A Gene Therapy Trial to Evaluate the Safety and Efficacy of RP-L201 in Subjects With Leukocyte Adhesion Deficiency-I

• Register: ClinicalTrials.gov
• Last refreshed on: 22 March 2021
• Main ID: NCT03825783
• Date of registration: 25/01/2019
• Prospective Registration: Yes
• Primary sponsor: Rocket Pharmaceuticals Inc.
• Public title: A Gene Therapy Trial to Evaluate the Safety and Efficacy of RP-L201 in Subjects With Leukocyte Adhesion Deficiency-I
• Scientific title: Gene Therapy for Leukocyte Adhesion Deficiency-I (LAD-I): A Phase I 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.
• Date of first enrolment: April 15, 2019
• Target sample size: 2
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/show/NCT03825783
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Spain

Contacts

• Name: Julián Sevilla Navarro, MD, PhD
• Affiliation: Hospital Infantil Universitario Niño Jesús (HIUNJ)

• Name: LAD Clinical Trial

Key inclusion & exclusion criteria

Inclusion Criteria:

- A confirmed diagnosis of severe LAD-I as demonstrated by flow cytometry indicating
CD18 expression on <2% neutrophils (polymorphonuclear neutrophils [PMNs]). (Patients
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).

- At least one (1) prior significant bacterial or fungal infection (US National Cancer
Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], v5.0, Grade
=2). This criteria is not required for patients with documented family history who
meet the above inclusion criteria.

- Age =3 months.

- Considered to be an appropriate candidate for autologous transplantation of HSCs.

- A competent custodial parent with legal capacity to execute an Ethics Committee
(EC)-approved consent form must be available to participate in the consent process.
(Informed assent will be sought from capable patients, in accordance with the
directive of the EC and with local requirements.)

- Ability to comply with trial procedures including investigational therapy and
follow-up evaluations.

Exclusion Criteria:

- Availability of a medically-eligible human leukocyte antigen (HLA)-identical sibling
donor transplant. Patients may not be included in this trial as an alternative to a
clinically-indicated and feasible HLA-matched sibling donor HSC transplant. If an
HLA-identical sibling is identified, but mobilized peripheral blood or bone marrow 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 the Principal Investigator
discretion.

- Hepatic dysfunction as defined by either:

- Bilirubin > 1.5 × the upper limit of normal (ULN) or

- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5×ULN

- 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%.

- Evidence of active metastatic or locoregionally advanced malignancy (including
hematologic malignancy) for which survival is anticipated to be less than 3 years.

- Serious infections with persistent bloodstream pathogens at time of trial entry.
(Patients 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).

- Any medical or other contraindication for both leukopheresis and bone marrow harvest
procedure, as determined by the treating investigator.

- Any medical or other contraindication for the administration of conditioning therapy,
as determined by the treating investigator.

- Significant medical conditions, including documented human immunodeficiency virus
(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.

- Any medical or psychiatric condition that in the opinion of the Principal Investigator
renders the patient unfit for trial participation or at higher than acceptable risk
for participation.

Patients 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 (for example: bloodstream infection, transient increase in liver enzymes) and
there is documented and plausible evidence of its resolution in the opinion of the
Principal Investigator.



Age minimum: 3 Months
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Leukocyte Adhesion Defect - Type I

Intervention(s)

Biological: RP-L201

Primary Outcome(s)

Number of participants with treatment-related adverse events as assessed by United States (US) National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v.5.0 [Time Frame: 2 years]

Survival following infusion of RP-L201 [Time Frame: 2 years]

Secondary Outcome(s)

CD18 expression after infusion of RP-L201 [Time Frame: 2 years]

Assessment of number of participants with a change in skin lesions or periodontal abnormalities after infusion of RP-L201 [Time Frame: 2 years]

Assessment of overall survival after infusion of RP-L201 [Time Frame: 2 years]

Genetic correction after infusion of RP-L201 [Time Frame: 6 months]

Assessment of number of participants with a change in LAD-I-associated neutrophilia after infusion of RP-L201 [Time Frame: 2 years]

Incidence of infections after infusion of RP-L201 [Time Frame: 2 years]

Secondary ID(s)

RP-L201-0218

Source(s) of Monetary Support

Please refer to primary and secondary sponsors