Gene therapy study using a frozen formulation of OTL-103 in patients with Wiskott-Aldrich Syndrome (WAS)

Phase 1

• Conditions: Wiskott-Aldrich Syndrome; MedDRA version: 20.0Level: PTClassification code 10061598Term: ImmunodeficiencySystem Organ Class: 10021428 - Immune system disorders; Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: EUCTR2018-003842-18-IT
• Lead Sponsor: Orchard Therapeutics Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-11-19
• Last Update Posted: 9 September 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Male
• Target Recruitment: 6

Inclusion Criteria

•Age: up to 65 years.
• 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);
Family member affected by WAS with life-threatening or fatal clinical events.
• No human leukocyte antigen (HLA)-identical related donor available.
• Parental/guardian/subject-signed informed consent, and subject assent (if appropriate).
•For all subjects in the reproductive age range, agreement to use highly
effective and adequate method of contraception (as detailed in Appendix 4: Contraceptive Guidance and Collection of Pregnancy Information) while receiving treatment and for at least 12 months following drug administration.
Are the trial subjects under 18? yes
Number of subjects for this age range: 6
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

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 patient inappropriate for entry into this study.
In addition to the potential infections tested per protocol, the PI should Tissue Directive as clinically appropriate and discuss the results with the medical monitor prior to cell harvest.
Patients with ALT >2x upper limit of normal (ULN) or total bilirubin >1.5 x ULN may be included only after discussed and agreed with the medical monitor and considered in the context of the criterion for excluding patients with other severe disease.
Isolated elevation of total bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35% of total.
2. Malignant neoplasia (except local skin cancer) or a documented history of hereditary cancer syndrome . Patients 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.
3. Myelodysplasia, cytogenetic alterations characteristic of myelodysplastic syndrome and acute myeloid leukaemia , or other serious haematological disorders.
4. Prior allogeneic hematopoietic stem cell transplantation, with evidence of residual cells of donor origin.
5. Documented HIV infection (positive HIV RNA and/or anti-p24 antibodies).
6. Current participation in other interventional clinical trials.
7. Previous gene therapy.
8. Symptomatic herpes zoster, not responsive to specific treatment.
Patients with a recent history of herpes zoster may be included in the study. In such cases, inclusion, additional monitoring and treatment of the condition must be discussed and approved by the medical monitor.
9. Evidence of active tuberculosis (TB) based upon medical examination, chest imaging and TB testing i.e. QuantiFERON®-TB Gold test and microbiological evidence.
Patients with latent TB, as documented by medical history and/or TB testing may be included in the study if receiving antibiotic prophylaxis (e.g. isoniazid). Inclusion, monitoring and treatment of TB in such patients must be discussed and approved by the medical monitor.
10. Acute or chronic stable Hepatitis B as evidenced by positive Hepatitis B surface antigen (HBsAg) test result at screening or within 3 months prior to start of conditioning and/or positive HBV DNA.
Patients with positive Hepatitis B core antibody due to prior resolved disease may be eligible to be included, only if a confirmatory negative HBsAg and negative Hepatitis B DNA test are obtained. Inclusion, monitoring and treatment of hepatitis in such patients must be discussed and approved by the medical monitor.
11. Presence of positive Hepatitis C RNA test result at screening. Patients who have previously tested positive for HCV can be treated, provided they demonstrate absence of ongoing infection using a nucleic acid test with a limit of quantification of =15 international units/mL.
Negative test results are required on at least 3 sequential occasions over a period of at least 4 weeks, after completion of treatment for hepatitis C, with the final test conducted no more than 3 days prior to cell harvest.
Inclusion, monitoring and treatment of hepatitis in such subjects must be discussed and approved by the medical monitor.
12. Patients that are not eligible for mobilisation protocols in order to obtain CD34+ cells f

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified