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Gene Therapy for Wiskott-Aldrich Syndrome
Phase 1, PHASE2 trial testing TLT003 in Wiskott-Aldrich Syndrome (WAS) in 8 participants. Completed in 4 October 2023.
| Lead sponsor | Fondazione Telethon |
|---|---|
| Phase | Phase 1, PHASE2 |
| Status | Completed |
| Study type | INTERVENTIONAL |
| Allocation | na |
| Design | single group |
| Masking | none |
| Primary purpose | treatment |
| Enrollment | 8 |
| Start date | 20 April 2010 |
| Primary completion | 4 October 2023 |
| Estimated completion | 4 October 2023 |
| Sites | 1 location across Italy |
Fondazione Telethon — full company profile →
Eligibility, any sex, with Wiskott-Aldrich Syndrome (WAS). Patients with the condition only — healthy volunteers not accepted.
Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.
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.
| Group | Value | 95% CI |
|---|---|---|
| TLT003 Gene Therapy | 8 |
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.
| Group | Value | 95% CI |
|---|---|---|
| TLT003 Gene Therapy | 8 |
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.
| Group | Value | 95% CI |
|---|---|---|
| TLT003 Gene Therapy | 8 |
The percentage of subjects who present the proportion of PB cells expressing WASP was assessed by flow cytometry analysis.
| Group | Value | 95% CI |
|---|---|---|
| TLT003 Gene Therapy | 8 |
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.
| Group | Value | 95% CI |
|---|---|---|
| TLT003 Gene Therapy | 8 |
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.
| Group | Value | 95% CI |
|---|---|---|
| TLT003 Gene Therapy | 7 |
Sustained increase in platelet count compared to baseline, analyzing the individual longitudinal profile
| Group | Value | 95% CI |
|---|---|---|
| TLT003 Gene Therapy | 8 |
Participant survival was monitored throughout the study.
| Group | Value | 95% CI |
|---|---|---|
| TLT003 Gene Therapy | 8 |
Anti-WASP and anti-HIV-1 antibodies (anti-p24) were monitored to evaluate response to transgene and to vector, respectively.
| Group | Value | 95% CI |
|---|---|---|
| TLT003 Gene Therapy | 8 |
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.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.
| Reaction | System | OTL-103 Gene Therapy |
|---|---|---|
| Pyrexia | General disorders | — |
| Device related infection | Infections and infestations | — |
| Mesenteric lymphadenitis | Blood and lymphatic system disorders | — |
| Neutropenia | Blood and lymphatic system disorders | — |
| Vomiting | Gastrointestinal disorders | — |
| Food Allergy | Immune system disorders | — |
| Gastroenteritis | Infections and infestations | — |
| Pneumonia aspiration | Infections and infestations | — |
| Appendicitis | Infections and infestations | — |
| Aspergillus infection | Infections and infestations | — |
| Bacterial sepsis | Infections and infestations | — |
| Cellulitis | Infections and infestations | — |
| Device related sepsis | Infections and infestations | — |
| Gastroenteritis rotavirus | Infections and infestations | — |
| Influenza | Infections and infestations | — |
| Otitis media | Infections and infestations | — |
| Pneumonia bacterial | Infections and infestations | — |
| Tooth Abscess | Infections and infestations | — |
| Tracheitis | Infections and infestations | — |
| Viral infection | Infections and infestations | — |
| Head injury | Injury, poisoning and procedural complications | — |
| Electrolyte imbalance | Metabolism and nutrition disorders | — |
| Papillary thyroid cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | — |
| Irritability | Psychiatric disorders | — |
| Reaction | System | OTL-103 Gene Therapy |
|---|---|---|
| Pyrexia | General disorders | — |
| Upper respiratory tract infection | Infections and infestations | — |
| Anti-platelet antibody positive | Investigations | — |
| Diarrhoea | Gastrointestinal disorders | — |
| Petechiae | Skin and subcutaneous tissue disorders | — |
| Rhinitis | Infections and infestations | — |
| Hypokalaemia | Metabolism and nutrition disorders | — |
| Eczema | Skin and subcutaneous tissue disorders | — |
| Ear infection | Infections and infestations | — |
| Influenza | Infections and infestations | — |
| Staphylococcus test positive | Investigations | — |
| Antineutrophil cytoplasmic antibody positive | Investigations | — |
| Iron deficiency | Metabolism and nutrition disorders | — |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | — |
| Cough | Respiratory, thoracic and mediastinal disorders | — |
| Haematochezia | Gastrointestinal disorders | — |
| Dental caries | Gastrointestinal disorders | — |
| Anal fissure | Gastrointestinal disorders | — |
| Malocclusion | Gastrointestinal disorders | — |
| Otitis media acute | Infections and infestations | — |
| Pharyngitis | Infections and infestations | — |
| Conjunctivitis | Infections and infestations | — |
| Respiratory tract infection | Infections and infestations | — |
| Sinusitis | Infections and infestations | — |
| Pneumonia | Infections and infestations | — |
| Coronavirus infection | Infections and infestations | — |
| Limb injury | Injury, poisoning and procedural complications | — |
| Streptococcus test positive | Investigations | — |
| Blood immunoglonulin E increased | Investigations | — |
| Rash | Skin and subcutaneous tissue disorders | — |
| Dermatitis | Skin and subcutaneous tissue disorders | — |
| Phimosis | Congenital, familial and genetic disorders | — |
| Eye inflammation | Eye disorders | — |
| Vomiting | Gastrointestinal disorders | — |
| Mouth haemorrhage | Gastrointestinal disorders | — |
| Diarrhoea haemorrhagic | Gastrointestinal disorders | — |
| Constipation | Gastrointestinal disorders | — |
| Allergy to immunoglobulin therapy | Immune system disorders | — |
| Otitis media | Infections and infestations | — |
| Gastroenteritis | Infections and infestations | — |
Most-reported serious reactions: Pyrexia, Device related infection, Mesenteric lymphadenitis, Neutropenia, Vomiting, Food Allergy, Gastroenteritis, Pneumonia aspiration.
Data from ClinicalTrials.gov NCT01515462 adverse events section.
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.
8 peer-reviewed publications reference this trial (live from Europe PMC):
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Trials by the same sponsor.
Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT01515462.
Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing