Wiskott-Aldrich Syndrome (WAS)Phase 1/2TIGET-WASNCT01515462

Gene Therapy for Wiskott-Aldrich Syndrome

A Phase 1/2 study testing TLT003 in people with Wiskott-Aldrich Syndrome (WAS), run by Fondazione Telethon at 1 site in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

This is phase I/II protocol to evaluate the safety and efficacy of WAS gene transfer into hematopoietic stem/progenitor cells for the treatment of Wiskott Aldrich Syndrome. Read more about this study

Who is it for?: Any age
Conditions the study is for: Wiskott-Aldrich Syndrome (WAS)
What is being tested?: TLT003
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 8 participants
Where: 1 siteItaly
Study dates: 20 Apr 2010to 4 Oct 2023
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

Diagnosis of WAS defined by genetic mutation and at least one of the following criteria:
Severe WAS mutation
Absence of WASP expression
Severe clinical score (Zhu clinical score ≥ 3
No HLA-identical sibling donor
Negative search for a matched unrelated donor (10/10) or an adequate unrelated cord blood donor (5-6/6) within 4-6 months
Patients of > 5 years of age who are not candidate to unrelated allogeneic transplant based on clinical conditions.
Parental/guardian/patient signed informed consent.

Who cannot join

Patients positive for HIV-infection.
Patients affected by neoplasia.
Patients with cytogenetic alterations typical of MDS/AML.
Patients with end-organ functions or any other severe disease which, in the judgement of the investigator, would make the patient inappropriate for entry into this study.
Patients who underwent an allogeneic haematopoietic stem cell transplantation in the previous 6 months.
Patients who underwent an allogeneic haematopoietic stem cell transplantation with evidence of residual cells of donor origin.

Trial locations and contacts

1 site in 1 country.

Italy1 site

Ospedale San Raffaele - Telethon Institute for Gene Therapy (OSR-TIGET)
Milan, 20132

Other trials in Italy

About this study

Official title: A Phase I/II Clinical Trial of Hematopoietic Stem Cell Gene Therapy for the Wiskott-Aldrich Syndrome

This is phase I/II protocol to evaluate the safety and efficacy of WAS gene transfer into hematopoietic stem/progenitor cells for the treatment of Wiskott Aldrich Syndrome.

Read the detailed description

Wiskott-Aldrich Syndrome (WAS) is an X-linked primary immunodeficiency caused by mutations in the WAS gene which encodes the WAS protein (WASP), a cytoskeletal regulator which is expressed exclusively in hematopoietic cells.

Conditions: Wiskott-Aldrich Syndrome (WAS)
Being tested: TLT003
Keywords: Lentiviral vector, Gene therapy, Wiskott-Aldrich Syndrome, TLT003, Previously GSK2696275, Previously 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.

TLT003Genetic
Also called Previously GSK2696275, Previously OTL-103
TLT003 is an autologous CD34+ cells collected from bone marrow and/or peripheral blood and transduced with a lentiviral vector encoding Wiskott-Aldrich syndrome (WAS) protein

Study groups in NCT01515462
Study group	Role	What they receive
TLT003 gene therapy	Experimental	Eligible subjects will receive intravenous (IV) infusion of TLT003 gene therapy. Subjects affected by WAS who don't have a suitable matched donor for allogenic hematopoietic stem cell transplantation will be included Receives: Genetic: TLT003

What is being measured

The primary outcome is the main question the study is designed to answer.

Safety of Reduced Conditioning Regimen
The absence of prolonged aplasia (defined as ANC <0.5×10^9/L [<500/μL] at Day +60, with no evidence of BM recovery and requiring backup administration) was assumed as demonstrating the safety of the RIC regimen.
Measured: Follow up phase - Median duration: 11.1 years (range: 8.01 -13.3 years)
Safety of Lentivirus Gene Transfer Into HSC
Safety and tolerability of lentiviral-transduced cell infusion. This will be evaluated on the basis of adverse events reporting and monitoring of the systemic reactions to cell infusion.
Measured: after 48 hours after Telethon003 infusion
Sustained Engraftment of Genetically Corrected Haematopoietic Stem Cells in Peripheral Blood and/or in Bone Marrow
Engraftment is characterized by the presence of gene modified cells in the BM or PB compartments. The main indicator of gene correction is detection of the WAS LVV sequences in the HSPCs and their progeny.
The VCN, which is the mean number of integrated copies of the vector sequences per cell genome, was measured using PCR-based methods in DNA samples extracted from BM and PB cell populations at various timepoints post-treatment.
Adequate engraftment was defined as either ≥0.04 VCN/cell in BM CD34+ cells or ≥0.01 VCN/cell in PB CD3+ cells.
Measured: at 1 year after Telethon003 infusion
Presence of Detectable Vector-derived WASP
The percentage of subjects who present the proportion of PB cells expressing WASP was assessed by flow cytometry analysis.
Measured: Median duration: 11.1 years (range: 8.01 -13.3 years)
Improved T-cell Functions
Improvement in in vitro T-cell proliferation was assessed upon stimulation with 3 doses of anti-immobilized CD3 (CD3i) monoclonal antibodies ≥1 year after Telethon003 infusion (as compared with pre-GT values) in PBMC and/or T-cell lines. The degree of correction was evaluated with respect to healthy controls.
Measured: Follow up phase - Median duration: 11.1 years (range: 8.01 -13.3 years)
Antigen-specific Responses to Vaccination
The ability to mount a protective humoral response to at least 4 out of 5 nominal antigens including antibodies to T-cell dependent antigens and conjugated or unconjugated polysaccharide antigens was measured after vaccination (planned >1 year after Telethon003 infusion). If results were available on n <5 antigens, the rule of at least n-1 applied to define success.
Measured: Follow up phase - Median duration: 11.1 years (range: 8.01 -13.3 years)
Improved Platelet Count and MPV Normalization
Sustained increase in platelet count compared to baseline, analyzing the individual longitudinal profile
Measured: up to 3 years after Telethon003 infusion
Overall Survival
Participant survival was monitored throughout the study.
Measured: Follow up phase - Median duration: 11.1 years (range: 8.01 -13.3 years)

Secondary outcomes (7)

Lack of Immune Response to Transgene
Anti-WASP and anti-HIV-1 antibodies (anti-p24) were monitored to evaluate response to transgene and to vector, respectively.
Measured: up to 3 years after Telethon003 infusion
Reduced Frequency of Severe Infections
Decrease in number of severe infections as evaluated in the second and third year after the treatment by clinical history, complete physical examinations, hematological and microbiological tests.
Measured: up to 3 years after Telethon003 infusion
Reduced Bruising and Bleeding Episodes
Reduction in bruising and/or bleeding manifestations when present, as assessed by clinical monitoring, compared to clinical history
Measured: 3 years
Reduced Autoimmunity Phenomena and Eczema
Reduction in laboratory markers (number and titer of antibody when available) and/or clinical manifestations of autoimmunity, as evaluated by organ-specific and systemic autoantibodies, imaging and clinical follow-up, compared to clinical history. Reduction in eczema as evaluated by clinical score
Measured: 3 years
Improved Quality of Life
Improved quality of life, measured after the first year of treatment by reduced hospitalization, reduced requirement of drugs, school attendance, social activities.
Measured: 3 year
Multilineage Engraftment of Genetically Corrected Cells
≥0.04 VCN/cell on all the available peripheral blood and/or bone marrow cell subpopulations (BM subpopulations: GlyA+, CD15+, CD61+, CD3+, CD19+, CD56+; PB subpopulations: CD15+, CD19+, CD56+)
Measured: 3 years
Overall Safety of the Treatment
Recording of AE, AR, SAE/SAR, UAR, SUSAR
Measured: 8 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

20 Apr 20104 Oct 2023

First posted24 Jan 2012 (estimated)
Study start20 Apr 2010
Primary completion4 Oct 2023
Study completion4 Oct 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (16)Papers the sponsor has linked to this study.
Other trials for Wiskott-Aldrich Syndrome (WAS)Studies 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
Model description: This will be a single-arm study. All subjects will receive OTL-103 gene therapy and will be followed up for 15 years post gene therapy
Masking: None (open label)
Enrolment: 8 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01515462
Sponsor's protocol ID: 201228
Other IDs: 2009-017346-32, 2009
Acronym: TIGET-WAS
Status last verified: Mar 2025
First submitted: 23 Dec 2011
Last updated: 4 Apr 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

Publications

Aiuti A, Biasco L, Scaramuzza S, Ferrua F, Cicalese MP, Baricordi C, Dionisio F, Calabria A, Giannelli S, Castiello MC, Bosticardo M, Evangelio C, Assanelli A, Casiraghi M, Di Nunzio S, Callegaro L, Benati C, Rizzardi P, Pellin D, Di Serio C, Schmidt M, Von Kalle C, Gardner J, Mehta N, Neduva V, Dow DJ, Galy A, Miniero R, Finocchi A, Metin A, Banerjee PP, Orange JS, Galimberti S, Valsecchi MG, Biffi A, Montini E, Villa A, Ciceri F, Roncarolo MG, Naldini L. Lentiviral hematopoietic stem cell gene therapy in patients with Wiskott-Aldrich syndrome. Science. 2013 Aug 23;341(6148):1233151. doi: 10.1126/science.1233151. Epub 2013 Jul 11.
PubMed 23845947
Aiuti A, Cattaneo F, Galimberti S, Benninghoff U, Cassani B, Callegaro L, Scaramuzza S, Andolfi G, Mirolo M, Brigida I, Tabucchi A, Carlucci F, Eibl M, Aker M, Slavin S, Al-Mousa H, Al Ghonaium A, Ferster A, Duppenthaler A, Notarangelo L, Wintergerst U, Buckley RH, Bregni M, Marktel S, Valsecchi MG, Rossi P, Ciceri F, Miniero R, Bordignon C, Roncarolo MG. Gene therapy for immunodeficiency due to adenosine deaminase deficiency. N Engl J Med. 2009 Jan 29;360(5):447-58. doi: 10.1056/NEJMoa0805817.
PubMed 19179314
Aiuti A, Roncarolo MG. Ten years of gene therapy for primary immune deficiencies. Hematology Am Soc Hematol Educ Program. 2009:682-9. doi: 10.1182/asheducation-2009.1.682.
PubMed 20008254
Bosticardo M, Marangoni F, Aiuti A, Villa A, Grazia Roncarolo M. Recent advances in understanding the pathophysiology of Wiskott-Aldrich syndrome. Blood. 2009 Jun 18;113(25):6288-95. doi: 10.1182/blood-2008-12-115253. Epub 2009 Apr 7.
PubMed 19351959
Boztug K, Dewey RA, Klein C. Development of hematopoietic stem cell gene therapy for Wiskott-Aldrich syndrome. Curr Opin Mol Ther. 2006 Oct;8(5):390-5.
PubMed 17078381
Burns S, Cory GO, Vainchenker W, Thrasher AJ. Mechanisms of WASp-mediated hematologic and immunologic disease. Blood. 2004 Dec 1;104(12):3454-62. doi: 10.1182/blood-2004-04-1678. Epub 2004 Aug 12.
PubMed 15308573
Charrier S, Dupre L, Scaramuzza S, Jeanson-Leh L, Blundell MP, Danos O, Cattaneo F, Aiuti A, Eckenberg R, Thrasher AJ, Roncarolo MG, Galy A. Lentiviral vectors targeting WASp expression to hematopoietic cells, efficiently transduce and correct cells from WAS patients. Gene Ther. 2007 Mar;14(5):415-28. doi: 10.1038/sj.gt.3302863. Epub 2006 Oct 19.
PubMed 17051251
Dupre L, Trifari S, Follenzi A, Marangoni F, Lain de Lera T, Bernad A, Martino S, Tsuchiya S, Bordignon C, Naldini L, Aiuti A, Roncarolo MG. Lentiviral vector-mediated gene transfer in T cells from Wiskott-Aldrich syndrome patients leads to functional correction. Mol Ther. 2004 Nov;10(5):903-15. doi: 10.1016/j.ymthe.2004.08.008.
PubMed 15509508
Follenzi A, Sabatino G, Lombardo A, Boccaccio C, Naldini L. Efficient gene delivery and targeted expression to hepatocytes in vivo by improved lentiviral vectors. Hum Gene Ther. 2002 Jan 20;13(2):243-60. doi: 10.1089/10430340252769770.
PubMed 11812281
Galy A, Roncarolo MG, Thrasher AJ. Development of lentiviral gene therapy for Wiskott Aldrich syndrome. Expert Opin Biol Ther. 2008 Feb;8(2):181-90. doi: 10.1517/14712598.8.2.181.
PubMed 18194074
Marangoni F, Bosticardo M, Charrier S, Draghici E, Locci M, Scaramuzza S, Panaroni C, Ponzoni M, Sanvito F, Doglioni C, Liabeuf M, Gjata B, Montus M, Siminovitch K, Aiuti A, Naldini L, Dupre L, Roncarolo MG, Galy A, Villa A. Evidence for long-term efficacy and safety of gene therapy for Wiskott-Aldrich syndrome in preclinical models. Mol Ther. 2009 Jun;17(6):1073-82. doi: 10.1038/mt.2009.31. Epub 2009 Mar 3.
PubMed 19259069
Villa A, Notarangelo L, Macchi P, Mantuano E, Cavagni G, Brugnoni D, Strina D, Patrosso MC, Ramenghi U, Sacco MG, et al. X-linked thrombocytopenia and Wiskott-Aldrich syndrome are allelic diseases with mutations in the WASP gene. Nat Genet. 1995 Apr;9(4):414-7. doi: 10.1038/ng0495-414.
PubMed 7795648
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 42777242
Quaranta 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
Scala S, Ferrua F, Basso-Ricci L, Dionisio F, Omrani M, Quaranta P, Jofra Hernandez R, Del Core L, Benedicenti F, Monti I, Giannelli S, Fraschetta F, Darin S, Albertazzi E, Galimberti S, Montini E, Calabria A, Cicalese MP, Aiuti A. Hematopoietic reconstitution dynamics of mobilized- and bone marrow-derived human hematopoietic stem cells after gene therapy. Nat Commun. 2023 May 27;14(1):3068. doi: 10.1038/s41467-023-38448-y.
PubMed 37244942

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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All Wiskott-Aldrich Syndrome (WAS) trials

Study at a glance

From the registry record, last updated by the sponsor on 4 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I/II Clinical Trial of Hematopoietic Stem Cell Gene Therapy for the Wiskott-Aldrich Syndrome
ClinicalTrials.gov ID: NCT01515462
Acronym / sponsor ID: TIGET-WAS / 201228
Conditions: Wiskott-Aldrich Syndrome (WAS)
Keywords: Lentiviral vector, Gene therapy, Wiskott-Aldrich Syndrome, TLT003, Previously GSK2696275, Previously OTL-103
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 8 participants (actual)
Lead sponsor: Fondazione TelethonUniversity, hospital or other
Collaborators: Ospedale San Raffaele
Study start: 20 Apr 2010 (actual)
Primary completion: 4 Oct 2023 (actual)
Study completion: 4 Oct 2023 (actual)
First posted: 24 Jan 2012 (estimated)
Results: Posted 4 Apr 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This is phase I/II protocol to evaluate the safety and efficacy of WAS gene transfer into hematopoietic stem/progenitor cells for the treatment of Wiskott Aldrich Syndrome.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: This will be a single-arm study. All subjects will receive OTL-103 gene therapy and will be followed up for 15 years post gene therapy

Arm	Type	Receives
TLT003 gene therapy	Experimental	Genetic: TLT003Eligible subjects will receive intravenous (IV) infusion of TLT003 gene therapy. Subjects affected by WAS who don't have a suitable matched donor for allogenic hematopoietic stem cell transplantation will be included

Who may qualify

Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (8 listed)

Diagnosis of WAS defined by genetic mutation and at least one of the following criteria:
No HLA-identical sibling donor
Negative search for a matched unrelated donor (10/10) or an adequate unrelated cord blood donor (5-6/6) within 4-6 months
Parental/guardian/patient signed informed consent.

Key exclusion criteria (6 listed)

Patients positive for HIV-infection.
Patients affected by neoplasia.
Patients with cytogenetic alterations typical of MDS/AML.
Patients with end-organ functions or any other severe disease which, in the judgement of the investigator, would make the patient inappropriate for entry into this study.
Patients who underwent an allogeneic haematopoietic stem cell transplantation in the previous 6 months.

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
TLT003Also: Previously GSK2696275, Previously OTL-103TLT003 is an autologous CD34+ cells collected from bone marrow and/or peripheral blood and transduced with a lentiviral vector encoding Wiskott-Aldrich syndrome (WAS) protein	Genetic	TLT003 gene therapy

Primary outcome

Safety of Reduced Conditioning Regimen
Time frame: Follow up phase - Median duration: 11.1 years (range: 8.01 -13.3 years)
The absence of prolonged aplasia (defined as ANC <0.5×10^9/L [<500/μL] at Day +60, with no evidence of BM recovery and requiring backup administration) was assumed as demonstrating the safety of the RIC regimen.
Safety of Lentivirus Gene Transfer Into HSC
Time frame: after 48 hours after Telethon003 infusion
Safety and tolerability of lentiviral-transduced cell infusion. This will be evaluated on the basis of adverse events reporting and monitoring of the systemic reactions to cell infusion.
Sustained Engraftment of Genetically Corrected Haematopoietic Stem Cells in Peripheral Blood and/or in Bone Marrow
Time frame: at 1 year after Telethon003 infusion
Engraftment is characterized by the presence of gene modified cells in the BM or PB compartments. The main indicator of gene correction is detection of the WAS LVV sequences in the HSPCs and their progeny. The VCN, which is the mean number of integrated copies of the vector sequences per cell genome, was measured using PCR-based methods in DNA samples extracted from BM and PB cell populations at various timepoints post-treatment. Adequate engraftment was defined as either ≥0.04 VCN/cell in BM CD34+ cells or ≥0.01 VCN/cell in PB CD3+ cells.
Presence of Detectable Vector-derived WASP
Time frame: Median duration: 11.1 years (range: 8.01 -13.3 years)
The percentage of subjects who present the proportion of PB cells expressing WASP was assessed by flow cytometry analysis.
Improved T-cell Functions
Time frame: Follow up phase - Median duration: 11.1 years (range: 8.01 -13.3 years)
Improvement in in vitro T-cell proliferation was assessed upon stimulation with 3 doses of anti-immobilized CD3 (CD3i) monoclonal antibodies ≥1 year after Telethon003 infusion (as compared with pre-GT values) in PBMC and/or T-cell lines. The degree of correction was evaluated with respect to healthy controls.
Antigen-specific Responses to Vaccination
Time frame: Follow up phase - Median duration: 11.1 years (range: 8.01 -13.3 years)
The ability to mount a protective humoral response to at least 4 out of 5 nominal antigens including antibodies to T-cell dependent antigens and conjugated or unconjugated polysaccharide antigens was measured after vaccination (planned >1 year after Telethon003 infusion). If results were available on n <5 antigens, the rule of at least n-1 applied to define success.
Improved Platelet Count and MPV Normalization
Time frame: up to 3 years after Telethon003 infusion
Sustained increase in platelet count compared to baseline, analyzing the individual longitudinal profile
Overall Survival
Time frame: Follow up phase - Median duration: 11.1 years (range: 8.01 -13.3 years)
Participant survival was monitored throughout the study.

7 secondary outcomes

Lack of Immune Response to Transgene
Time frame: up to 3 years after Telethon003 infusion
Reduced Frequency of Severe Infections
Time frame: up to 3 years after Telethon003 infusion
Reduced Bruising and Bleeding Episodes
Time frame: 3 years
Reduced Autoimmunity Phenomena and Eczema
Time frame: 3 years
Improved Quality of Life
Time frame: 3 year
Multilineage Engraftment of Genetically Corrected Cells
Time frame: 3 years
Overall Safety of the Treatment
Time frame: 8 years

Results and safety

Results posted to the registry on 4 Apr 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
OTL-103 Gene Therapy	8	8

Primary outcome: Safety of Reduced Conditioning Regimen

Time frame: Follow up phase - Median duration: 11.1 years (range: 8.01 -13.3 years). Count of participants. Unit: Participants

Measure	TLT003 Gene Therapy n = 8
Value	8

Population analysed: Mobilization Set (MS) for Safety analysis. Intent-to-treat (ITT) population for Efficacy analysis. All eight enrolled participants were included in the ITT and MS populations

Primary outcome: Safety of Lentivirus Gene Transfer Into HSC

Time frame: after 48 hours after Telethon003 infusion. Count of participants. Unit: Participants

Measure	TLT003 Gene Therapy n = 8
Value	8

Primary outcome: Sustained Engraftment of Genetically Corrected Haematopoietic Stem Cells in Peripheral Blood and/or in Bone Marrow

Time frame: at 1 year after Telethon003 infusion. Count of participants. Unit: Participants

Measure	TLT003 Gene Therapy n = 8
Value	8

Population analysed: count of participants with sustained engraftment of genetically corrected HSPCs

Primary outcome: Presence of Detectable Vector-derived WASP

Time frame: Median duration: 11.1 years (range: 8.01 -13.3 years). Count of participants. Unit: Participants

Measure	TLT003 Gene Therapy n = 8
Value	8

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were reported in the statistical outputs from Screening onward. Post-treatment AEs were recorded during follow up - Median duration of follow-up was 11.1 (range: 8.0-13.3) years.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
OTL-103 Gene Therapy	8 of 8 (100%)	8 of 8 (100%)	0 of 8

