NCT04525352

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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Nov 2020

Shorter than P25 for phase_1

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 11, 2020

Completed
14 days until next milestone

First Posted

Study publicly available on registry

August 25, 2020

Completed
3 months until next milestone

Study Start

First participant enrolled

November 19, 2020

Completed
6 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 21, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 21, 2021

Completed
Last Updated

July 13, 2022

Status Verified

July 1, 2022

Enrollment Period

6 months

First QC Date

August 11, 2020

Last Update Submit

July 11, 2022

Conditions

Infantile Malignant Osteopetrosis

Keywords

Impaired bone resorptionDeficient osteoclast developmentAutosomal Recessive DisorderMusculoskeletal DiseasesBone DiseasesHypocalcemiaBone marrow failure

Outcome Measures

Primary Outcomes (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

    Evaluation of safety associated with treatment with RP-L401

    2 years

Secondary Outcomes (8)

  • Assessment of vector copy number (VCN) after infusion of RP-L401

    2 years

  • Assessment of endocrine and metabolic status after infusion of RP-L401

    2 years

  • Assessment of blood counts after infusion of RP-L401

    2 years

  • Assessment of bone abnormalities after infusion of RP-L401

    2 years

  • Assessment of auditory status after infusion of RP-L401

    2 years

  • +3 more secondary outcomes

Study Arms (1)

Experimental - RP-L401

EXPERIMENTAL

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

Interventions

RP-L401BIOLOGICAL

CD34+ enriched hematopoietic stem cells from pediatric subjects with infantile malignant osteopetrosis transduced ex vivo with lentiviral vector carrying the TCIRG1 transgene

Experimental - RP-L401

Eligibility Criteria

Age1 Month+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

MeSH Terms

Conditions

Musculoskeletal DiseasesBone DiseasesHypocalcemiaBone Marrow Failure Disorders

Condition Hierarchy (Ancestors)

Calcium Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesWater-Electrolyte ImbalanceBone Marrow DiseasesHematologic DiseasesHemic and Lymphatic Diseases

Study Officials

  • Donald B Kohn, MD

    University of California, Los Angeles

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 11, 2020

First Posted

August 25, 2020

Study Start

November 19, 2020

Primary Completion

May 21, 2021

Study Completion

May 21, 2021

Last Updated

July 13, 2022

Record last verified: 2022-07

Locations

US(1)