1.5 - 3.0 x ULN or creatinine clearance 59-30 mL/min/1.73 m^2.
- Coagulation dysfunction- Prothrombin INR or Partial thromboplastin time >2 x ULN (patients on controlled anticoagulation agents will not be excluded for therapeutic levels).
- Uncontrolled hypertension- Systolic BP 140-159 mm Hg or diastolic BP 90-99 mm Hg.
- Abnormal blood chemistries- Hyperkalemia (K >5.5 - 6.0 mmol/L), Hypokalemia (<LLN - 3.0 mmol/L and requiring intervention); OR Hypercalcemia (corrected serum calcium >11.5 - 12.5 mg/dL), Hypocalcemia (corrected serum calcium <8.0 -7.0 mg/dL)
- These values exclude false abnormalities secondary to hemolysis.
- Cytogenetic abnormalities evidenced on bone marrow aspirate.
- Pulmonary dysfunction FEV1<25% predicted.
- Previous treatment with gene therapy or gene editing products.
- Previous receipt of non-HLA matched donor granulocyte transfusions.
- Any other condition that, in the opinion of the investigator, may unduly compromise the safety or compliance of the patient, or would make successful study completion highly unlikely.
- Unwilling to submit their information as part of the alemtuzumab (Campath(R)) Distribution Program application or the Distribution Program committee has determined the participant is not qualified to receive alemtuzumab.
- NOTE: Alemtuzumab (campath) is no longer distributed commercially. To receive product, the physician must contact the program for the participant. If the participant is not willing to consent to submit their info (demographics, contact information, and rationale for use) to the program such that we can obtain the drug, then we cannot proceed with conditioning; therefore, no gene therapy will occur on this protocol.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
NIH Clinical Center Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY dial 711, ccopr@nih.gov
Suk See De Ravin, MD, (301) 496-6772, sderavin@mail.nih.gov
About this study
Official title: Phase 1/2 Trial of Base Editing for Mutation Repair in Hematopoietic Stem & Progenitor Cells for X-linked Chronic Granulomatous Disease
Background:
Chronic granulomatous disease (CGD) is a rare immune disorder caused by a mutation in the CYBB gene. People with CGD have white blood cells that do not work properly and are at greater risk of getting infections. Researchers want to know if gene therapy using the patient's own base-edited stem cells can improve the white cells' functioning and result in fewer CGD-related infections.
Read more
Objective:
To learn if base-edited stem cells will correct the white blood cells in people with CGD.
Eligibility:
Males aged 18 years and older with X-linked CGD.
Design:
This is a non-randomized study. Participants with the specific mutation under study will be screened during the initial phase.
During the development phase, participants will undergo apheresis to collect stem cells for base-editing correction of the mutation.
During the treatment phase, participants will first receive Campath (alemtuzumab) to reduce the risk of an immune response to the new protein expressed by the base-edited cells. This will be followed by conditioning chemotherapy with busulfan and subsequent infusion of the base-edited stem cells. Participants will be maintained on sirolimus to further reduce the risk of an immune response to the new protein expressed by the base-edited cells.
Follow-up visits will continue for 15 years.
Read the detailed description
Study Description:
Open-label, phase 1/2 trial to determine the safety, and efficacy of a single infusion of base-edited (BE) autologous hematopoietic stem and progenitor cells (HSPCs) for treatment of X-linked chronic granulomatous disease (X-CGD). Base editing is performed to repair CYBB missense gene mutations (eg, CYBB c.676C>T). The study hypotheses are that 1) base editing can efficiently repair gene mutations in HSPCs; and 2) BE HSPCs can engraft and differentiate into functional phagocytes with restored nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity.
During the initial development phase each study participant will undergo apheresis for CD34+ HSPC collection for the development and validation of a mutation-specific BE system.
