Back to resultsA Trial to Evaluate Safety and Efficacy of RP-L401-0120 in Subjects With Infantile Malignant Osteopetrosis
Primary Purpose
Infantile Malignant Osteopetrosis
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
RP-L401
Sponsored by
About this trial
This is an interventional treatment trial for Infantile Malignant Osteopetrosis focused on measuring Impaired bone resorption, Deficient osteoclast development, Autosomal Recessive Disorder, Musculoskeletal Diseases, Bone Diseases, Hypocalcemia, Bone marrow failure
Eligibility Criteria
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)
Sites / Locations
- University of California, Los Angeles
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Experimental - RP-L401
Arm Description
RP-L401 is a gene therapy product containing autologous genetically modified CD34+ hematopoietic cells transduced with lentiviral vector carrying the TCIRG1 transgene
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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
Assessment of endocrine and metabolic status after infusion of RP-L401
Evaluation of normalization of serum calcium levels via a blood assessment
Assessment of blood counts after infusion of RP-L401
Evaluation of the stabilization or improvement in blood counts as assessed by NCI CTACE
Assessment of bone abnormalities after infusion of RP-L401
Evaluation of the qualitative improvement in bone formation via x-ray studies
Assessment of auditory status after infusion of RP-L401
Evaluation of the stabilization or improvement in hearing loss via auditory tests
Assessment of ophthalmology status after infusion of RP-L401
Evaluation of optical abnormalities via visual assessments of the eye
Assessment of hepatosplenomegaly after infusion of RP-L401
Evaluation of hepatosplenomegaly improvement via abdominal ultrasound
Assessment of head, mouth and gum abnormalities
Photographic documentation of head, mouth and gums to assess disease stabilization, progression or improvement
Full Information
NCT ID
NCT04525352
First Posted
August 11, 2020
Last Updated
July 11, 2022
Sponsor
Rocket Pharmaceuticals Inc.
Collaborators
California Institute for Regenerative Medicine (CIRM)
1. Study Identification
Unique Protocol Identification Number
NCT04525352
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Terminated
Why Stopped
Study discontinued due to feasibility.
Study Start Date
November 19, 2020 (Actual)
Primary Completion Date
May 21, 2021 (Actual)
Study Completion Date
May 21, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Rocket Pharmaceuticals Inc.
Collaborators
California Institute for Regenerative Medicine (CIRM)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infantile Malignant Osteopetrosis
Keywords
Impaired bone resorption, Deficient osteoclast development, Autosomal Recessive Disorder, Musculoskeletal Diseases, Bone Diseases, Hypocalcemia, Bone marrow failure
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
1 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Experimental - RP-L401
Arm Type
Experimental
Arm Description
RP-L401 is a gene therapy product containing autologous genetically modified CD34+ hematopoietic cells transduced with lentiviral vector carrying the TCIRG1 transgene
Intervention Type
Biological
Intervention Name(s)
RP-L401
Intervention Description
CD34+ enriched hematopoietic stem cells from pediatric subjects with infantile malignant osteopetrosis transduced ex vivo with lentiviral vector carrying the TCIRG1 transgene
Primary Outcome Measure Information:
Title
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
Description
Evaluation of safety associated with treatment with RP-L401
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Assessment of vector copy number (VCN) after infusion of RP-L401
Description
Evaluation of the presence of gene-modified blood and bone marrow cells post infusion via blood and bone marrow assessments
Time Frame
2 years
Title
Assessment of endocrine and metabolic status after infusion of RP-L401
Description
Evaluation of normalization of serum calcium levels via a blood assessment
Time Frame
2 years
Title
Assessment of blood counts after infusion of RP-L401
Description
Evaluation of the stabilization or improvement in blood counts as assessed by NCI CTACE
Time Frame
2 years
Title
Assessment of bone abnormalities after infusion of RP-L401
Description
Evaluation of the qualitative improvement in bone formation via x-ray studies
Time Frame
2 years
Title
Assessment of auditory status after infusion of RP-L401
Description
Evaluation of the stabilization or improvement in hearing loss via auditory tests
Time Frame
2 years
Title
Assessment of ophthalmology status after infusion of RP-L401
Description
Evaluation of optical abnormalities via visual assessments of the eye
Time Frame
2 years
Title
Assessment of hepatosplenomegaly after infusion of RP-L401
Description
Evaluation of hepatosplenomegaly improvement via abdominal ultrasound
Time Frame
2 years
Title
Assessment of head, mouth and gum abnormalities
Description
Photographic documentation of head, mouth and gums to assess disease stabilization, progression or improvement
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Month
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Donald B Kohn, MD
Organizational Affiliation
University of California, Los Angeles
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California, Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Trial to Evaluate Safety and Efficacy of RP-L401-0120 in Subjects With Infantile Malignant Osteopetrosis
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