CClinicalTrials.gg
Sign In
TerminatedNCT04525352Updated Jul 13, 2022

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

A Phase 1 interventional study of RP-L401 in Infantile Malignant Osteopetrosis, sponsored by Rocket Pharmaceuticals Inc.. Terminated at 1 site in United States. Open to participants aged 1 Month and older. Per ClinicalTrials.gov, last updated 2022-07-13.

Sponsored by Rocket Pharmaceuticals Inc. · Phase 1, Interventional, and Treatment

Why this study was terminated
Study discontinued due to feasibility.
Phase
Phase 1
Study type
Interventional
Enrollment
1
Allocation
Not applicable
Ages
1 Month and older
Sex
All
01

Study summary

The primary objective of this Phase 1 study is to evaluate the therapeutic safety and feasibility of the investigational product (IP), RP-L401.

Read the 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).

02

Conditions studied

  • Infantile Malignant Osteopetrosis

Browse trials for

Keywords

  • Impaired bone resorption
  • Deficient osteoclast development
  • Autosomal Recessive Disorder
  • Musculoskeletal Diseases
  • Bone Diseases
  • Hypocalcemia
  • Bone marrow failure
03

Who can participate

Ages eligible
1 Month and older
Sexes eligible
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

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)
04

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
1 participant (actual)

Study arms

  • 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

Interventions

  • BiologicalRP-L401

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

05

What researchers measure

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

    Time frame: 2 years

Secondary outcomes

  1. 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

    Time frame: 2 years

  2. Assessment of endocrine and metabolic status after infusion of RP-L401

    Evaluation of normalization of serum calcium levels via a blood assessment

    Time frame: 2 years

  3. Assessment of blood counts after infusion of RP-L401

    Evaluation of the stabilization or improvement in blood counts as assessed by NCI CTACE

    Time frame: 2 years

  4. Assessment of bone abnormalities after infusion of RP-L401

    Evaluation of the qualitative improvement in bone formation via x-ray studies

    Time frame: 2 years

  5. Assessment of auditory status after infusion of RP-L401

    Evaluation of the stabilization or improvement in hearing loss via auditory tests

    Time frame: 2 years

  6. Assessment of ophthalmology status after infusion of RP-L401

    Evaluation of optical abnormalities via visual assessments of the eye

    Time frame: 2 years

  7. Assessment of hepatosplenomegaly after infusion of RP-L401

    Evaluation of hepatosplenomegaly improvement via abdominal ultrasound

    Time frame: 2 years

  8. Assessment of head, mouth and gum abnormalities

    Photographic documentation of head, mouth and gums to assess disease stabilization, progression or improvement

    Time frame: 2 years

06

Study locations

1 site
  • University of California, Los Angeles
    Los Angeles, California 90095, United States
07

Registry details

Key details

Study ID
NCT04525352
Lead sponsor
Rocket Pharmaceuticals Inc.
Collaborators
California Institute for Regenerative Medicine (CIRM)
Responsible party
Sponsor
First posted
Aug 25, 2020
Start date
Nov 19, 2020
Primary completion
May 21, 2021
Completion
May 21, 2021
Last update
Jul 13, 2022

Study contacts

Donald B Kohn, MD
principal investigator · University of California, Los Angeles

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is terminated, as verified in Jul 2022. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Osteopetrosis→

Other studies from this sponsor

Rocket Pharmaceuticals Inc.

Start the discussion