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

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

The primary objective of this Phase 1 study is to evaluate the therapeutic safety and feasibility of the investigational product (IP), RP-L401.

Study Overview

• Status: Terminated
• Conditions: Infantile Malignant Osteopetrosis
• Intervention / Treatment: Biological: 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
• Enrollment (Actual): 1
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Evaluation of safety associated with treatment with RP-L401	2 years

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Rocket Pharmaceuticals Inc.
• Collaborators: California Institute for Regenerative Medicine (CIRM)
• Investigators: Principal Investigator: Donald B Kohn, MD, University of California, Los Angeles

Study record dates

Study Major Dates

• Study Start (Actual): November 19, 2020
• Primary Completion (Actual): May 21, 2021
• Study Completion (Actual): May 21, 2021

Study Registration Dates

• First Submitted: August 11, 2020
• First Submitted That Met QC Criteria: August 20, 2020
• First Posted (Actual): August 25, 2020

Study Record Updates

• Last Update Posted (Actual): July 13, 2022
• Last Update Submitted That Met QC Criteria: July 11, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Musculoskeletal Diseases; Bone Diseases; Hypocalcemia; Impaired bone resorption; Deficient osteoclast development; Autosomal Recessive Disorder; Bone marrow failure
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Developmental; Osteochondrodysplasias; Osteosclerosis; Osteopetrosis
• Other Study ID Numbers: RP-L401-0120

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No