During the treatment phase, participants will receive a one-time infusion of the BE autologous HSPC (study product) after the administration of Campath (alemtuzumab) and of busulfan conditioning (total 12 mg/kg with a targeted total AUC of 65,000 ng/mL x hr). Sirolimus will be initiated on Day -1 and may be given for approximately 3-6 months.
Participants will have follow-up evaluations at months 3, 6, 12, 18, and 24, and yearly thereafter until 5 years after treatment. Key study assessments include adverse event (AE) assessment, blood laboratory evaluations of functional protein made from the target gene (CYBB, encodes for gp91^phox), and deoxyribonucleic acid (DNA) sequencing to identify rates of gene repair and off-target mutation.
The final study follow-up under this protocol will be at 5 years, but long-term follow-up under a separate NIH protocol will continue annually to 15 years after treatment.
Objectives:
Primary Objectives:
- To evaluate the safety of BE autologous CD34+ cells.
- To evaluate the efficacy of BE autologous CD34+ cells.
Secondary Objectives:
-To evaluate:
- Efficiency of base editing (percentages of target nucleotide conversion).
- Engraftment capability of BE HSPCs.
- Efficiency in restoring gp91^phox expression
- Efficiency in restoring NADPH oxidase function.
- Clinical efficacy.
- Stability of gene correction.
Exploratory Objectives:
-To evaluate:
- Specificity of base editing by assessing rates of off-target edits at top predicted sites.
- Random off-target edits by whole genome sequencing (WGS).
Endpoints:
Primary Endpoints:
- Safety of gene therapy using BE autologous HSPCs as measured by study product-related AEs and serious AEs (SAEs) through 2 years after treatment.
- Efficacy of gene therapy determined as percentages of subjects who have >= 10% oxidase-positive granulocytes at 12 months after infusion.
Secondary Endpoints:
- Determine frequency of converted target nucleotide alleles.
- Assess the frequency of gene-modified alleles compared to infusion product in peripheral blood at 12 months.
- Evaluate efficacy of restoring gp91^phox expression.
- Evaluate efficacy of NADPH oxidase functional restoration as measured by the dihydrorhodamine (DHR) flow cytometry oxidase assay at 12 months after treatment (>=10% oxidase-positive neutrophils), or by quantitative measurement of reactive oxygen species (ROS) using the ferricytochrome C assay on peripheral blood granulocytes.
- Evaluate clinical benefit by improvement of baseline clinical problems such as recurrent infections, growth failure, malnutrition, inflammatory bowel disease, or antibiotic usage.
- Assess stability of gene correction by serial measurement of percent of nucleotide-converted alleles.
Exploratory Endpoints:
- Evaluate specificity by assessing for off-target edits at predicted sites with high-throughput sequencing of the 5 most common candidate off-target loci identified by a comprehensive in vitro screen, Circularization for High-throughput Analysis of Nuclease Genome-wide Effects by sequencing (CHANGE-seq-BE), in peripheral blood cells.
- Determine rate of random off-target edits WGS.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CampathDrug
Immunomodulating agent: Daily subcutaneous administration beginning Day -9 for 5 days to reduce the risk of an immune response to the protein expressed by the BE HSPCs.
SirolimusDrug
Immunomodulating agent: Daily oral dosing beginning Day -1 for approximately 3 to 6 months to reduce the risk of an immune response to the protein expressed by the BE HSPCs.
Base-edited hematopoietic stem and progenitor cellsBiological
Investigational/Study Agent: Base-edited autologous CD34 plus hematopoietic stem and progenitor cell product. The product is administered intravenously as a single infusion. This product is under an IND.
BusulfanDrug
Transplant Conditioning Agent: An alkylating chemotherapy drug to enhance engraftment of the study agent (base-edited stem cells). Conditioning will be given intravenously over 3 days with an approximate total dose of 12mg/kg. Drug levels obtained will be obtained to achieve the targeted total busulfan AUC of 65,000 ng/mL x hr.
