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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT04525352
Recruitment Status : Terminated (Study discontinued due to feasibility.)
First Posted : August 25, 2020
Last Update Posted : July 13, 2022
California Institute for Regenerative Medicine (CIRM)
Information provided by (Responsible Party):
Rocket Pharmaceuticals Inc.

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.

Condition or disease Intervention/treatment Phase
Infantile Malignant Osteopetrosis Biological: RP-L401 Phase 1

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).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : November 19, 2020
Actual Primary Completion Date : May 21, 2021
Actual Study Completion Date : May 21, 2021

Resource links provided by the National Library of Medicine

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

Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. Assessment of ophthalmology status after infusion of RP-L401 [ Time Frame: 2 years ]
    Evaluation of optical abnormalities via visual assessments of the eye

  7. Assessment of hepatosplenomegaly after infusion of RP-L401 [ Time Frame: 2 years ]
    Evaluation of hepatosplenomegaly improvement via abdominal ultrasound

  8. 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

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Ages Eligible for Study:   1 Month and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04525352

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United States, California
University of California, Los Angeles
Los Angeles, California, United States, 90095
Sponsors and Collaborators
Rocket Pharmaceuticals Inc.
California Institute for Regenerative Medicine (CIRM)
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Principal Investigator: Donald B Kohn, MD University of California, Los Angeles
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Responsible Party: Rocket Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT04525352    
Other Study ID Numbers: RP-L401-0120
First Posted: August 25, 2020    Key Record Dates
Last Update Posted: July 13, 2022
Last Verified: July 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Rocket Pharmaceuticals Inc.:
Impaired bone resorption
Deficient osteoclast development
Autosomal Recessive Disorder
Musculoskeletal Diseases
Bone Diseases
Bone marrow failure
Additional relevant MeSH terms:
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Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases