Infantile Malignant OsteopetrosisPhase 1NCT04525352
A Trial to Evaluate Safety and Efficacy of RP-L401-0120 in Subjects With Infantile Malignant Osteopetrosis
A Phase 1 study testing RP-L401 in people with Infantile Malignant Osteopetrosis, run by Rocket Pharmaceuticals Inc. at 1 site in United States.
Trial 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 more about this study
- Who is it for?
- Ages 1 month and older
- Conditions the study is for
- Infantile Malignant Osteopetrosis
- What is being tested?
- RP-L401
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Nov 2020to 21 May 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 month and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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.
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- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, Los Angeles
Los Angeles, California, 90095
About this study
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
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).
- Conditions
- Infantile Malignant Osteopetrosis
- Being tested
- RP-L401
- Keywords
- Impaired bone resorption, Deficient osteoclast development, Autosomal Recessive Disorder, Musculoskeletal Diseases, Bone Diseases, Hypocalcemia, Bone marrow failure
- Medical subject headings
- Musculoskeletal Diseases, Bone Diseases, Hypocalcemia, Bone Marrow Failure Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RP-L401Biological
CD34+ enriched hematopoietic stem cells from pediatric subjects with infantile malignant osteopetrosis transduced ex vivo with lentiviral vector carrying the TCIRG1 transgene
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Biological: RP-L401 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 2 years
Secondary outcomes (8)
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
Measured: 2 years
Assessment of endocrine and metabolic status after infusion of RP-L401
Evaluation of normalization of serum calcium levels via a blood assessment
Measured: 2 years
Assessment of blood counts after infusion of RP-L401
Evaluation of the stabilization or improvement in blood counts as assessed by NCI CTACE
Measured: 2 years
Assessment of bone abnormalities after infusion of RP-L401
Evaluation of the qualitative improvement in bone formation via x-ray studies
Measured: 2 years
Assessment of auditory status after infusion of RP-L401
Evaluation of the stabilization or improvement in hearing loss via auditory tests
Measured: 2 years
Assessment of ophthalmology status after infusion of RP-L401
Evaluation of optical abnormalities via visual assessments of the eye
Measured: 2 years
Assessment of hepatosplenomegaly after infusion of RP-L401
Evaluation of hepatosplenomegaly improvement via abdominal ultrasound
Measured: 2 years
Assessment of head, mouth and gum abnormalities
Photographic documentation of head, mouth and gums to assess disease stabilization, progression or improvement
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2020
- Study start19 Nov 2020
- Primary completion21 May 2021
- Study completion21 May 2021
Why it stopped: Study discontinued due to feasibility.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Infantile Malignant OsteopetrosisStudies of the same condition, open and under way.
- More trials run by Rocket Pharmaceuticals Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rocket Pharmaceuticals Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- California Institute for Regenerative Medicine (CIRM)
- Responsible party
- Sponsor
- Investigators
- Donald B Kohn, MD, Principal investigator, University of California, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04525352
- Sponsor's protocol ID
- RP-L401-0120
- Status last verified
- Jul 2022
- First submitted
- 11 Aug 2020
- Last updated
- 13 Jul 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04525352
- Acronym / sponsor ID
- RP-L401-0120
- Conditions
- Infantile Malignant Osteopetrosis
- Keywords
- Impaired bone resorption, Deficient osteoclast development, Autosomal Recessive Disorder, Musculoskeletal Diseases, Bone Diseases, Hypocalcemia, Bone marrow failure
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study discontinued due to feasibility.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Rocket Pharmaceuticals Inc.Industry (pharma, biotech, devices)
- Collaborators
- California Institute for Regenerative Medicine (CIRM)
- Study start
- 19 Nov 2020 (actual)
- Primary completion
- 21 May 2021 (actual)
- Study completion
- 21 May 2021 (actual)
- First posted
- 25 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental - RP-L401 | Experimental | Biological: RP-L401RP-L401 is a gene therapy product containing autologous genetically modified CD34+ hematopoietic cells transduced with lentiviral vector carrying the TCIRG1 transgene |
Who may qualify
- Ages
- 1 month and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- 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)
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RP-L401CD34+ enriched hematopoietic stem cells from pediatric subjects with infantile malignant osteopetrosis transduced ex vivo with lentiviral vector carrying the TCIRG1 transgene | Biological | Experimental - RP-L401 |
Primary outcome
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
8 secondary outcomes
Assessment of vector copy number (VCN) after infusion of RP-L401
Time frame: 2 years
Assessment of endocrine and metabolic status after infusion of RP-L401
Time frame: 2 years
Assessment of blood counts after infusion of RP-L401
Time frame: 2 years
Assessment of bone abnormalities after infusion of RP-L401
Time frame: 2 years
Assessment of auditory status after infusion of RP-L401
Time frame: 2 years
Assessment of ophthalmology status after infusion of RP-L401
Time frame: 2 years
Assessment of hepatosplenomegaly after infusion of RP-L401
Time frame: 2 years
Assessment of head, mouth and gum abnormalities
Time frame: 2 years
Results and safety
The study was stopped early (reason given: Study discontinued due to feasibility.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Donald B Kohn, MD principal investigator
University of California, Los Angeles
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing RP-L401 in people with Infantile Malignant Osteopetrosis, run by Rocket Pharmaceuticals Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Study discontinued due to feasibility.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jul 2022.