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 23845947Aiuti A, Biasco L, Scaramuzza S, Ferrua F, Cicalese MP, Baricordi C, Dionisio F, Calabria A, Giannelli S, Castiello MC, Bosticardo M, Evangelio C, Assanelli A, Casiraghi M, Di Nunzio S, Callegaro L, Benati C, Rizzardi P, Pellin D, Di Serio C, Schmidt M, Von Kalle C, Gardner J, Mehta N, Neduva V, Dow DJ, Galy A, Miniero R, Finocchi A, Metin A, Banerjee PP, Orange JS, Galimberti S, Valsecchi MG, Biffi A, Montini E, Villa A, Ciceri F, Roncarolo MG, Naldini L. Lentiviral hematopoietic stem cell gene therapy in patients with Wiskott-Aldrich syndrome. Science. 2013 Aug 23;341(6148):1233151. doi: 10.1126/science.1233151. Epub 2013 Jul 11.
Background: PubMed 19179314Aiuti A, Cattaneo F, Galimberti S, Benninghoff U, Cassani B, Callegaro L, Scaramuzza S, Andolfi G, Mirolo M, Brigida I, Tabucchi A, Carlucci F, Eibl M, Aker M, Slavin S, Al-Mousa H, Al Ghonaium A, Ferster A, Duppenthaler A, Notarangelo L, Wintergerst U, Buckley RH, Bregni M, Marktel S, Valsecchi MG, Rossi P, Ciceri F, Miniero R, Bordignon C, Roncarolo MG. Gene therapy for immunodeficiency due to adenosine deaminase deficiency. N Engl J Med. 2009 Jan 29;360(5):447-58. doi: 10.1056/NEJMoa0805817.
Background: PubMed 20008254Aiuti A, Roncarolo MG. Ten years of gene therapy for primary immune deficiencies. Hematology Am Soc Hematol Educ Program. 2009:682-9. doi: 10.1182/asheducation-2009.1.682.
Background: PubMed 19351959Bosticardo M, Marangoni F, Aiuti A, Villa A, Grazia Roncarolo M. Recent advances in understanding the pathophysiology of Wiskott-Aldrich syndrome. Blood. 2009 Jun 18;113(25):6288-95. doi: 10.1182/blood-2008-12-115253. Epub 2009 Apr 7.
Background: PubMed 17078381Boztug K, Dewey RA, Klein C. Development of hematopoietic stem cell gene therapy for Wiskott-Aldrich syndrome. Curr Opin Mol Ther. 2006 Oct;8(5):390-5.
Background: PubMed 15308573Burns S, Cory GO, Vainchenker W, Thrasher AJ. Mechanisms of WASp-mediated hematologic and immunologic disease. Blood. 2004 Dec 1;104(12):3454-62. doi: 10.1182/blood-2004-04-1678. Epub 2004 Aug 12.
Background: PubMed 17051251Charrier S, Dupre L, Scaramuzza S, Jeanson-Leh L, Blundell MP, Danos O, Cattaneo F, Aiuti A, Eckenberg R, Thrasher AJ, Roncarolo MG, Galy A. Lentiviral vectors targeting WASp expression to hematopoietic cells, efficiently transduce and correct cells from WAS patients. Gene Ther. 2007 Mar;14(5):415-28. doi: 10.1038/sj.gt.3302863. Epub 2006 Oct 19.
Background: PubMed 15509508Dupre L, Trifari S, Follenzi A, Marangoni F, Lain de Lera T, Bernad A, Martino S, Tsuchiya S, Bordignon C, Naldini L, Aiuti A, Roncarolo MG. Lentiviral vector-mediated gene transfer in T cells from Wiskott-Aldrich syndrome patients leads to functional correction. Mol Ther. 2004 Nov;10(5):903-15. doi: 10.1016/j.ymthe.2004.08.008.
Background: PubMed 11812281Follenzi A, Sabatino G, Lombardo A, Boccaccio C, Naldini L. Efficient gene delivery and targeted expression to hepatocytes in vivo by improved lentiviral vectors. Hum Gene Ther. 2002 Jan 20;13(2):243-60. doi: 10.1089/10430340252769770.
Background: PubMed 18194074Galy A, Roncarolo MG, Thrasher AJ. Development of lentiviral gene therapy for Wiskott Aldrich syndrome. Expert Opin Biol Ther. 2008 Feb;8(2):181-90. doi: 10.1517/14712598.8.2.181.
Background: PubMed 19259069Marangoni F, Bosticardo M, Charrier S, Draghici E, Locci M, Scaramuzza S, Panaroni C, Ponzoni M, Sanvito F, Doglioni C, Liabeuf M, Gjata B, Montus M, Siminovitch K, Aiuti A, Naldini L, Dupre L, Roncarolo MG, Galy A, Villa A. Evidence for long-term efficacy and safety of gene therapy for Wiskott-Aldrich syndrome in preclinical models. Mol Ther. 2009 Jun;17(6):1073-82. doi: 10.1038/mt.2009.31. Epub 2009 Mar 3.
Background: PubMed 7795648Villa A, Notarangelo L, Macchi P, Mantuano E, Cavagni G, Brugnoni D, Strina D, Patrosso MC, Ramenghi U, Sacco MG, et al. X-linked thrombocytopenia and Wiskott-Aldrich syndrome are allelic diseases with mutations in the WASP gene. Nat Genet. 1995 Apr;9(4):414-7. doi: 10.1038/ng0495-414.

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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.

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 TLT003 in people with Wiskott-Aldrich Syndrome (WAS), run by Fondazione Telethon at 1 site in Italy.

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 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 4 Apr 2025. 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 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 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?

Yes. Results are posted in the registry (first posted 4 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Safety of Reduced Conditioning Regimen (time frame: Follow up phase - Median duration: 11.1 years (range: 8.01 -13.3 years)). The study lists 8 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 NCT01515462, which also lists 16 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 4 Apr 2025.