NCT04525352TerminatedPhase 1
A Phase I Clinical Trial for Gene Therapy in Infantile Malignant Osteopetrosis (IMO) to Evaluate the Safety and Preliminary Efficacy of Autologous CD34+ Enriched Cells Transduced With a LV Vector Encoding the TCIRG1 Gene
Rocket Pharmaceuticals Inc.2 sites in 1 country1 target enrollmentStarted: November 19, 2020Last updated:
Conditions
Trial Snapshot
- Phase
- Phase 1
- Status
- Terminated
- Sponsor
- Rocket Pharmaceuticals Inc.
- Enrollment
- 1
- Locations
- 2
- Primary Endpoint
- Number of participants with treatment-related adverse events as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Study Overview
Brief Summary
The primary objective of this Phase 1 study is to evaluate the therapeutic safety and feasibility of the investigational product (IP), RP-L401.
Detailed Description
This is a non-randomized Phase 1 study to evaluate the preliminary safety and efficacy of hematopoietic gene therapy consisting of autologous CD34+ enriched hematopoietic cells transduced with the lentiviral vector (LV) carrying the human TCIRG1 transgene (RP-L401) in pediatric patients with IMO. Following myeloablative conditioning patients will receive an infusion of the genetically modified hematopoietic stem and progenitor cells (HSPCs).
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 1 Month to — (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •A confirmed diagnosis of IMO with documented TCIRG1 mutation.
- •Age at least 1 month with minimum weight of 4 kg
- •Absence of debilitating hydrocephalus (defined as hydrocephalus at NCI CTCAE v5.0 Grade 3 or higher persisting despite shunt or similar procedural intervention).
- •Lansky Play Scale of at least 60%
- •Preserved hepatic function (AST/ALT ≤3.0 ULN; bilirubin ≤1.5 ULN; to minimize potential for excessive toxicity from busulfan conditioning)
- •No concomitant medical or other conditions that would represent a contraindication to autologous hematopoietic stem cell transplant.
- •Absolute neutrophil count of ≥500/mm3 and platelet count of ≥25,000/mm3
- •No prior allogeneic or other hematopoietic stem cell transplant.
- •Availability of a non-autologous rescue (back-up) hematopoietic stem cell donor/source
Exclusion Criteria
- •Availability of medically-feasible HLA-matched sibling donor for allogeneic HSCT.
- •Any medical or other contraindication for either apheresis or autologous transplant as determined by the Investigator.
- •Participation in another clinical trial with an investigational drug within 14 days before the informed consent signature. Participation in observational studies is allowed.
- •Active hematologic or solid organ malignancy, not including non-melanoma skin cancer or another carcinoma in situ.
- •Uncontrolled seizure disorder.
- •Renal dysfunction as defined by a glomerular filtration rate <30 mL/min/1.73m2 or dialysis dependence.
- •Serious infections with persistent bloodstream pathogens at time of trial entry
- •Pulmonary dysfunction as defined by either:
- •Need for supplemental oxygen during the prior 2 weeks (in absence of acute infection) or
- •Oxygen saturation (by pulse oximetry) <90% resulting from pulmonary conditions (intermittent hypoxia secondary to IMO-related choanal atresia will not be considered exclusionary)
Outcomes
Primary Outcomes
Number of participants with treatment-related adverse events as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Time Frame: 2 years
Evaluation of safety associated with treatment with RP-L401
Secondary Outcomes
- Assessment of blood counts after infusion of RP-L401(2 years)
- Assessment of hepatosplenomegaly after infusion of RP-L401(2 years)
- Assessment of head, mouth and gum abnormalities(2 years)
- Assessment of vector copy number (VCN) after infusion of RP-L401(2 years)
- Assessment of endocrine and metabolic status after infusion of RP-L401(2 years)
- Assessment of bone abnormalities after infusion of RP-L401(2 years)
- Assessment of auditory status after infusion of RP-L401(2 years)
- Assessment of ophthalmology status after infusion of RP-L401(2 years)
Investigators
Study Sites (2)
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