X-linked Chronic Granulomatous DiseasePhase 1/2NCT01906541
Gene Therapy for X-CGD
A Phase 1/2 study testing ex-vivo gene-therapy in people with X-linked Chronic Granulomatous Disease, run by Hubert Serve, Prof., MD at 1 site in Germany.
Trial summary
X-linked chronic granulomatous disease (X-CGD) is a rare inherited immune defect, which is caused by the inability of phagocytic cells to produce reactive oxygen species due to a defect in the gp91phox subunit of the NADPH oxidase complex. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- X-linked Chronic Granulomatous Disease
- What is being tested?
- ex-vivo gene-therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteGermany
- Study dates
- Jul 2013to Dec 2019
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Verified diagnosis of the X-linked form of chronic granulomatous disease, with loss of gp91phox expression (Western Blot). Evidence of less than 5% of normal oxidase production in circulating neutrophil granulocytes as measured by dihydrorhodamine- (DHR-) and nitro blue tetrazolium- (NBT-) assay
- History of severe chronic infections with life-threatening course or severe steroid- sensitive or steroid insensitive granulomatous disease, with necessity of inpatient treatment, without sustained improvement even under maximum conservative treatment measures
- No Human Leukocyte Antigen (HLA) identical (10/10 match) sibling- or unrelated donor, or contraindications for allogenic stem cell transplantation in presence of a suitable donor. The lack of an HLA-identical (10/10 match) sibling- or unrelated donor has to be confirmed by an unsuccessful search in national and international donor registers for at leat 3 months
- Normal organ-function: glomerular filtration rate (GFR) ≥ 60ml/min., Bilirubin ≤ 1.5-fold upper reference-level, normal parameters for liver enzymes and clotting (TPZ 75-100%, partial thromboplastin time (PTT) 30-38sec, Fibrinogen 200-400mg/dl), Leukocytes > 3 x 10^9/l, Granulocytes > 1.5 x 10^9/l, Thrombocytes >100 x 10^9/l
- Contraception from start of G-CSF application until 1 year after retransfusion of the gene-corrected cells
- No interferon-gamma injection within two weeks prior to hematopoietic stem cell mobilization
- Karnofsky-Index > 70%
- Signed informed consent
Who cannot join
- Patients with non-controlled acute infections
- Severe cardiac or pulmonary malfunctions: ejection fraction < 60%, valvular heart disease > II°, arrhythmia requiring therapy, forced expiratory volume at one second/vital capacity (FEV1/VC) < 75% , diffusion capacity of lung for carbon monoxide (DLCO) <60%
- Bilirubin > 1.5-fold upper reference-level
- HIV-, Hepatitis B- or C - infection
- Contraindications for G-CSF administration, as autoimmune vasculitis.
- Contraindications for stem cell apheresis, as low hemoglobin < 8g/dl, cardiovascular instability or severe coagulopathy
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- Pregnancy or breast-feeding
- Drug- or alcohol-abuse
- Lack of search for an unrelated donor
- Patients with a HLA 9/10 mismatched unrelated donor (MMUD) will be excluded, if a thorough risk-benefit analysis favors allogenic hematopoietic stem cell transplantation (HSCT)
Trial locations and contacts
1 site in 1 country.
Germany1 site, 1 recruiting
- Recruiting
University Hospital Frankfurt
Frankfurt am Main, 60595
Joachim Schwäble, MD, 0049/69 /67824900, schwaeble@em.uni-frankfurt.de
About this study
Official title: A Phase I/II Gene Therapy Trial for X-CGD With a SIN Gammaretroviral Vector
X-linked chronic granulomatous disease (X-CGD) is a rare inherited immune defect, which is caused by the inability of phagocytic cells to produce reactive oxygen species due to a defect in the gp91phox subunit of the NADPH oxidase complex. X-CGD patients suffer from recurrent and life-threatening infections and severe hyperinflammatory complications.
