Overview
Sponsor-declared trial summary
Phase
Phase I and Phase II (Integrated) - Other
Status
Ongoing, recruiting
Participants planned
9
Countries
1
Sites
1
Fanconi anemia (subtype A)
• To assess survival in subjects treated in the parent study (FANCOLEN-1) • To evaluate long term (LT) safety following infusion of hematopoietic cells transduced with the therapeutic lentiviral LV vector. • To determine long term (LT) persistence of the therapeutic LV (provirus) in hematopoietic cells in the bone ma…
Key facts
- Sponsor
- Rocket Pharmaceuticals Inc.
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
- Trial duration
- 28 May 2020 → ongoing
- Decision date (initial)
- 2024-08-29
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- Yes
- Funding sources
- Rocket Pharmaceuticals, Inc
External identifiers
- EU CT number
- 2024-511523-33-00
- EudraCT number
- 2019-004722-19
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy, Efficacy, Safety
• To assess survival in subjects treated in the parent study (FANCOLEN-1)
• To evaluate long term (LT) safety following infusion of hematopoietic cells transduced
with the therapeutic lentiviral LV vector.
• To determine long term (LT) persistence of the therapeutic LV (provirus) in
hematopoietic cells in the bone marrow (BM) & blood, & evaluate potential
correlations between provirus/transgene persistence & hematologic
stability
• To determine long term (LT) clonality patterns beyond the 3-year follow-up stipulated
in parent study.
• To evaluate, when relevant , replication competent lentivirus (RCL) in serum and peripheral blood (PB) cells
• To determine long-term (LT) stability & normalization of blood counts in subjects after RP-L102
infusion
• To determine the phenotypic correction of BM and PB cells in in long-term follow-up after gene therapy.
• To enable preliminary assessment of the incidence of hematologic malignancies and solid organ tumors.
Secondary objectives 1
- Not Applicable
Conditions and MedDRA coding
Fanconi anemia (subtype A)
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | LLT | 10055206 | Fanconi's anemia | 10010331 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | LT safety/efficacy following infusion of hematopoietic cells transduced with the therapeutic LV Following the end of participation in the FANCOLEN-I Phase 1/2 study protocol (post-RP-L102
infusion), patients are to be offered enrollment in the long-term follow-up protocol, which will
involve assessments of:
• General health status including assessment for BMF, malignancy development, and new
or exacerbation of pre-existing neurological and rheumatologic or other autoimmune
disorders;
• Patient reported outcomes (PRO)/quality of life (QOL) assessments; and
• Blood laboratory evaluations including blood counts, peripheral blood mononuclear (also
referred to as nucleated) cell VCN, including assessment within specific lineages,
resistance of peripheral blood cells to DNA damaging agents (mitomycin-C [MMC] and/or
diepoxybutane [DEB]), integration site analysis, and RCL (when relevant).
Any new hematologic disorders also will be documented.
Results of bone marrow assessments will also be requested from health care providers, including
samples (when feasible) for evaluation of VCN and MMC-resistance in BM cells. If a patient
develops hematologic malignancy, a blood sample will be obtained to enable determination of
whether the malignant clone developed from a gene-corrected lineage or an uncorrected FA
hematopoietic population by means of PCR for the transgene within the malignant population.
Subjects will be followed for up to 15 years post-RP-L102 infusion in the parent study until
withdrawal of consent, lost to follow-up, or death, whichever occurs first. Annual visits to the
study center will be required for up to 5 years post-RP-L102 infusion, with every 6-month visits
encouraged when feasible and every 3-4 month visits permitted when warranted in the opinion of
the investigator and feasible for patients/families.
In subsequent years, yearly follow-up by means of telephone contact, questionnaire, retrieval of
health records, and procurement of blood and bone marrow specimens from local healthcare
providers will be permitted to facilitate evaluation. Visits to the study center are encouraged
whenever feasible.
Blood samples will be archived and tested when clinically or scientifically indicated, as in the
event of development of a second malignancy.
Safety assessments will include blood-based evaluation of integration site analysis in peripheral
blood mononuclear cells (including lineage-specific subsets as determined by flow cytometry),
assessment of RCL (serum and blood cells) when relevant, and detailed history regarding AEs,
including hospitalizations, administration of medications or therapies for bone marrow failure, and
development of hematologic and non-hematologic malignancies. Importantly, in settings of
hematologic malignancy development, a blood sample will be obtained to enable determination of
whether the malignant clone developed from a gene-corrected lineage or an uncorrected FA
hematopoietic population by means of PCR for the transgene within the malignant population.
Efficacy assessments include blood-based evaluation of peripheral blood counts, and ongoing
assessment of phenotypic correction via peripheral blood T-lymphocyte DEB chromosomal
fragility assay. Bone marrow assessments should include evaluations of MMC resistance of colony
forming units (CFUs) in addition to histology (morphology), cytogenetics and other assays (for
example flow cytometry). VCN should also be performed on bone marrow cells including subsets
(CD34+, other lineage-specific markers) when feasible.
|
Not Applicable | None |
Regulatory references
- Scientific advice from competent authorities
- European Medicines Agency
- Plan to share IPD
- No
| EU CT number | Title | Sponsor |
|---|---|---|
| 2011-006100-12 | Clinical Trial Phase I / II to evaluate the safety and efficacy of the infusion of autologous CD34+ cells transduced with a lentiviral vector carrying the FANCA gene (orphan drug) for patients with Fanconi Anemia Subtype A., Ensayo clínico Fase I/II para evaluar la seguridad y eficacia de la infusión de células CD34+ autólogas transducidas con un vector lentiviral portador del gen FANCA (medicamento huérfano) para pacientes con Anemia de Fanconi del Subtipo A., Ensayo clínico Fase I/II para evaluar la seguridad y eficacia de la infusión de células CD34+ autólogas transducidas con un vector lentiviral portador del gen FANCA (medicamento huérfano) para pacientes con Anemia de Fanconi del Subtipo A. |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 1
- Subjects must meet all the following criteria to be included in the study: 1. Was enrolled in the clinical phase 1/2 study FANCOLEN-I. 2. Received infusion of autologous CD34+ enriched gene corrected hematopoietic cells in clinical phase 1/2 study FANCOLEN-I. 3. Is willing and able to adhere to the study visit schedule and other protocol requirements. 4. Provided written informed consent and, as applicable, assent to participate in the current study in accordance with current regulatory requirements. Patients who have undergone allogeneic HSCT (either because of bone marrow failure or leukemia/MDS) will also be followed in this protocol. Evaluations for VCN in HSCT recipients will not be performed if 3 prior assessments did not indicate presence of provirus (transgene) in any evaluated cell population.
Exclusion criteria 1
- There are no criteria for exclusion in this study.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Safety Assessments: will include blood-based evaluation of integration site analysis (ISA) in peripheral blood mononuclear cells (including lineage-specific subsets as determined by flow cytometry), assessment of RCL (serum and blood cells) when relevant, and detailed history regarding adverse events including hospitalizations, administration of medications or therapies for bone marrow failure, and development of hematologic and non-hematologic malignancies.
Secondary endpoints 1
- Importantly, in settings of hematologic malignancy development, a blood sample will be obtained to enable determination of whether the malignant clone developed from a gene-corrected lineage or an uncorrected FA hematopoietic population by means of PCR for the transgene within the malignant population. Efficacy Assessments: will include blood-based evaluation of peripheral blood counts, and ongoing assessment of phenotypic correction via peripheral blood T-lymphocyte DEB chromosomal fragility
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
PRD7872283 · Product
- Active substance
- Autologous CD34ENRICHED Cells From Patients with Fanconi Anemia Subtype a Transduced Ex Vivo with Lentiviral Vector Carrying the Fanconi Anemia Complementation Group a Gene
- Pharmaceutical form
- INFUSION
- Route of administration
- INTRAVENOUS USE
- Authorisation status
- Not Authorised
- ATC code
- B05AX — -
- MA holder
- ROCKET PHARMACEUTICALS, INC.
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- EU/3/10/822
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Rocket Pharmaceuticals Inc.
- Sponsor organisation
- Rocket Pharmaceuticals Inc.
- Address
- 9 Cedarbrook Drive
- City
- Cranbury
- Postcode
- 08512-3618
- Country
- United States
Scientific contact point
- Organisation
- Rocket Pharmaceuticals Inc.
- Contact name
- Clinical Trials
Public contact point
- Organisation
- Rocket Pharmaceuticals Inc.
- Contact name
- Clinical Trials
Third parties 5
| Organisation | City, country | Duties |
|---|---|---|
| Hospital De La Santa Creu I Sant Pau ORG-100028622
|
Barcelona, Spain | Other |
| Medizinische Hochschule Hannover ORG-100024473
|
Hanover, Germany | Other |
| Premier Research Group S.L. ORG-100013963
|
Madrid, Spain | On site monitoring, Code 10, Code 11, Code 12, Code 2, Code 5, Data management, E-data capture, Code 8, Code 9 |
| Precision For Medicine Inc. ORG-100041895
|
Frederick, United States | Other |
| Genezen Laboratories Inc. ORG-100048847
|
Indianapolis, United States | Other, Laboratory analysis |
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Spain | Ongoing, recruiting | 9 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Spain | 2020-05-28 | 2020-06-04 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 7 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_ Protocol 2024-511523-33-00 Redacted | 1.3 |
| Recruitment arrangements (for publication) | K1 Recruitment arrangements | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Adults _Redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Assent 12-17 | 3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Parents Redacted | 5.0 |
| Synopsis of the protocol (for publication) | D1_ Protocol synopsis_ESP_2024-511523-33-00 Redacted | 1.3 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis ENG 2024-511523-33-00_Redacted | 1.3 |
Application history
3 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-08-22 | Spain | Acceptable with conditions 2024-08-29
|
2024-08-29 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2025-05-08 | Spain | Acceptable 2025-06-23
|
2025-06-23 |
| 3 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2026-03-20 | Spain | Acceptable 2025-06-23
|
2026-03-20 |