Long-Term Follow-Up (LTFU) for Gene Therapy of Pyruvate Kinase Deficiency (PKD): A Phase I Clinical Trial to Evaluate the Safety of the Infusion of Autologous CD34+ Cells Transduced with a Lentiviral Vector Carrying the Codon Optimized Red Cell Pyruvate Kinase (coRPK) Gene in Adult and Pediatric Subjects with PKD

2022-501526-38-00 Protocol RP-L301-0222-LTFU Human pharmacology (Phase I) - Other Ongoing, recruitment ended

Start 6 Jun 2023 · Status Ongoing, recruitment ended · 1 EU/EEA countries · 2 sites · Protocol RP-L301-0222-LTFU

Overview

Sponsor-declared trial summary

Phase Human pharmacology (Phase I) - Other
Status Ongoing, recruitment ended
Participants planned 5
Countries 1
Sites 2

Pyruvate kinase deficiency

• To evaluate long-term safety following infusion of autologous CD34+ cells transduced with the therapeutic LV. • To determine the long-term persistence of the transgene in mononuclear cells in the blood, and to evaluate potential correlations between transgene persistence and transfusion independence (when relevant), …

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] - Hemic and Lymphatic Diseases [C15]
Trial duration
6 Jun 2023 → ongoing
Decision date (initial)
2023-01-09
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

• To evaluate long-term safety following infusion of autologous CD34+ cells transduced with the therapeutic LV.
• To determine the long-term persistence of the transgene in mononuclear cells in the blood, and to evaluate potential correlations between transgene persistence and transfusion independence (when relevant), reduction in transfusion requirements (when relevant), and clinically significant reduction of anemia.
• To determine long-term clonality patterns beyond the RP-L301 parent study (RP-L301-0119).
• To assess, 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).

Conditions and MedDRA coding

Pyruvate kinase deficiency

VersionLevelCodeTermSystem organ class
21.1 PT 10037682 Pyruvate kinase deficiency anaemia 100000004850

Regulatory references

Plan to share IPD
No
EU CT numberTitleSponsor
2019-001656-19 Gene Therapy for Pyruvate Kinase Deficiency (PKD): A Phase I Clinical Trial to Evaluate the Safety of the Infusion of Autologous CD34+ Cells Transduced with a Lentiviral Vector Carrying the Codon Optimized Red Cell Pyruvate Kinase (coRPK) Gene in Adult and Pediatric Subjects with PKD., Terapia génica para la deficiencia de piruvato quinasa (PKD): un ensayo clínico de fase I para evaluar la seguridad de la infusión de células CD34 + autólogas transducidas con un vector lentiviral que contiene el gen de piruvato quinasa de glóbulos rojos (CoRPK) con optimización de codones en sujetos adultos y pediátricos con PKD

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

  1. Patient was enrolled in the parent Study RP-L301-0119
  2. Patient received an autologous infusion of CD34+ enriched cells transduced ex vivo with a lentiviral vector carrying the coRPK gene
  3. Patient is willing and able to adhere to the study visit schedule and other protocol requirements
  4. Patient 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 for the current study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 7

  1. Overall survival
  2. Peripheral blood genetic correction, as demonstrated by vector copy number (VCN)
  3. Any red blood cell transfusion
  4. Sustained and significant decrease in hemoglobin unrelated to infection or surgery
  5. Adverse events related to worsening iron overload (for example, cirrhosis, cardiomyopathy, etc.)
  6. Any adverse event considered at least possibly related to RP-L301
  7. Development of any malignancy

Investigational products

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

Test 1

Merilen

PRD7873153 · Product

Active substance
Autologous CD34 Hematopoietic Stem Cells Transduced Ex Vivo with a Lentiviral Vector Encoding the Codon-Optimized Version of Pklr Gene
Pharmaceutical form
INFUSION
Route of administration
INTRAVENIOUS INFUSION
Authorisation status
Not Authorised
ATC code
B05AX — -
MA holder
ROCKET PHARMACEUTICALS, INC
Paediatric formulation
No
Orphan designation
Yes
Orphan designation number
EU/3/14/1330

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

Third parties 6

OrganisationCity, countryDuties
Intrinsic Lifesciences LLC
ORG-100044000
La Jolla, United States Laboratory analysis
Premier Research Group S.L.
ORG-100013963
Madrid, Spain On site monitoring, Code 12, Code 5, Data management, E-data capture, Code 8
Patient Primary - MDgroup
ORL-000000903
Durham, United States Other
PPD Global Central Labs
ORG-100046496
Zaventem, Belgium Laboratory analysis
Medizinische Hochschule Hannover
ORG-100024473
Hanover, Germany Laboratory analysis
Indiana University Gene Therapy Testing Laboratory
ORL-000000975
Indianapolis, United States Laboratory analysis

Locations

1 EU/EEA country · 2 investigational sites

By country

CountryMS statusPlanned subjectsSites
Spain Ongoing, recruitment ended 4 2
Rest of world
United States
1

Investigational sites

Spain

2 sites · Ongoing, recruitment ended
Hospital Infantil Universitario Nino Jesus
Onco Hematology, Avenida Menendez Pelayo 65, 28009, Madrid
Hospital Universitario Fundacion Jimenez Diaz
Hematology, Avenida De Los Reyes Catolicos 2, 28040, Madrid

Country notifications

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

Country Trial startTrial end Recruitment startRecruitment end Early termination
Spain 2023-06-06 2023-09-11 2025-09-08

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2022-09-20 Spain Acceptable
2022-11-02
2023-01-09
2 SUBSTANTIAL MODIFICATION SM-1 2023-01-10 Spain Acceptable 2023-01-13
3 NON SUBSTANTIAL MODIFICATION NSM-2 2023-04-13 Spain Acceptable 2023-04-13
4 SUBSTANTIAL MODIFICATION SM-2 2024-01-10 Spain Acceptable
2024-02-23
2024-02-27
5 SUBSTANTIAL MODIFICATION SM-4 2025-02-21 Spain Acceptable
2025-04-21
2025-04-22