The only curative treatment for X-CGD is allogenic hematopoietic stem cell transplantation, but this procedure implies severe risks and many patients lack an appropriate donor. Therefore alternative curative approaches are urgently needed. In this study, patients will be treated with gene-corrected autologous CD34+ cells, using a SIN gammaretroviral vector for ex-vivo gene-therapy.
- Conditions
- X-linked Chronic Granulomatous Disease
- Being tested
- ex-vivo gene-therapy
- Keywords
- X-CGD, chronic granulomatous disease, gene-therapy
- Medical subject headings
- Granulomatous Disease, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ex-vivo gene-therapyGenetic
transplantation autologous CD34+ cells, transduced with a SIN gammaretroviral vector
| Study group | Role | What they receive |
|---|---|---|
| ex-vivo gene-therapy | Experimental | transplantation of genetically modified autologous CD34+ cells Receives: Genetic: ex-vivo gene-therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Transduction rate of granulocyte colony-stimulating factor (G-CSF) mobilized peripheral CD34+ cells from CGD patients with a SIN gamma retroviral vector
Measured: 1 week
Engraftment rate of the transduced CD34+ cells in the patients
Measured: 5 years
Long-term expression of the transgene (rate of gp91phox positive cells) in circulating cells in the peripheral blood
Measured: 5 years
Functional reconstitution of the NADPH oxidase in circulating cells of the peripheral blood (% DHR positive cells)
Measured: 5 years
Frequency and severity of unexpected toxic adverse events during and after infusion of the genetically modified CD34+ cells
Measured: 5 years
Secondary outcomes (4)
Frequency of infections as indicator for the clinical benefit for the patients
Measured: 5 years
Proliferation rate of CD34+ cells in ex-vivo culture under serum-free conditions
Measured: up to 3 weeks
Differentiation rate of CD34+ cells (as measured by flow cytometry) in ex-vivo culture under serum-free conditions
Measured: up to 3 weeks
Transduction rate of CD34+ cells in ex-vivo culture under serum-free conditions
Measured: up to 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2013 (estimated)
- Study startJul 2013
- Primary completionDec 2013 (estimated)
- Study completionDec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for X-linked Chronic Granulomatous DiseaseStudies 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
- Hubert Serve, Prof., MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Hubert Serve, Prof., MD, Johann Wolfgang Goethe University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01906541
- Sponsor's protocol ID
- X-CGD
- Status last verified
- Aug 2013
- First submitted
- 15 Jul 2013
- Last updated
- 2 Aug 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Gene Therapy Trial for X-CGD With a SIN Gammaretroviral Vector
- ClinicalTrials.gov ID
- NCT01906541
- Acronym / sponsor ID
- X-CGD
- Conditions
- X-linked Chronic Granulomatous Disease
- Keywords
- X-CGD, chronic granulomatous disease, gene-therapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 5 participants (estimated)
- Lead sponsor
- Hubert Serve, Prof., MDUniversity, hospital or other
- Study start
- Jul 2013
- Primary completion
- Dec 2013 (estimated)
- Study completion
- Dec 2019 (estimated)
- First posted
- 24 Jul 2013 (estimated)
- 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.
X-linked chronic granulomatous disease (X-CGD) is a rare inherited immune defect, which is caused by the inability of phagocytic cells to produce reactive oxygen species due to a defect in the gp91phox subunit of the NADPH oxidase complex. X-CGD patients suffer from recurrent and life-threatening infections and severe hyperinflammatory complications.
