Rocket Pharmaceuticals: Gene Therapy RP-L401-0120 For Infantile Malignant Osteopetrosis

Highlights of RP-L401-120 Clinical Development 

- Infantile Malignant Osteopetrosis (IMO) is a rare, severe autosomal recessive disorder caused by mutations in the TCIRG1 gene
- RP-L401 is a gene therapy product containing autologous genetically modified CD34+ hematopoietic cells transduced with a lentiviral vector carrying the TCIRG1 transgene
- Proof of concept showed in vitro restoration of osteoclast resorptive function and in vivo correction in a murine model
- Rocket’s Investigational New Drug Application (IND) for RP-L401 was accepted by the U.S. Food and Drug Administration (FDA) in June of 2020 

About Infantile Malignant Osteopetrosis
Infantile Malignant Osteopetrosis (IMO) is a rare, severe autosomal recessive disorder caused by mutations in the TCIRG1 gene, which is critical for the process of bone resorption. Mutations in TCIRG1 interfere with the function of osteoclasts, cells which are essential for normal bone remodeling and growth, leading to skeletal malformations, including fractures and cranial deformities which cause neurologic abnormalities including vision and hearing loss. Patients often have endocrine abnormalities and progressive, frequently fatal bone marrow failure. As a result, death is common within the first decade of life. IMO has an estimated incidence of 1 in 200,000. The only treatment option currently available for IMO is an allogenic bone marrow transplant (HSCT), which allows for the restoration of bone resorption by donor-derived osteoclasts which originate from hematopoietic cells. Long-term survival rates are lower in IMO than those associated with HSCT for many other non-malignant hematologic disorders; severe HSCT-related complications are frequent. There is an urgent need for additional treatment options.

Treatment Platform: 
RP-L401 is a gene therapy product containing autologous genetically modified CD34+ hematopoietic cells transduced with a lentiviral vector carrying the TCIRG1 transgene
 Ex-vivo Gene Therapy Cossu et al. 2017 Lancet

Regulatory Status: Rare Pediatric Disease, Orphan Drug and Fast Track designations in the US.  Rocket’s Investigational New Drug Application (IND) for RP-L401 was accepted by the U.S. Food and Drug Administration (FDA) in June of 2020

Phase I Study Title: 
A Trial to Evaluate Safety and Efficacy of RP-L401-0120 in Subjects With Infantile Malignant Osteopetrosis

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 (LV) EFS-TCIRGI-WPRE 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 Design
Study Type:                     Interventional (Clinical Trial)
Estimated Enrollment:    2 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

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

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 [ Time Frame: 2 years ], Evaluation of safety associated with treatment with RP-L401

Secondary Outcome Measures
  • 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

Source
https://ir.rocketpharma.com/static-files/8ccee97a-9174-43c3-aa80-54f69cb5d46d
clinicaltrial.gov

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