Wiskott-Aldrich SyndromePhase 1/2NCT01347242
Gene Therapy for Wiskott-Aldrich Syndrome (WAS)
A Phase 1/2 study testing Autologous CD34 positive cells transduced with a lentiviral vector containing human WAS gene in people with Wiskott-Aldrich Syndrome, run by Genethon at 2 sites in United Kingdom.
Trial summary
This is a phase I/II study to evaluate the safety and efficacy of Hematopoietic Stem Cell genetherapy for the Wiskott-Aldrich Syndrome. Read more about this study
- Who is it for?
- Any age, men only
- Conditions the study is for
- Wiskott-Aldrich Syndrome
- What is being tested?
- Autologous CD34 positive cells transduced with a lentiviral vector containing human WAS gene
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- Mar 2011to 13 Nov 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 Any age
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- males of all ages
- severe WAS (clinical score 3-5) or absence of WAS protein in peripheral blood mononuclear cells determined by Western blotting and flow cytometry
- molecular confirmation by WAS gene DNA sequencing
- lack of HLA-genotypically identical bone marrow or of a 10/10 antigen HLA-matched unrelated donor or cord blood after 3 month search
- parental, guardian, patient signed informed consent/assent
- willing to return for follow-up
Show all 9Show fewer
- only for patients who have received previous allogenic hematopoietic stem cell transplant:
- failed allogenic hematopoietic stem cell transplant
- contraindication to repeat transplantation
Who cannot join
- patient with HLA-genotypically identical bone marrow
- patient with 10/10 antigen HLA-matched unrelated donor or cord blood
- contraindication to leukapheresis
- contraindication to bone marrow harvest
- contraindication to administration of conditioning medication
- HIV positive patient
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites
Great Ormond Street Hospital
London, WC1N 1EH
Royal Free Hospital
London, WC1N 1EH
About this study
Official title: Phase I/II Clinical Trial of Haematopoietic Stem Cell Gene Therapy for the Wiskott-Aldrich Syndrome
This is a phase I/II study to evaluate the safety and efficacy of Hematopoietic Stem Cell genetherapy for the Wiskott-Aldrich Syndrome.
Read the detailed description
This clinical trial is an ex vivo gene therapy trial. The investigational product corresponds to autologous CD34+ cells transduced with a lentiviral vector harboring the human WASP gene.
- Conditions
- Wiskott-Aldrich Syndrome
- Being tested
- Autologous CD34 positive cells transduced with a lentiviral vector containing human WAS gene
- Keywords
- Wiskott-Aldrich Syndrome, Primary immune deficiency, ex vivo gene therapy, hematopoietic stem cells
- Medical subject headings
- Wiskott-Aldrich Syndrome, Primary Immunodeficiency Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous CD34 positive cells transduced with a lentiviral vector containing human WAS geneGenetic
transplantation of patient's autologous CD34+ cells transduced with lentiviral vector containing human WAS gene
| Study group | Role | What they receive |
|---|---|---|
| study treatment | Experimental | autologous CD34 positive cells transduced with a lentiviral vector containing the human WAS gene Receives: Genetic: Autologous CD34 positive cells transduced with a lentiviral vector containing human WAS gene |
What is being measured
The primary outcome is the main question the study is designed to answer.
Improvement in the eczema status
Improvement in the eczema status as compared with the baseline status at study entry on clinical evaluation
Measured: 2 years
Reduction in the frequency and severity of infection episodes
Reduction in the frequency and severity of infection episodes as compared with the baseline status and the patient's historical data collected over the 2 years prior to study entry
Measured: 2 years
Reduction in the frequency and severity of bruising and bleeding episodes
Reduction in the frequency and severity of bruising and bleeding episodes as compared with the baseline status and the patient's historical data collected over the 2 years prior to study entry
Measured: 2 years
Reduction in the frequency and severity of autoimmune disorders
Reduction in the frequency and severity of autoimmune disorders as compared with the baseline status at study entry
Measured: 2 years
Reduction in the number of disease related days of hospitalization
Reduction in the number of disease related days of hospitalization as compared with the patient's historical data collected over the 2 years prior to study entry
Measured: 2 years
Secondary outcomes (7)
Occurrence and type of adverse events
Occurrence and type of adverse events reported during the course of the study
Measured: 2 years
Change in medical conditions
Assessment of weight, vital signs, ECG and laboratory exams during the course of the study
Measured: 2 years
Safety of lentivirus gene transfer into Hematopoietic Stem Cells
Detection of replication competent lentivirus (RCL) and lentivirus integration sites analysis
Measured: 3, 6, 12, 24 months / 6, 12, 18, 24 months
Improvement of microthrombocytopenia
Improvement of microthrombocytopenia as compared with the baseline evaluation at study entry
Measured: 3, 6, 12, 24 months
Decrease in the number and volume of platelets transfusions
Decrease in the number and volume of platelets transfusions as compared with patient's historical data collected over the 2 years prior to study entry
Measured: 2 years
Evidence of sustained engrafment of WASP-expressing transduced cells
Quantification of vector copy numbers and detection of vector-derived WASP expression
Measured: 6 weeks, 1, 3, 6, 9, 12, 18 & 24 months
Reconstitution of humoral and cell mediated immunity
Reconstitution of humoral and cell mediated immunity as compared with the baseline evaluation at study entry
Measured: 9, 12, 18 & 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2011 (estimated)
- Study startMar 2011
- Primary completion13 Nov 2019
- Study completion13 Nov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Wiskott-Aldrich SyndromeStudies 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
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genethon
- Sponsor type
- University, hospital or other
- Collaborators
- Great Ormond Street Hospital for Children NHS Foundation Trust, Institute of Child Health
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01347242
- Sponsor's protocol ID
- GTG002.07
- Status last verified
- Nov 2019
- First submitted
- 3 May 2011
- Last updated
- 3 Jun 2021
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Magnani A, Semeraro M, Adam F, Booth C, Dupre L, Morris EC, Gabrion A, Roudaut C, Borgel D, Toubert A, Clave E, Abdo C, Gorochov G, Petermann R, Guiot M, Miyara M, Moshous D, Magrin E, Denis A, Suarez F, Lagresle C, Roche AM, Everett J, Trinquand A, Guisset M, Bayford JX, Hacein-Bey-Abina S, Kauskot A, Elfeky R, Rivat C, Abbas S, Gaspar HB, Macintyre E, Picard C, Bushman FD, Galy A, Fischer A, Six E, Thrasher AJ, Cavazzana M. Long-term safety and efficacy of lentiviral hematopoietic stem/progenitor cell gene therapy for Wiskott-Aldrich syndrome. Nat Med. 2022 Jan;28(1):71-80. doi: 10.1038/s41591-021-01641-x. Epub 2022 Jan 24.
PubMed 35075289Morris EC, Fox T, Chakraverty R, Tendeiro R, Snell K, Rivat C, Grace S, Gilmour K, Workman S, Buckland K, Butler K, Chee R, Salama AD, Ibrahim H, Hara H, Duret C, Mavilio F, Male F, Bushman FD, Galy A, Burns SO, Gaspar HB, Thrasher AJ. Gene therapy for Wiskott-Aldrich syndrome in a severely affected adult. Blood. 2017 Sep 14;130(11):1327-1335. doi: 10.1182/blood-2017-04-777136. Epub 2017 Jul 17.
PubMed 28716862
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Clinical Trial of Haematopoietic Stem Cell Gene Therapy for the Wiskott-Aldrich Syndrome
- ClinicalTrials.gov ID
- NCT01347242
- Acronym / sponsor ID
- GTG002.07
- Conditions
- Wiskott-Aldrich Syndrome
- Keywords
- Wiskott-Aldrich Syndrome, Primary immune deficiency, ex vivo gene therapy, hematopoietic stem cells
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- GenethonUniversity, hospital or other
- Collaborators
- Great Ormond Street Hospital for Children NHS Foundation Trust, Institute of Child Health
- Study start
- Mar 2011 (actual)
- Primary completion
- 13 Nov 2019 (actual)
- Study completion
- 13 Nov 2019 (actual)
- First posted
- 4 May 2011 (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.
This is a phase I/II study to evaluate the safety and efficacy of Hematopoietic Stem Cell genetherapy for the Wiskott-Aldrich Syndrome.
Detailed description
This clinical trial is an ex vivo gene therapy trial. The investigational product corresponds to autologous CD34+ cells transduced with a lentiviral vector harboring the human WASP gene.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| study treatment | Experimental | Genetic: Autologous CD34 positive cells transduced with a lentiviral vector containing human WAS geneautologous CD34 positive cells transduced with a lentiviral vector containing the human WAS gene |
Who may qualify
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- males of all ages
- severe WAS (clinical score 3-5) or absence of WAS protein in peripheral blood mononuclear cells determined by Western blotting and flow cytometry
- molecular confirmation by WAS gene DNA sequencing
- lack of HLA-genotypically identical bone marrow or of a 10/10 antigen HLA-matched unrelated donor or cord blood after 3 month search
- parental, guardian, patient signed informed consent/assent
Key exclusion criteria (6 listed)
- patient with HLA-genotypically identical bone marrow
- patient with 10/10 antigen HLA-matched unrelated donor or cord blood
- contraindication to leukapheresis
- contraindication to bone marrow harvest
- contraindication to administration of conditioning medication
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 |
|---|---|---|
| Autologous CD34 positive cells transduced with a lentiviral vector containing human WAS genetransplantation of patient's autologous CD34+ cells transduced with lentiviral vector containing human WAS gene | Genetic | study treatment |
Primary outcome
Improvement in the eczema status
Time frame: 2 years
Improvement in the eczema status as compared with the baseline status at study entry on clinical evaluation
Reduction in the frequency and severity of infection episodes
Time frame: 2 years
Reduction in the frequency and severity of infection episodes as compared with the baseline status and the patient's historical data collected over the 2 years prior to study entry
Reduction in the frequency and severity of bruising and bleeding episodes
Time frame: 2 years
Reduction in the frequency and severity of bruising and bleeding episodes as compared with the baseline status and the patient's historical data collected over the 2 years prior to study entry
Reduction in the frequency and severity of autoimmune disorders
Time frame: 2 years
Reduction in the frequency and severity of autoimmune disorders as compared with the baseline status at study entry
Reduction in the number of disease related days of hospitalization
Time frame: 2 years
Reduction in the number of disease related days of hospitalization as compared with the patient's historical data collected over the 2 years prior to study entry
7 secondary outcomes
Occurrence and type of adverse events
Time frame: 2 years
Change in medical conditions
Time frame: 2 years
Safety of lentivirus gene transfer into Hematopoietic Stem Cells
Time frame: 3, 6, 12, 24 months / 6, 12, 18, 24 months
Improvement of microthrombocytopenia
Time frame: 3, 6, 12, 24 months
Decrease in the number and volume of platelets transfusions
Time frame: 2 years
Evidence of sustained engrafment of WASP-expressing transduced cells
Time frame: 6 weeks, 1, 3, 6, 9, 12, 18 & 24 months
Reconstitution of humoral and cell mediated immunity
Time frame: 9, 12, 18 & 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2021.
- Derived from this study: PubMed 35075289Magnani A, Semeraro M, Adam F, Booth C, Dupre L, Morris EC, Gabrion A, Roudaut C, Borgel D, Toubert A, Clave E, Abdo C, Gorochov G, Petermann R, Guiot M, Miyara M, Moshous D, Magrin E, Denis A, Suarez F, Lagresle C, Roche AM, Everett J, Trinquand A, Guisset M, Bayford JX, Hacein-Bey-Abina S, Kauskot A, Elfeky R, Rivat C, Abbas S, Gaspar HB, Macintyre E, Picard C, Bushman FD, Galy A, Fischer A, Six E, Thrasher AJ, Cavazzana M. Long-term safety and efficacy of lentiviral hematopoietic stem/progenitor cell gene therapy for Wiskott-Aldrich syndrome. Nat Med. 2022 Jan;28(1):71-80. doi: 10.1038/s41591-021-01641-x. Epub 2022 Jan 24.
- Derived from this study: PubMed 28716862Morris EC, Fox T, Chakraverty R, Tendeiro R, Snell K, Rivat C, Grace S, Gilmour K, Workman S, Buckland K, Butler K, Chee R, Salama AD, Ibrahim H, Hara H, Duret C, Mavilio F, Male F, Bushman FD, Galy A, Burns SO, Gaspar HB, Thrasher AJ. Gene therapy for Wiskott-Aldrich syndrome in a severely affected adult. Blood. 2017 Sep 14;130(11):1327-1335. doi: 10.1182/blood-2017-04-777136. Epub 2017 Jul 17.
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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.
The record lists no contact. Use the official record to reach the sponsor.
2 sites 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 Autologous CD34 positive cells transduced with a lentiviral vector containing human WAS gene in people with Wiskott-Aldrich Syndrome, run by Genethon at 2 sites 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 9 inclusion and 6 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: finished, as of the sponsor's last update on 3 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Improvement in the eczema status (time frame: 2 years). 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?
On the ClinicalTrials.gov record for NCT01347242, which also lists 2 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 3 Jun 2021.