Wiskott-Aldrich SyndromePhase 3NCT03837483
A Clinical Study to Evaluate the Use of a Cryopreserved Formulation of OTL-103 in Subjects With Wiskott-Aldrich Syndrome
A Phase 3 study testing OTL-103 in people with Wiskott-Aldrich Syndrome, run by Fondazione Telethon at 2 sites in 2 countries.
Trial summary
This is an open-label, single arm study to evaluate the cryopreserved formulation of OTL-103 Gene Therapy. OTL-103 consists of autologous CD34+ hematopoietic stem cells in which the gene encoding for the Wiskott-Aldrich Syndrome is introduced by means of a third generation lentiviral vector. Read more about this study
- Who is it for?
- Ages Up to 65 years
- Conditions the study is for
- Wiskott-Aldrich Syndrome
- What is being tested?
- OTL-103
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 21 Jan 2019to Sep 2027
- Phase
- Phase 3
- 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 Up to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age: up to 65 years
- Diagnosis of WAS defined by genetic mutation and at least one of the following criteria:
- Severe Wiskott-Aldrich Syndrome (WAS) gene mutation, defined by literature data (genotype/phenotype studies).;
- Absent WASP expression, assessed by flow cytometry;
- Severe clinical score (Zhu clinical score ≥ 3);
- No human leukocyte antigen (HLA)-identical related donor available for hematopoietic stem cells transplant (HSCT).
Who cannot join
- End-organ dysfunction, severe active infection not responsive to treatment or other severe disease or clinical condition which, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
- Malignant neoplasia (except local skin cancer) or a documented history of hereditary cancer syndrome.
- Myelodysplasia, cytogenetic alterations characteristic of myelodysplastic syndrome and acute myeloid leukaemia , or other serious haematological disorders
- Documented human immunodeficiency virus (HIV) infection
- Prior allogeneic hematopoietic stem cell transplantation, with evidence of residual cells of donor origin
- Symptomatic herpes zoster, not responsive to specific treatment
Show all 11Show fewer
- Evidence of acute tuberculosis
- Acute or chronic stable Hepatitis B
- Presence of positive Hepatitis C RNA test result at screening
- Patients not eligible for mobilization protocols in order to obtain CD34+ cells
- Previous Gene Therapy
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site
Children's Healthcare of Atlanta, Inc
Atlanta, Georgia, 30329
Italy1 site
Ospedale San Raffaele - Telethon Institute for Gene Therapy (OSR-TIGET)
Milan, 20132
About this study
Official title: A Single Arm, Open-label Clinical Trial of Hematopoietic Stem Cell Gene Therapy With Cryopreserved Autologous CD34+ Cells Transduced With Lentiviral Vector Encoding WAS cDNA in Subjects With Wiskott-Aldrich Syndrome (WAS)
This is an open-label, single arm study to evaluate the cryopreserved formulation of OTL-103 Gene Therapy. OTL-103 consists of autologous CD34+ hematopoietic stem cells in which the gene encoding for the Wiskott-Aldrich Syndrome is introduced by means of a third generation lentiviral vector.
- Conditions
- Wiskott-Aldrich Syndrome
- Being tested
- OTL-103
- Medical subject headings
- Wiskott-Aldrich Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OTL-103Genetic
Autologous hematopoietic stem cells collected from mobilized peripheral blood transduced ex vivo with a lentiviral vector encoding the WAS cDNA
| Study group | Role | What they receive |
|---|---|---|
| Gene Therapy | Experimental | OTL-103, Autologous CD34+ hematopoietic stem cells transduced ex vivo with a lentiviral vector encoding the human WAS gene Receives: Genetic: OTL-103 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Annualized rate of severe infections from 6 to 18 months after gene therapy compared with 1 year before gene therapy
Measured: 18 months
Annualized rate of moderate and severe bleeding episodes up to 1 year after gene therapy compared with 1 year before gene therapy
Measured: 12 months
Secondary outcomes (6)
Evaluation of the overall survival
Measured: 36 months
Number of patients with Vector copy number (VCN)/cell > 0.1 measured in peripheral blood-derived CD3+ cells
Measured: 2 years
Percentage of WAS protein expression increased from pre-treatment levels in lymphocytes
Measured: 2 years
Percentage of WAS protein expression increased from pre-treatment levels in platelets
Measured: 2 years
Number of participants with successful engraftment of OTL-103
Engraftment of of OTL-103 is measured by hematological reconstitution of an absolute neutrophil count > 500 cell/ul
Measured: 6 months
The number of subjects presenting with malignancies or abnormal clonal proliferation
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2019
- Study start21 Jan 2019
- Primary completion18 Mar 2024
- Study completionSep 2027 (estimated)
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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fondazione Telethon
- Sponsor type
- University, hospital or other
- Collaborators
- Ospedale San Raffaele
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03837483
- Sponsor's protocol ID
- OTL-103-4
- Other IDs
- 2018-003842-18, 2018
- Status last verified
- Sep 2025
- First submitted
- 8 Feb 2019
- Last updated
- 29 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ferrua F, Cenciarelli S, Giannelli S, Galimberti S, Chandrakasan S, Fraschetta F, Caputo C, Sala D, Monti I, Barzaghi F, Calbi V, Canarutto D, Consiglieri G, Doglio M, Fumagalli F, Gallo V, Migliavacca M, Recupero S, Tucci F, Orsini A, Milani R, Datukishvili M, De Gregori S, Montini E, Silvani P, Soncini M, Tomasetto E, van Rossem K, Castagnaro L, Miotto F, Zancan S, Scotti C, Russell S, Naldini L, Ciceri F, Bernardo ME, Parikh S, Cicalese MP, Aiuti A; WAS Gene Therapy Group. Etuvetidigene Autotemcel for the Treatment of Wiskott-Aldrich Syndrome. N Engl J Med. 2026 Sep 24;395(12):1193-1205. doi: 10.1056/NEJMoa2515005.
PubMed 42777242Quaranta P, Basso-Ricci L, Jofra Hernandez R, Pacini G, Naldini MM, Barcella M, Seffin L, Pais G, Spinozzi G, Benedicenti F, Pietrasanta C, Cheong JG, Ronchi A, Pugni L, Dionisio F, Monti I, Giannelli S, Darin S, Fraschetta F, Barera G, Ferrua F, Calbi V, Ometti M, Di Micco R, Mosca F, Josefowicz SZ, Montini E, Calabria A, Bernardo ME, Cicalese MP, Gentner B, Merelli I, Aiuti A, Scala S. Circulating hematopoietic stem/progenitor cell subsets contribute to human hematopoietic homeostasis. Blood. 2024 May 9;143(19):1937-1952. doi: 10.1182/blood.2023022666.
PubMed 38446574
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Arm, Open-label Clinical Trial of Hematopoietic Stem Cell Gene Therapy With Cryopreserved Autologous CD34+ Cells Transduced With Lentiviral Vector Encoding WAS cDNA in Subjects With Wiskott-Aldrich Syndrome (WAS)
- ClinicalTrials.gov ID
- NCT03837483
- Acronym / sponsor ID
- OTL-103-4
- Conditions
- Wiskott-Aldrich Syndrome
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Fondazione TelethonUniversity, hospital or other
- Collaborators
- Ospedale San Raffaele
- Study start
- 21 Jan 2019 (actual)
- Primary completion
- 18 Mar 2024 (actual)
- Study completion
- Sep 2027 (estimated)
- First posted
- 12 Feb 2019 (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.
This is an open-label, single arm study to evaluate the cryopreserved formulation of OTL-103 Gene Therapy. OTL-103 consists of autologous CD34+ hematopoietic stem cells in which the gene encoding for the Wiskott-Aldrich Syndrome is introduced by means of a third generation lentiviral vector.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Gene Therapy | Experimental | Genetic: OTL-103OTL-103, Autologous CD34+ hematopoietic stem cells transduced ex vivo with a lentiviral vector encoding the human WAS gene |
Who may qualify
- Ages
- Up to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Age: up to 65 years
- Diagnosis of WAS defined by genetic mutation and at least one of the following criteria:
- No human leukocyte antigen (HLA)-identical related donor available for hematopoietic stem cells transplant (HSCT).
Key exclusion criteria (11 listed)
- End-organ dysfunction, severe active infection not responsive to treatment or other severe disease or clinical condition which, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
- Malignant neoplasia (except local skin cancer) or a documented history of hereditary cancer syndrome.
- Myelodysplasia, cytogenetic alterations characteristic of myelodysplastic syndrome and acute myeloid leukaemia , or other serious haematological disorders
- Documented human immunodeficiency virus (HIV) infection
- Prior allogeneic hematopoietic stem cell transplantation, with evidence of residual cells of donor origin
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 |
|---|---|---|
| OTL-103Autologous hematopoietic stem cells collected from mobilized peripheral blood transduced ex vivo with a lentiviral vector encoding the WAS cDNA | Genetic | Gene Therapy |
Primary outcome
Annualized rate of severe infections from 6 to 18 months after gene therapy compared with 1 year before gene therapy
Time frame: 18 months
Annualized rate of moderate and severe bleeding episodes up to 1 year after gene therapy compared with 1 year before gene therapy
Time frame: 12 months
6 secondary outcomes
Evaluation of the overall survival
Time frame: 36 months
Number of patients with Vector copy number (VCN)/cell > 0.1 measured in peripheral blood-derived CD3+ cells
Time frame: 2 years
Percentage of WAS protein expression increased from pre-treatment levels in lymphocytes
Time frame: 2 years
Percentage of WAS protein expression increased from pre-treatment levels in platelets
Time frame: 2 years
Number of participants with successful engraftment of OTL-103
Time frame: 6 months
The number of subjects presenting with malignancies or abnormal clonal proliferation
Time frame: 2 years
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 29 Sep 2025.
- Derived from this study: PubMed 42777242Ferrua F, Cenciarelli S, Giannelli S, Galimberti S, Chandrakasan S, Fraschetta F, Caputo C, Sala D, Monti I, Barzaghi F, Calbi V, Canarutto D, Consiglieri G, Doglio M, Fumagalli F, Gallo V, Migliavacca M, Recupero S, Tucci F, Orsini A, Milani R, Datukishvili M, De Gregori S, Montini E, Silvani P, Soncini M, Tomasetto E, van Rossem K, Castagnaro L, Miotto F, Zancan S, Scotti C, Russell S, Naldini L, Ciceri F, Bernardo ME, Parikh S, Cicalese MP, Aiuti A; WAS Gene Therapy Group. Etuvetidigene Autotemcel for the Treatment of Wiskott-Aldrich Syndrome. N Engl J Med. 2026 Sep 24;395(12):1193-1205. doi: 10.1056/NEJMoa2515005.
- Derived from this study: PubMed 38446574Quaranta P, Basso-Ricci L, Jofra Hernandez R, Pacini G, Naldini MM, Barcella M, Seffin L, Pais G, Spinozzi G, Benedicenti F, Pietrasanta C, Cheong JG, Ronchi A, Pugni L, Dionisio F, Monti I, Giannelli S, Darin S, Fraschetta F, Barera G, Ferrua F, Calbi V, Ometti M, Di Micco R, Mosca F, Josefowicz SZ, Montini E, Calabria A, Bernardo ME, Cicalese MP, Gentner B, Merelli I, Aiuti A, Scala S. Circulating hematopoietic stem/progenitor cell subsets contribute to human hematopoietic homeostasis. Blood. 2024 May 9;143(19):1937-1952. doi: 10.1182/blood.2023022666.
- Individual participant dataSharing planned: No
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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 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing OTL-103 in people with Wiskott-Aldrich Syndrome, run by Fondazione Telethon at 2 sites in 2 countries.
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 6 inclusion and 11 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: under way, not looking for participants, as of the sponsor's last update on 29 Sep 2025. 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 States, Italy. 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 phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
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?
Annualized rate of severe infections from 6 to 18 months after gene therapy compared with 1 year before gene therapy (time frame: 18 months). 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 NCT03837483, 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 29 Sep 2025.