The only curative treatment for X-CGD is allogenic hematopoietic stem cell transplantation, but this procedure implies severe risks and many patients lack an appropriate donor. Therefore alternative curative approaches are urgently needed. In this study, patients will be treated with gene-corrected autologous CD34+ cells, using a SIN gammaretroviral vector for ex-vivo gene-therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ex-vivo gene-therapy | Experimental | Genetic: ex-vivo gene-therapytransplantation of genetically modified autologous CD34+ cells |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Verified diagnosis of the X-linked form of chronic granulomatous disease, with loss of gp91phox expression (Western Blot). Evidence of less than 5% of normal oxidase production in circulating neutrophil granulocytes as measured by dihydrorhodamine- (DHR-) and nitro blue tetrazolium- (NBT-) assay
- History of severe chronic infections with life-threatening course or severe steroid- sensitive or steroid insensitive granulomatous disease, with necessity of inpatient treatment, without sustained improvement even under maximum conservative treatment measures
- No Human Leukocyte Antigen (HLA) identical (10/10 match) sibling- or unrelated donor, or contraindications for allogenic stem cell transplantation in presence of a suitable donor. The lack of an HLA-identical (10/10 match) sibling- or unrelated donor has to be confirmed by an unsuccessful search in national and international donor registers for at leat 3 months
- Normal organ-function: glomerular filtration rate (GFR) ≥ 60ml/min., Bilirubin ≤ 1.5-fold upper reference-level, normal parameters for liver enzymes and clotting (TPZ 75-100%, partial thromboplastin time (PTT) 30-38sec, Fibrinogen 200-400mg/dl), Leukocytes > 3 x 10^9/l, Granulocytes > 1.5 x 10^9/l, Thrombocytes >100 x 10^9/l
- Contraception from start of G-CSF application until 1 year after retransfusion of the gene-corrected cells
Key exclusion criteria (10 listed)
- Patients with non-controlled acute infections
- Severe cardiac or pulmonary malfunctions: ejection fraction < 60%, valvular heart disease > II°, arrhythmia requiring therapy, forced expiratory volume at one second/vital capacity (FEV1/VC) < 75% , diffusion capacity of lung for carbon monoxide (DLCO) <60%
- Bilirubin > 1.5-fold upper reference-level
- HIV-, Hepatitis B- or C - infection
- Contraindications for G-CSF administration, as autoimmune vasculitis.
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 |
|---|---|---|
| ex-vivo gene-therapytransplantation autologous CD34+ cells, transduced with a SIN gammaretroviral vector | Genetic | ex-vivo gene-therapy |
Primary outcome
Transduction rate of granulocyte colony-stimulating factor (G-CSF) mobilized peripheral CD34+ cells from CGD patients with a SIN gamma retroviral vector
Time frame: 1 week
Engraftment rate of the transduced CD34+ cells in the patients
Time frame: 5 years
Long-term expression of the transgene (rate of gp91phox positive cells) in circulating cells in the peripheral blood
Time frame: 5 years
Functional reconstitution of the NADPH oxidase in circulating cells of the peripheral blood (% DHR positive cells)
Time frame: 5 years
Frequency and severity of unexpected toxic adverse events during and after infusion of the genetically modified CD34+ cells
Time frame: 5 years
4 secondary outcomes
Frequency of infections as indicator for the clinical benefit for the patients
Time frame: 5 years
Proliferation rate of CD34+ cells in ex-vivo culture under serum-free conditions
Time frame: up to 3 weeks
Differentiation rate of CD34+ cells (as measured by flow cytometry) in ex-vivo culture under serum-free conditions
Time frame: up to 3 weeks
Transduction rate of CD34+ cells in ex-vivo culture under serum-free conditions
Time frame: up to 12 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2013.
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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. This study is not recruiting at the moment.
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 ex-vivo gene-therapy in people with X-linked Chronic Granulomatous Disease, run by Hubert Serve, Prof., MD at 1 site in Germany.
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 8 inclusion and 10 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: status not confirmed, as of the sponsor's last update on 2 Aug 2013. 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 Germany. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Hubert Serve, Prof., MD (0049/69/6301 ext. 4634, serve@em.uni-frankfurt.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Transduction rate of granulocyte colony-stimulating factor (G-CSF) mobilized peripheral CD34+ cells from CGD patients with a SIN gamma retroviral vector (time frame: 1 week). The study lists 5 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 2 Aug 2013.