Infantile Malignant Osteopetrosis Clinical Trial
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
| Verified date | July 2022 |
| Source | Rocket Pharmaceuticals Inc. |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
The primary objective of this Phase 1 study is to evaluate the therapeutic safety and feasibility of the investigational product (IP), RP-L401.
| Status | Terminated |
| Enrollment | 1 |
| Est. completion date | May 21, 2021 |
| Est. primary completion date | May 21, 2021 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 1 Month and older |
| Eligibility | 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) |
| Country | Name | City | State |
|---|---|---|---|
| United States | University of California, Los Angeles | Los Angeles | California |
| Lead Sponsor | Collaborator |
|---|---|
| Rocket Pharmaceuticals Inc. | California Institute for Regenerative Medicine (CIRM) |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | 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 | |
| Secondary | Assessment of endocrine and metabolic status after infusion of RP-L401 | Evaluation of normalization of serum calcium levels via a blood assessment | 2 years | |
| Secondary | 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 | |
| Secondary | Assessment of bone abnormalities after infusion of RP-L401 | Evaluation of the qualitative improvement in bone formation via x-ray studies | 2 years | |
| Secondary | Assessment of auditory status after infusion of RP-L401 | Evaluation of the stabilization or improvement in hearing loss via auditory tests | 2 years | |
| Secondary | Assessment of ophthalmology status after infusion of RP-L401 | Evaluation of optical abnormalities via visual assessments of the eye | 2 years | |
| Secondary | Assessment of hepatosplenomegaly after infusion of RP-L401 | Evaluation of hepatosplenomegaly improvement via abdominal ultrasound | 2 years | |
| Secondary | Assessment of head, mouth and gum abnormalities | Photographic documentation of head, mouth and gums to assess disease stabilization, progression or improvement | 2 years |