PaliferminDrug
Mucositis Prophylaxis Agent: Intravenous infusion of keratinocyte growth factor (Palifermin) at 60 mcg/kg/day before (Days -7 to Day -5 administration of busulfan and (Days 1 to 3) post-busulfan administration to prevent oral mucositis.
FilgrastimDrug
Stem Cell Mobilizing Agent: Subcutaneous administration for 6 consecutive days. It is necessary to mobilize stem cells for collection.
PlerixaforDrug
Stem Cell Mobilizing Agent: Subcutaneous administration for 2 consecutive days to improve stem cell collection.
| Study group | Role | What they receive |
|---|---|---|
| Single Arm Study | Experimental | Not described Receives: Drug: Campath; Drug: Sirolimus; Biological: Base-edited hematopoietic stem and progenitor cells; Drug: Busulfan; Drug: Palifermin; Drug: Filgrastim; Drug: Plerixafor |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the safety of base-edited autologous CD34+ cells
Safety of gene therapy using base-edited autologous hematopoietic stem and progenitor cells as measured by study agent related adverse events and serious adverse events
Measured: Initiated from the time of the infusion of base-edited cells through 2 years post-infusion
To evaluate the efficacy of base-edited autologous CD34+ cells
Efficacy of gene therapy as determined by percentages ofparticipants who have >= 10 percent oxidase-positive granulocytes
Measured: Assessed 12 months post-infusion of base-edited cells
Secondary outcomes (6)
Evaluate the efficiency of base-editing.
Measure the percentages of gp91-expressing cells
Measured: Assessed 12-24 months post-infusion of base-edited cells
Evaluate the engraftment capability of base-edited hematopoietic stem progenitor cells.
Measure the percentages of edited myeloid cells
Measured: Assessed 12-24 months post-infusion of base-edited cells
Evaluate the efficiency in restoring gp91phox expression.
Measure the frequency of gp91phox+ cells and the amount of gp91phox protein
Measured: Assessed 12-24 months post-infusion of base-edited cells
Evaluate efficacy in restoring NADPH oxidase function.
Measure the frequency of DHR+ cells
Measured: Assessed 12-24 months post-infusion of base-edited cells
Evaluate clinical efficacy
Assess the frequency of infections and progression of co-morbidities of CGD
Measured: Assessed through study completion
Evaluate the stability of gene correction
Compare frequencies of corrected alleles before infusion and at study completion
Measured: Assessed through study completion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2024
- Study start17 Apr 2024
- Primary completion31 Dec 2032 (estimated)
- Study completion31 Dec 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Chronic Granulomatous Disease (CGD)Studies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- 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
- 15 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Suk S De Ravin, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06325709
- Sponsor's protocol ID
- 10001580
- Other IDs
- 001580-I
- Status last verified
- 29 Jul 2026
- First submitted
- 21 Mar 2024
- Last updated
- 5 Nov 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Komor AC, Badran AH, Liu DR. Editing the Genome Without Double-Stranded DNA Breaks. ACS Chem Biol. 2018 Feb 16;13(2):383-388. doi: 10.1021/acschembio.7b00710. Epub 2017 Oct 9.
PubMed 28957631Kuhns DB, Alvord WG, Heller T, Feld JJ, Pike KM, Marciano BE, Uzel G, DeRavin SS, Priel DA, Soule BP, Zarember KA, Malech HL, Holland SM, Gallin JI. Residual NADPH oxidase and survival in chronic granulomatous disease. N Engl J Med. 2010 Dec 30;363(27):2600-10. doi: 10.1056/NEJMoa1007097.
PubMed 21190454Bzhilyanskaya V, Ma L, Liu S, Fox LR, Whittaker MN, Meis RJ, Choi U, Lawson A, Ma M, Theobald N, Burkett S, Sweeney CL, Lazzarotto CR, Tsai SQ, Lack JB, Wu X, Dahl GA, Malech HL, Kleinstiver BP, De Ravin SS. High-fidelity PAMless base editing of hematopoietic stem cells to treat chronic granulomatous disease. Sci Transl Med. 2024 Oct 16;16(769):eadj6779. doi: 10.1126/scitranslmed.adj6779. Epub 2024 Oct 16.
PubMed 39413163
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1/2 Trial of Base Editing for Mutation Repair in Hematopoietic Stem & Progenitor Cells for X-linked Chronic Granulomatous Disease
- ClinicalTrials.gov ID
- NCT06325709
- Acronym / sponsor ID
- 10001580
- Keywords
- base editing, Gene Editing
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 17 Apr 2024 (actual)
- Primary completion
- 31 Dec 2032 (estimated)
- Study completion
- 31 Dec 2032 (estimated)
- First posted
- 22 Mar 2024 (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.
Background:
Chronic granulomatous disease (CGD) is a rare immune disorder caused by a mutation in the CYBB gene. People with CGD have white blood cells that do not work properly and are at greater risk of getting infections. Researchers want to know if gene therapy using the patient's own base-edited stem cells can improve the white cells' functioning and result in fewer CGD-related infections.
Objective:
To learn if base-edited stem cells will correct the white blood cells in people with CGD.
Eligibility:
Males aged 18 years and older with X-linked CGD.
Design:
This is a non-randomized study. Participants with the specific mutation under study will be screened during the initial phase.
During the development phase, participants will undergo apheresis to collect stem cells for base-editing correction of the mutation.
During the treatment phase, participants will first receive Campath (alemtuzumab) to reduce the risk of an immune response to the new protein expressed by the base-edited cells. This will be followed by conditioning chemotherapy with busulfan and subsequent infusion of the base-edited stem cells. Participants will be maintained on sirolimus to further reduce the risk of an immune response to the new protein expressed by the base-edited cells.
Follow-up visits will continue for 15 years.
Detailed description
Study Description:
Open-label, phase 1/2 trial to determine the safety, and efficacy of a single infusion of base-edited (BE) autologous hematopoietic stem and progenitor cells (HSPCs) for treatment of X-linked chronic granulomatous disease (X-CGD). Base editing is performed to repair CYBB missense gene mutations (eg, CYBB c.676C>T). The study hypotheses are that 1) base editing can efficiently repair gene mutations in HSPCs; and 2) BE HSPCs can engraft and differentiate into functional phagocytes with restored nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity.
During the initial development phase each study participant will undergo apheresis for CD34+ HSPC collection for the development and validation of a mutation-specific BE system.
During the treatment phase, participants will receive a one-time infusion of the BE autologous HSPC (study product) after the administration of Campath (alemtuzumab) and of busulfan conditioning (total 12 mg/kg with a targeted total AUC of 65,000 ng/mL x hr). Sirolimus will be initiated on Day -1 and may be given for approximately 3-6 months.
Participants will have follow-up evaluations at months 3, 6, 12, 18, and 24, and yearly thereafter until 5 years after treatment. Key study assessments include adverse event (AE) assessment, blood laboratory evaluations of functional protein made from the target gene (CYBB, encodes for gp91^phox), and deoxyribonucleic acid (DNA) sequencing to identify rates of gene repair and off-target mutation.
The final study follow-up under this protocol will be at 5 years, but long-term follow-up under a separate NIH protocol will continue annually to 15 years after treatment.
Objectives:
Primary Objectives:
- To evaluate the safety of BE autologous CD34+ cells.
- To evaluate the efficacy of BE autologous CD34+ cells.
Secondary Objectives:
-To evaluate:
- Efficiency of base editing (percentages of target nucleotide conversion).
- Engraftment capability of BE HSPCs.
- Efficiency in restoring gp91^phox expression
- Efficiency in restoring NADPH oxidase function.
- Clinical efficacy.
- Stability of gene correction.
