Gene Therapy for Leukocyte Adhesion Deficiency-I (LAD-I):A Phase I/II Clinical Trial to Evaluate the Safety and Efficacy of the Infusion of Autologous Hematopoietic Stem Cells Transduced with a Lentiviral Vector Encoding the ITGB2 Gene

Phase 1

• Conditions: eukocyte Adhesion Deficiency-I (LAD-I); MedDRA version: 20.0Level: LLTClassification code 10018137Term: Genetic anomalies of leukocytesSystem Organ Class: 100000004850; Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

• Registration Number: EUCTR2020-000517-33-GB
• Lead Sponsor: Rocket Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-02-21
• Last Update Posted: 13 October 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 9

Inclusion Criteria

1. A confirmed diagnosis of severe LAD-I as demonstrated by flow cytometry indicating CD18 expression on <2% neutrophils (PMNs). Subjects in which CD18+ PMNs are >2% will be considered eligible with <2% CD11a or CD11b expressing PMNs and if there is a documented ITGB2 mutation and clinical history consistent with LAD-I (or known family history).
2. At least one (1) prior significant bacterial or fungal infection (US NCI CTCAE v5.0, Grade =2). This criterion is not required for subjects with documented family history who meet the above inclusion criteria.
3. Age =3 months.
4. Considered to be an appropriate candidate for autologous transplantation of HSCs.
5. A competent custodial parent with legal capacity to execute an IRB/EC-approved consent form must be available to participate in the consent process. (Informed assent will be sought from capable subjects, in accordance with the directive of the IRB/EC and with local requirements.)
6. Ability to comply with trial procedures including investigational therapy and follow up evaluations.
Are the trial subjects under 18? yes
Number of subjects for this age range: 9
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Availability of a medically-eligible HLA-identical sibling donor transplant. Subjects may not be included in this trial as an alternative to a clinically-indicated and feasible HLA-matched sibling donor HSCT. If an HLA-identical sibling is identified, but mPB or BM HSC collection is not feasible (for example: donor is in utero, is a newborn from whom cord blood was not collected, or is unable to undergo donation procedure because of medical impairments), then inclusion may be permitted per Investigator discretion.
2. Hepatic dysfunction as defined by either:
• Bilirubin >1.5× the ULN or
• ALT or AST >2.5×ULN
3. Renal dysfunction as defined by either Grade 3 or higher abnormalities in serum sodium, potassium, calcium, magnesium or phosphate as defined by NCI CTCAE v5.0, or the requirement for either peritoneal dialysis or hemodialysis.
4. Pulmonary dysfunction as defined by either:
• need for supplemental oxygen during the prior 2 weeks (in absence of acute infection).
• Oxygen saturation (by pulse oximetry) <90%.
5. Evidence of active metastatic or locoregionally advanced malignancy (including hematologic malignancy) for which survival is anticipated to be less than 3 years.
6. Serious infections with persistent bloodstream pathogens at time of trial entry. (Subjects with active infections (e.g., unresolved ulcerative lesions, skin or oral infections) are permitted as long as appropriate antibiotic therapy has been (or is
being) administered.)
7. Any medical or other contraindication for both leukapheresis and BM harvest procedure, as determined by the treating Investigator.
8. Any medical or other contraindication for the administration of conditioning therapy, as determined by the treating Investigator.
9. Significant medical conditions, including documented HIV infection, poorly controlled diabetes, poorly-controlled hypertension, poorly-controlled cardiac arrhythmia or congestive heart failure; or arterial thromboembolic events (including stroke or myocardial infarction) within the 6 prior months.
10. Any medical or psychiatric condition that in the opinion of the Investigator renders the subject unfit for trial participation or at higher than acceptable risk for participation.
Subjects who are evaluated for the trial and determined ineligible may be subsequently evaluated and declared eligible if the criteria by which they were considered ineligible is reversible (e.g., bloodstream infection, transient increase in liver enzymes) and there is documented and plausible evidence of its resolution in the opinion of the principal investigator.

Study & Design

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