A Trial to Evaluate Safety and Efficacy of RP-L401-0120 in Subjects With Infantile Malignant Osteopetrosis

• ClinicalTrials.gov Identifier: NCT04525352
• Recruitment Status: Terminated
• First Posted: August 25, 2020
• Last Update Posted: July 13, 2022
• Sponsor: Rocket Pharmaceuticals Inc.
• Collaborator: California Institute for Regenerative Medicine (CIRM)
• Information provided by (Responsible Party): Rocket Pharmaceuticals Inc.

Tracking Information

• First Submitted Date: August 11, 2020
• First Posted Date: August 25, 2020
• Last Update Posted Date: July 13, 2022
• Actual Study Start Date: November 19, 2020
• Actual Primary Completion Date: May 21, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 20, 2020)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 20, 2020)

• Assessment of vector copy number (VCN) after infusion of RP-L401 [ Time Frame: 2 years ]
  Evaluation of the presence of gene-modified blood and bone marrow cells post infusion via blood and bone marrow assessments
• Assessment of endocrine and metabolic status after infusion of RP-L401 [ Time Frame: 2 years ]
  Evaluation of normalization of serum calcium levels via a blood assessment
• Assessment of blood counts after infusion of RP-L401 [ Time Frame: 2 years ]
  Evaluation of the stabilization or improvement in blood counts as assessed by NCI CTACE
• Assessment of bone abnormalities after infusion of RP-L401 [ Time Frame: 2 years ]
  Evaluation of the qualitative improvement in bone formation via x-ray studies
• Assessment of auditory status after infusion of RP-L401 [ Time Frame: 2 years ]
  Evaluation of the stabilization or improvement in hearing loss via auditory tests
• Assessment of ophthalmology status after infusion of RP-L401 [ Time Frame: 2 years ]
  Evaluation of optical abnormalities via visual assessments of the eye
• Assessment of hepatosplenomegaly after infusion of RP-L401 [ Time Frame: 2 years ]
  Evaluation of hepatosplenomegaly improvement via abdominal ultrasound
• Assessment of head, mouth and gum abnormalities [ Time Frame: 2 years ]
  Photographic documentation of head, mouth and gums to assess disease stabilization, progression or improvement

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Trial to Evaluate Safety and Efficacy of RP-L401-0120 in Subjects With Infantile Malignant Osteopetrosis
• Official Title: 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
• 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 Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Infantile Malignant Osteopetrosis

Intervention

Biological: RP-L401

CD34+ enriched hematopoietic stem cells from pediatric subjects with infantile malignant osteopetrosis transduced ex vivo with lentiviral vector carrying the TCIRG1 transgene

Study Arms

Experimental: Experimental - RP-L401

RP-L401 is a gene therapy product containing autologous genetically modified CD34+ hematopoietic cells transduced with lentiviral vector carrying the TCIRG1 transgene

Intervention: Biological: RP-L401

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: July 11, 2022): 1
• Original Estimated Enrollment (submitted: August 20, 2020): 2
• Actual Study Completion Date: May 21, 2021
• Actual Primary Completion Date: May 21, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. A confirmed diagnosis of IMO with documented TCIRG1 mutation.
2. Age at least 1 month with minimum weight of 4 kg
3. Absence of debilitating hydrocephalus (defined as hydrocephalus at NCI CTCAE v5.0 Grade 3 or higher persisting despite shunt or similar procedural intervention).
4. Lansky Play Scale of at least 60%
5. Preserved hepatic function (AST/ALT ≤3.0 ULN; bilirubin ≤1.5 ULN; to minimize potential for excessive toxicity from busulfan conditioning)
6. No concomitant medical or other conditions that would represent a contraindication to autologous hematopoietic stem cell transplant.
7. Absolute neutrophil count of ≥500/mm3 and platelet count of ≥25,000/mm3
8. No prior allogeneic or other hematopoietic stem cell transplant.
9. Availability of a non-autologous rescue (back-up) hematopoietic stem cell donor/source

Exclusion Criteria:

1. Availability of medically-feasible HLA-matched sibling donor for allogeneic HSCT.
2. Any medical or other contraindication for either apheresis or autologous transplant as determined by the Investigator.
3. Participation in another clinical trial with an investigational drug within 14 days before the informed consent signature. Participation in observational studies is allowed.
4. Active hematologic or solid organ malignancy, not including non-melanoma skin cancer or another carcinoma in situ.
5. Uncontrolled seizure disorder.
6. Renal dysfunction as defined by a glomerular filtration rate <30 mL/min/1.73m2 or dialysis dependence.
7. Serious infections with persistent bloodstream pathogens at time of trial entry

8. 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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Month and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04525352
• Other Study ID Numbers: RP-L401-0120
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Rocket Pharmaceuticals Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Rocket Pharmaceuticals Inc.
• Original Study Sponsor: Same as current
• Collaborators: California Institute for Regenerative Medicine (CIRM)

Investigators

• Principal Investigator: Donald B Kohn, MD; University of California, Los Angeles

• PRS Account: Rocket Pharmaceuticals Inc.
• Verification Date: July 2022