Exploratory Objectives:
-To evaluate:
- Specificity of base editing by assessing rates of off-target edits at top predicted sites.
- Random off-target edits by whole genome sequencing (WGS).
Endpoints:
Primary Endpoints:
- Safety of gene therapy using BE autologous HSPCs as measured by study product-related AEs and serious AEs (SAEs) through 2 years after treatment.
- Efficacy of gene therapy determined as percentages of subjects who have >= 10% oxidase-positive granulocytes at 12 months after infusion.
Secondary Endpoints:
- Determine frequency of converted target nucleotide alleles.
- Assess the frequency of gene-modified alleles compared to infusion product in peripheral blood at 12 months.
- Evaluate efficacy of restoring gp91^phox expression.
- Evaluate efficacy of NADPH oxidase functional restoration as measured by the dihydrorhodamine (DHR) flow cytometry oxidase assay at 12 months after treatment (>=10% oxidase-positive neutrophils), or by quantitative measurement of reactive oxygen species (ROS) using the ferricytochrome C assay on peripheral blood granulocytes.
- Evaluate clinical benefit by improvement of baseline clinical problems such as recurrent infections, growth failure, malnutrition, inflammatory bowel disease, or antibiotic usage.
- Assess stability of gene correction by serial measurement of percent of nucleotide-converted alleles.
Exploratory Endpoints:
- Evaluate specificity by assessing for off-target edits at predicted sites with high-throughput sequencing of the 5 most common candidate off-target loci identified by a comprehensive in vitro screen, Circularization for High-throughput Analysis of Nuclease Genome-wide Effects by sequencing (CHANGE-seq-BE), in peripheral blood cells.
- Determine rate of random off-target edits WGS.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single Arm Study | Experimental | Drug: Campath, Drug: Sirolimus, Biological: Base-edited hematopoietic stem and progenitor cells, Drug: Busulfan, Drug: Palifermin, Drug: Filgrastim, Drug: Plerixafor |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- ->= 18 years of age.
- Confirmed CYBB c.676 C>T mutation.
- Male patients.
- Clinically stable and eligible to undergo apheresis and conditioning chemotherapy.
- ->=5 x 10^6 cryopreserved cells/kg body weight available for study product manufacturing.
Key exclusion criteria (25 listed)
- Individuals meeting any of the following criteria will be excluded from study participation:
- Untreated, acute infection.
- Elevated anti-gp91 specific autoantibodies >2 x ULN
- Elevated anti-gp91 specific T cells (>10 fold)
- Anti-platelet antibody screening with >1 anti-platelet antibody positive in the presence of an ongoing brain infection; OR >1 anti-platelet antibody positive and considered unsafe for study participation after consultation with hematology specialist.
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 |
|---|---|---|
| CampathImmunomodulating agent: Daily subcutaneous administration beginning Day -9 for 5 days to reduce the risk of an immune response to the protein expressed by the BE HSPCs. | Drug | Single Arm Study |
| SirolimusImmunomodulating agent: Daily oral dosing beginning Day -1 for approximately 3 to 6 months to reduce the risk of an immune response to the protein expressed by the BE HSPCs. | Drug | Single Arm Study |
| Base-edited hematopoietic stem and progenitor cellsInvestigational/Study Agent: Base-edited autologous CD34 plus hematopoietic stem and progenitor cell product. The product is administered intravenously as a single infusion. This product is under an IND. | Biological | Single Arm Study |
| BusulfanTransplant Conditioning Agent: An alkylating chemotherapy drug to enhance engraftment of the study agent (base-edited stem cells). Conditioning will be given intravenously over 3 days with an approximate total dose of 12mg/kg. Drug levels obtained will be obtained to achieve the targeted total busulfan AUC of 65,000 ng/mL x hr. | Drug | Single Arm Study |
| PaliferminMucositis Prophylaxis Agent: Intravenous infusion of keratinocyte growth factor (Palifermin) at 60 mcg/kg/day before (Days -7 to Day -5 administration of busulfan and (Days 1 to 3) post-busulfan administration to prevent oral mucositis. | Drug | Single Arm Study |
| FilgrastimStem Cell Mobilizing Agent: Subcutaneous administration for 6 consecutive days. It is necessary to mobilize stem cells for collection. | Drug | Single Arm Study |
| PlerixaforStem Cell Mobilizing Agent: Subcutaneous administration for 2 consecutive days to improve stem cell collection. | Drug | Single Arm Study |
Primary outcome
To evaluate the safety of base-edited autologous CD34+ cells
Time frame: Initiated from the time of the infusion of base-edited cells through 2 years post-infusion
Safety of gene therapy using base-edited autologous hematopoietic stem and progenitor cells as measured by study agent related adverse events and serious adverse events
To evaluate the efficacy of base-edited autologous CD34+ cells
Time frame: Assessed 12 months post-infusion of base-edited cells
Efficacy of gene therapy as determined by percentages ofparticipants who have >= 10 percent oxidase-positive granulocytes
6 secondary outcomes
Evaluate the efficiency of base-editing.
Time frame: Assessed 12-24 months post-infusion of base-edited cells
Evaluate the engraftment capability of base-edited hematopoietic stem progenitor cells.
Time frame: Assessed 12-24 months post-infusion of base-edited cells
Evaluate the efficiency in restoring gp91phox expression.
Time frame: Assessed 12-24 months post-infusion of base-edited cells
Evaluate efficacy in restoring NADPH oxidase function.
Time frame: Assessed 12-24 months post-infusion of base-edited cells
Evaluate clinical efficacy
Time frame: Assessed through study completion
Evaluate the stability of gene correction
Time frame: Assessed through study completion
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 5 Nov 2026.
- Background: PubMed 28957631Komor AC, Badran AH, Liu DR. Editing the Genome Without Double-Stranded DNA Breaks. ACS Chem Biol. 2018 Feb 16;13(2):383-388. doi: 10.1021/acschembio.7b00710. Epub 2017 Oct 9.
- Background: PubMed 21190454Kuhns DB, Alvord WG, Heller T, Feld JJ, Pike KM, Marciano BE, Uzel G, DeRavin SS, Priel DA, Soule BP, Zarember KA, Malech HL, Holland SM, Gallin JI. Residual NADPH oxidase and survival in chronic granulomatous disease. N Engl J Med. 2010 Dec 30;363(27):2600-10. doi: 10.1056/NEJMoa1007097.
- Derived from this study: PubMed 39413163Bzhilyanskaya V, Ma L, Liu S, Fox LR, Whittaker MN, Meis RJ, Choi U, Lawson A, Ma M, Theobald N, Burkett S, Sweeney CL, Lazzarotto CR, Tsai SQ, Lack JB, Wu X, Dahl GA, Malech HL, Kleinstiver BP, De Ravin SS. High-fidelity PAMless base editing of hematopoietic stem cells to treat chronic granulomatous disease. Sci Transl Med. 2024 Oct 16;16(769):eadj6779. doi: 10.1126/scitranslmed.adj6779. Epub 2024 Oct 16.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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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.
Suk S De Ravin, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
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 Campath, Sirolimus and Base-edited hematopoietic stem and progenitor cells in people with Chronic Granulomatous Disease (CGD) and X-Linked Chronic Granulomatous Disease, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
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 12 inclusion and 25 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 5 Nov 2026. 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 States. 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 Suk S De Ravin, M.D. ((301) 496-6772, sderavin@mail.nih.gov), 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 base-edited autologous CD34+ cells (time frame: Initiated from the time of the infusion of base-edited cells through 2 years post-infusion). 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?
On the ClinicalTrials.gov record for NCT06325709, which also lists 3 linked publications.
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 5 Nov 2026.