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

NCT03825783 | Withdrawn Phase 1 DMC

• 1 other identifier: RP-L201-0218
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The primary purpose of the Phase I portion of the study is to determine the safety profile and preliminary evidence of efficacy associated with infusion of autologous gene-corrected hematopoietic stem cells.

Conditions

Leukocyte Adhesion Defect - Type I

Keywords

Leukocyte Adhesion Deficiency- Type I; LAD-I

Outcome Measures

Primary Outcomes (2)

• 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

  Evaluation of safety associated with treatment with RP-L201

  2 years

• Survival following infusion of RP-L201

  Evaluation of survival as determined by the proportion of subjects alive at age 2 (24 months) and at least 1-year post infusion without allogeneic hematopoietic stem cell transplant

  2 years

Secondary Outcomes (6)

• CD18 expression after infusion of RP-L201

  2 years

• Genetic correction after infusion of RP-L201

  6 months

• Incidence of infections after infusion of RP-L201

  2 years

• Assessment of number of participants with a change in LAD-I-associated neutrophilia after infusion of RP-L201

  2 years

• Assessment of number of participants with a change in skin lesions or periodontal abnormalities after infusion of RP-L201

  2 years

Study Arms (1)

RP-L201

EXPERIMENTAL

RP-L201 is a gene therapy product containing autologous genetically modified CD34+ hematopoietic stem cells transduced with Chim-CD18-WPRE lentiviral vector administered as a single infusion in subjects with severe LAD-I

Biological: RP-L201

Interventions

RP-L201 BIOLOGICAL

CD34+ enriched hematopoietic stem cells from subjects with severe LAD-I transduced ex vivo with lentiviral vector carrying the ITGB2 gene, Chim-CD18-WPRE.

RP-L201

Eligibility Criteria

• Age: 3 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Rocket Pharmaceuticals Inc.: lead

Study Sites (1)

Hospital Infantil Universitario Niño Jesús (HIUNJ)

Madrid, 28009, Spain

Location

MeSH Terms

Conditions

Leukocyte adhesion deficiency type 1

Study Officials

• Julián Sevilla Navarro, MD, PhD

  Hospital Infantil Universitario Niño Jesús (HIUNJ)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2019
• First Posted: January 31, 2019
• Study Start: April 15, 2019
• Primary Completion: October 1, 2021
• Study Completion: October 1, 2021
• Last Updated: December 7, 2021

Record last verified: 2021-11

Locations

ES (1)