Long-Term Follow-up: Phase I/II clinical study to evaluate the safety and efficacy of the infusion of RP-L102

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Rocket Pharmaceuticals Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

1 Mar 2023 → ongoing

Decision date (initial)

2022-10-07

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Rocket Pharmaceuticals, Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

• To evaluate long-term safety following infusion of hematopoietic cells transduced with the therapeutic lentiviral vector (LV).
• To determine long-term persistence of the therapeutic LV (provirus) in hematopoietic cells in the bone marrow (BM) and blood, and to evaluate potential correlations between provirus/transgene persistence and hematologic stability (absence of bone marrow failure [BMF] or hematologic malignancy).
• To determine long-term clonality patterns beyond the 3-year follow-up stipulated in the RP-L102 parent studies (RP-L102-0418, RP-L102-0319, RP-L102-0118).
• To evaluate, when relevant, replication-competent lentivirus (RCL) in serum and peripheral blood cells (this will not be considered relevant for subjects in whom no evidence of RCL was identified during the initial year following investigational autologous cell infusion).
• To determine the long-term stability and normalization of blood counts in patients subsequent to infusion of autologous Fanconi Anemia Group A (FANCA)-corrected hematopoietic cells.
• To determine the phenotypic correction of BM and peripheral blood (PB) cells (as evaluated by resistance to DNA-damaging agents) in long-term follow-up after gene therapy.
• To enable preliminary assessment of the incidence of hematologic malignancies (including acute myeloid leukemia [AML]/myelodysplastic syndrome [MDS]) and solid organ tumors (including squamous cell carcinoma of the head and neck); occurrence of these events will be evaluated in the context of the underlying rates of these malignancies in Fanconi anemia (FA) patient populations (both those who have not undergone allogeneic stem cell transplant and FA patients post-hematopoietic stem cell transplantation [HSCT]).

Conditions and MedDRA coding

Fanconi anemia subtype A (FA-A)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-002578-PIP01-19

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Subject was enrolled in one of the RP-L102 parent studies (RP-L102-0418, RP-L102-0319, RP-L102-0118).
2. Subject received an autologous infusion of CD34+ enriched cells transduced ex vivo with LV vector carrying the FANCA gene, PGK-FANCA-WPRE (RP-L102), in the parent study.
3. Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
4. Subject has provided written informed consent and, as applicable, assent to participate in the current study in accordance with current regulatory requirements.

Exclusion criteria 1

1. There are no exclusion criteria in this study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 7

1. To evaluate long-term safety following infusion of hematopoietic cells transduced with the therapeutic LV
2. To determine long-term persistence of the therapeutic LV (provirus) in hematopoietic cells in the bone marrow (BM) and blood, and to evaluate potential correlations between provirus/transgene persistence and hematologic stability (absence of BMF or hematologic malignancy).
3. To determine long-term clonality patterns beyond the 3-year follow-up stipulated in the RP-L102 parent studies (RP-L102-0418, RP-L102-0319, RP-L102-0118).
4. To evaluate, when relevant, RCL in serum and peripheral blood cells (this will not be considered relevant for subjects in whom no evidence of RCL was identified during the initial year following investigational autologous cell infusion).
5. To determine the long-term stability and normalization of blood counts in patients subsequent to infusion of autologous FANCA-corrected hematopoietic cells.
6. To determine the phenotypic correction of BM and PB cells (as evaluated by resistance to DNA-damaging agents) in long-term follow-up after gene therapy.
7. To enable preliminary assessment of the incidence of hematologic malignancies (including AML/MDS) and solid organ tumors (including squamous cell carcinoma of the head and neck); occurrence of these events will be evaluated in the context of the underlying rates of these malignancies in FA patient populations (both those who have not undergone allogeneic stem cell transplant and FA patients post-HSCT).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Rocket Pharmaceuticals Inc.

Sponsor organisation

Rocket Pharmaceuticals Inc.

Address

9 Cedarbrook Dr, East Windsor East Windsor

City

Cranbury

Postcode

08512-3618

Country

United States

Scientific contact point

Organisation

Rocket Pharmaceuticals Inc.

Contact name

Patient Advocacy

Public contact point

Organisation

Rocket Pharmaceuticals Inc.

Contact name

Patient Advocacy

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 57 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications