Fanconi Anemia Complementation Group APhase 1NCT03814408
A Clinical Trial to Evaluate the Safety of RP-L102 in Pediatric Subjects With Fanconi Anemia Subtype A
A Phase 1 study testing RP-L102 in people with Fanconi Anemia Complementation Group A, run by Rocket Pharmaceuticals Inc. at 1 site in United States.
Trial summary
The objective of this study is to assess the therapeutic safety and preliminary efficacy of a hematopoietic cell-based gene therapy consisting of autologous CD34+ enriched cells transduced with a lentiviral vector carrying the FANCA gene in subjects with Fanconi anemia subtype A (FA-A). Read more about this study
- Who is it for?
- Ages 1 year to 12 years
- Conditions the study is for
- Fanconi Anemia Complementation Group A
- What is being tested?
- RP-L102
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Jan 2019to Mar 2022
- 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 year to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Fanconi anemia, as diagnosed by chromosomal fragility assay of cultured T-lymphocytes in the presence of DEB or a similar DNA-crosslinking agent.
- Subjects of Fanconi Anemia complementation group A.
- Minimum age: 1 year and a minimum of 8 kg.
- Maximum age: 12 years.
- At least one of the following hematologic parameters below lower limits of normal:
- Hemoglobin
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- Absolute neutrophils
- Platelets
- At least 30 CD34+ cells/μL are determined in one BM aspiration within 3 months prior to initiation of CD34+ cell collection.
- If the number of C34+ cells/ μL in BM is in the range of 10-29, PB parameters should meet two of the three following criteria:
- Hemoglobin: ≥11g/dL
- Neutrophils: ≥900 cells/μL
- Platelets: ≥60,000 cells/μL
- Provide informed consent in accordance with current legislation.
- Women of childbearing age must have a negative urine pregnancy test at the baseline visit and accept the use of an effective contraception method during participation in the trial.
Who cannot join
- Subjects with an available and medically eligible human leukocyte antigen (HLA)-identical sibling donor.
- Evidence of myelodysplastic syndrome or leukemia, or cytogenetic abnormalities predictive of these conditions in BM aspirate analysis. This assessment should be made by valid studies conducted within the 3 months before the subject commences the stem cell mobilization/collection procedures of the clinical trial.
- Subjects with somatic mosaicism associated with stable or improved counts in all PB cell lineages. (If T-lymphocyte chromosomal fragility analysis indicates potential mosaicism, a medically significant decrease in at least one blood lineage over time must be documented to enable eligibility).
- Lansky performance status ≤60%.
- Any concomitant disease or condition that, in the opinion of the Principal Investigator, renders the subject unfit to participate in the study.
- Pre-existing sensory or motor impairment ≥grade 2 according to the NCI CTCAE v5.0 criteria.
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- Pregnant or breastfeeding women.
- Hepatic dysfunction as defined by either:
- Bilirubin >3.0 × upper limit of normal (ULN) or
- Alanine aminotransferase (ALT) > 5.0 × ULN or
- Aspartate aminotransferase (AST) > 5.0 × ULN
- Renal dysfunction requiring either hemodialysis or peritoneal dialysis.
- Pulmonary dysfunction as defined by either:
- Need for supplemental oxygen during the prior 2 weeks in absence of acute infection.
- Oxygen saturation by pulse oximetry <90%.
- Evidence of active metastatic or locoregionally advanced malignancy for which survival is anticipated to be less than 3 years.
- Subject is receiving androgens (i.e. danazol, oxymethalone).
Trial locations and contacts
1 site in 1 country.
United States1 site
Stanford University Institute for Stem Cell Biology and Regenerative Medicine Lucille Packard Children's Hospital, Stanford University
Stanford, California, 94304
About this study
Official title: A Phase I Clinical Trial to Evaluate the Safety of the Infusion of Autologous CD34+ Cells Transduced With a Lentiviral Vector Carrying the FANCA Gene in Pediatric Subjects With Fanconi Anemia Subtype A
The objective of this study is to assess the therapeutic safety and preliminary efficacy of a hematopoietic cell-based gene therapy consisting of autologous CD34+ enriched cells transduced with a lentiviral vector carrying the FANCA gene in subjects with Fanconi anemia subtype A (FA-A).
Read the detailed description
This is a pediatric open-label Phase 1 clinical trial and will include a safety evaluation and preliminary assessment of the efficacy of hematopoietic gene therapy consisting of autologous CD34+ enriched cells transduced with a lentiviral vector carrying the FANCA gene in subjects with FA-A. CD34+ cells will be transduced ex vivo with the therapeutic lentiviral vector and infused following transduction, without any prior conditioning. After transduction, product quality control evaluations will be carried out in aliquots of the transduced population. Investigational product will be infused via intravenous infusion with no upper or lower limit; a dose of ≥5 x 105 CD34+ cells/kg body weight will be considered optimal.
The active agent is a self-inactivating lentiviral vector carrying the therapeutic FANCA gene and the therapeutic product is subject's autologous HSCs that have been transduced with the lentiviral vector. The vector contains the functional FANCA gene.
- Conditions
- Fanconi Anemia Complementation Group A
- Being tested
- RP-L102
- Keywords
- FANCA, FA-A, Fanconi Anemia Subtype A
- Medical subject headings
- Fanconi Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RP-L102Biological
CD34+ enriched cells from subjects with Fanconi anemia subtype A transduced ex vivo with lentiviral vector carrying the FANCA gene, PGK-FANCA-WPRE
| Study group | Role | What they receive |
|---|---|---|
| RP-L102 | Experimental | RP-L102 is a self-inactivating lentiviral vector carrying the therapeutic FANCA gene Receives: Biological: RP-L102 |
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 CTCAE v.5.0
Evaluation of safety associated with treatment with RP-L102
Measured: 3 years
Secondary outcomes (4)
Phenotypic correction of T-lymphocytes in peripheral blood after infusion of RP-L102
Assessment of the percentage of peripheral blood T-cells with DEB-induced chromosomal aberrations that decreases from over or equal to 50% at 0-2 months post-infusion to less than 50% during months 6-36 post-infusion (confirmed in at least 2 determinations conducted in each interval).
Measured: 3 years
Phenotypic correction of hematopoietic cells in bone marrow after infusion of RP-L102
During months 6-36 post-infusion, the survival of bone marrow colony forming units to 10nM MMC increases to over or equal to 10% than values determined at 0-2 months post-infusion. (1 determination is considered valid).
Measured: 3 years
Engraftment of gene-corrected hematopoietic cells after infusion of RP-L102
The level of gene marking of the FANCA-LV provirus in total peripheral blood cells is at least 0.1 vector copy number/nucleated cell during months 6-36 post-infusion. (This should be confirmed in at least 2 determinations conducted at different intervals). An increase in the vector copy number/peripheral blood cell is observed from 0-2 months post-infusion to the 3rd year post-infusion. (This should be confirmed in at least 2 determinations conducted in each interval periods).
Measured: 3 years
Prevention or rescue of bone marrow failure after infusion of RP-L102
Assessment of the need for treatment of bone marrow failure 6-36 months post-infusion. During the 3rd year post-infusion, peripheral blood parameters: hemoglobin levels, neutrophils, and platelets will be assessed and considered stable if they remain at over or equal to 80% of values determined at pre-treatment evaluation visit or immediately prior to mobilization before the administration of granulocyte-colony stimulating factor.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2019
- Study start11 Jan 2019
- Primary completionDec 2020 (estimated)
- Study completionMar 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Fanconi Anemia Complementation Group AStudies 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
- 2 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Rocket Pharmaceuticals Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Agnieszka Czechowicz, MD, Principal investigator, Stanford University, Stem Cell Transplantation and Regenerative Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03814408
- Sponsor's protocol ID
- RP-L102-0418
- Status last verified
- Nov 2020
- First submitted
- 14 Jan 2019
- Last updated
- 24 Nov 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Clinical Trial to Evaluate the Safety of the Infusion of Autologous CD34+ Cells Transduced With a Lentiviral Vector Carrying the FANCA Gene in Pediatric Subjects With Fanconi Anemia Subtype A
- ClinicalTrials.gov ID
- NCT03814408
- Acronym / sponsor ID
- RP-L102-0418
- Conditions
- Fanconi Anemia Complementation Group A
- Keywords
- FANCA, FA-A, Fanconi Anemia Subtype A
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 2 participants (estimated)
- Lead sponsor
- Rocket Pharmaceuticals Inc.Industry (pharma, biotech, devices)
- Study start
- 11 Jan 2019 (actual)
- Primary completion
- Dec 2020 (estimated)
- Study completion
- Mar 2022 (estimated)
- First posted
- 24 Jan 2019 (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 objective of this study is to assess the therapeutic safety and preliminary efficacy of a hematopoietic cell-based gene therapy consisting of autologous CD34+ enriched cells transduced with a lentiviral vector carrying the FANCA gene in subjects with Fanconi anemia subtype A (FA-A).
Detailed description
This is a pediatric open-label Phase 1 clinical trial and will include a safety evaluation and preliminary assessment of the efficacy of hematopoietic gene therapy consisting of autologous CD34+ enriched cells transduced with a lentiviral vector carrying the FANCA gene in subjects with FA-A. CD34+ cells will be transduced ex vivo with the therapeutic lentiviral vector and infused following transduction, without any prior conditioning. After transduction, product quality control evaluations will be carried out in aliquots of the transduced population. Investigational product will be infused via intravenous infusion with no upper or lower limit; a dose of ≥5 x 105 CD34+ cells/kg body weight will be considered optimal.
The active agent is a self-inactivating lentiviral vector carrying the therapeutic FANCA gene and the therapeutic product is subject's autologous HSCs that have been transduced with the lentiviral vector. The vector contains the functional FANCA gene.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RP-L102 | Experimental | Biological: RP-L102RP-L102 is a self-inactivating lentiviral vector carrying the therapeutic FANCA gene |
Who may qualify
- Ages
- 1 year to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (15 listed)
- Fanconi anemia, as diagnosed by chromosomal fragility assay of cultured T-lymphocytes in the presence of DEB or a similar DNA-crosslinking agent.
- Subjects of Fanconi Anemia complementation group A.
- Minimum age: 1 year and a minimum of 8 kg.
- Maximum age: 12 years.
- At least one of the following hematologic parameters below lower limits of normal:
Key exclusion criteria (17 listed)
- Subjects with an available and medically eligible human leukocyte antigen (HLA)-identical sibling donor.
- Evidence of myelodysplastic syndrome or leukemia, or cytogenetic abnormalities predictive of these conditions in BM aspirate analysis. This assessment should be made by valid studies conducted within the 3 months before the subject commences the stem cell mobilization/collection procedures of the clinical trial.
- Subjects with somatic mosaicism associated with stable or improved counts in all PB cell lineages. (If T-lymphocyte chromosomal fragility analysis indicates potential mosaicism, a medically significant decrease in at least one blood lineage over time must be documented to enable eligibility).
- Lansky performance status ≤60%.
- Any concomitant disease or condition that, in the opinion of the Principal Investigator, renders the subject unfit to participate in the study.
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-L102CD34+ enriched cells from subjects with Fanconi anemia subtype A transduced ex vivo with lentiviral vector carrying the FANCA gene, PGK-FANCA-WPRE | Biological | RP-L102 |
Primary outcome
Number of participants with treatment-related adverse events as assessed by CTCAE v.5.0
Time frame: 3 years
Evaluation of safety associated with treatment with RP-L102
4 secondary outcomes
Phenotypic correction of T-lymphocytes in peripheral blood after infusion of RP-L102
Time frame: 3 years
Phenotypic correction of hematopoietic cells in bone marrow after infusion of RP-L102
Time frame: 3 years
Engraftment of gene-corrected hematopoietic cells after infusion of RP-L102
Time frame: 3 years
Prevention or rescue of bone marrow failure after infusion of RP-L102
Time frame: 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Nov 2020.
- Individual participant dataSharing planned: No
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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.
Agnieszka Czechowicz, MD principal investigator
Stanford University, Stem Cell Transplantation and Regenerative Medicine
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-L102 in people with Fanconi Anemia Complementation Group A, 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 15 inclusion and 17 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: status not confirmed, as of the sponsor's last update on 24 Nov 2020. 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?
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 CTCAE v.5.0 (time frame: 3 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 24 Nov 2020.