A Clinical Study to Evaluate the Use of a Cryopreserved Formulation of OTL-103 in Subjects with WAS.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione Telethon Ets

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

29 Oct 2024 → ongoing

Decision date (initial)

2024-10-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Fondazione Telethon ETS

External identifiers

EU CT number

2024-517792-20-00

EudraCT number

2018-003842-18

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

• To evaluate the clinical efficacy of the cryopreserved formulation of OTL-103 at 12 months for bleeding events and from 6 to 18 months for severe infections

Secondary objectives 1

1. • To evaluate the overall survival at 12, 24 and 36 months • To evaluate the engraftment at 6 months • To evaluate the safety of treatment with OTL-103 • To evaluate the biological efficacy of the cryopreserved formulation of OTL- 103 at 12 months, 2 years and 3 years • To evaluate the clinical efficacy of the cryopreserved formulation of OTL- 103 at 2 and 3 years • To evaluate sustained engraftment of the cryopreserved formulation of OTL- 103 at 2 and 3 years • To evaluate the immunological function after treatment with OTL-103 up to 3 years • To evaluate the effect of OTL-103 on health-related quality of life at 1, 2 and 3 years

Conditions and MedDRA coding

Wiskott-Aldrich Syndrome

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-107868-PIP20-16

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. Diagnosis of WAS defined by genetic mutation and at least one of the following criteria: severe WASP mutation; absent WASP expression; severe clinical score (Zhu clinical score ≥ 3); • No human leukocyte antigen (HLA)-identical related donor available.

Exclusion criteria 1

1. • 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 subject inappropriate for entry into this study. • Malignant neoplasia (except local skin cancer) or a documented history of hereditary cancer syndrome (detected via medical history check during screening). Subjects with a prior successfully treated malignancy and a sufficient follow-up to exclude recurrence (based on oncologist opinion) can be included after discussion and approval by the Medical Monitor. • Myelodysplasia, cytogenetic alterations characteristic of myelodysplastic syndrome and acute myeloid leukemia, or other serious hematological disorders. • Prior allogeneic hematopoietic stem cell transplantation, with evidence of residual cells of donor origin. • Previous gene therapy. • Documented human immunodeficiency virus (HIV) infection (positive HIV ribonucleic acid and/or anti-p24 antibodies).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Evaluation of the clinical efficacy: • annualized rate of severe infections from 6 to 18 months after gene therapy (GT) compared with 1 year prior to GT; • annualized rate of moderate and severe bleeding episodes up to 1 year after GT compared with 1 year prior to GT.

Secondary endpoints 1

1. • Evaluation of the overall survival at 12, 24 and 36 months • Evaluation of the safety of treatment: 1) safety and tolerability as measured by adverse event (AE) reporting; 2) absence of malignancy or abnormal clonal proliferation (ACP) development due to insertional oncogenesis; 3) absence of replication-competent lentivirus (RCL). • Evaluation of the engraftment at 6 months • Evaluation of biological correlates of efficacy at 12 months, 2 years and 3 years

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione Telethon Ets

Sponsor organisation

Fondazione Telethon Ets

Address

Via Varese 16 B

City

Rome

Postcode

00185

Country

Italy

Scientific contact point

Organisation

Fondazione Telethon Ets

Contact name

Elena Tomasetto

Public contact point

Organisation

Fondazione Telethon Ets

Contact name

Elena Tomasetto

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications