Gene therapy study with autologous hematopoietic stem cells for patients affected by MPS-IH

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Orchard Therapeutics (Europe) Limited

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Phenomena and Processes [G] - Genetic Phenomena [G05]

Trial duration

14 May 2018 → ongoing

Decision date (initial)

2024-07-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Orchard Therapeutics (Europe) Ltd

External identifiers

EU CT number

2024-514870-29-00

EudraCT number

2017-002430-23

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the safety and tolerability of autologous CD34+ cell enriched fraction that contains HSPC transduced with lentiviral vector (LVV) encoding the IDUA gene in pediatric patients with MPS-IH following a myeloablative and lymphoablative conditioning regimen.

Secondary objectives 1

1. To evaluate the efficacy of autologous CD34+ cell enriched fraction that contains HSPC transduced with LVV encoding the IDUA gene in pediatric patients with MPS-IH following a myeloablative and lymphoablative conditioning regimen

Conditions and MedDRA coding

Mucopolysaccharidosis type I Hurler

Study design 5 periods

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-003001-PIP01-21

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Written informed consent by parent/legal guardian
2. Sex: Males and Females
3. ≥ 28 days and ≤ 11 years old
4. Biochemically and molecularly proven MPS-IH
5. Lansky Index > 80 %
6. Indication to HSCT
7. Lack of a non-heterozygous (for mutated IDUA) human leukocyte antigens (HLA) -matched sibling donor or a ≥7/8 (4 digits high-resolution typing) HLA-matched cord blood donor with a cellularity ≥5x10^7 Total Nucleated Cells (TNC)/Kg after 1-month search. This criterion will not apply to patients whose country of origin does not offer unrelated donor cord blood transplantation.
8. Adequate cardiac, renal, hepatic and pulmonary functions

Exclusion criteria 10

1. Use of other investigational agents within 4 weeks prior to study enrolment (within 6 weeks if use of long-acting agents)
2. Severe, active viral, bacterial, or fungal infection at eligibility evaluation
3. Patients affected by malignant neoplasia or family history of familial cancer syndromes
4. Cytogenetic alterations associated with high risk of developing hematological malignancies
5. History of uncontrolled seizures
6. Patients with end-organ damage or any other severe disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study
7. Positivity for HIV (serology or RNA), and/or HbsAg and/or HBV DNA and/or HCV RNA and/or Treponema Pallidum or Mycoplasma active infection
8. Patients with DQ/IQ <70 (also referred as, “cognitive standard score”, measured using Cognitive Scale for Bayley Scale of Infant Development and Performance IQ for WPPSI and WISC)
9. Previous allogeneic HSCT or gene therapy with a different product
10. Controindications to Products equivalent to the IMP (PeIMP): G-CSF, Plerixafor, Busulfan, Fludarabine, Rituximab

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

1. Overall survival from Advanced Therapy Investigational Medicinal Product (ATIMP) injection
2. Achievement of hematological engraftment less than or equal to day +45 from Advanced Therapy Investigational Medicinal Product (ATIMP) injection. Hematologic engraftment is defined as the first of 3 consecutive days with neutrophil count > 500/mm3 and platelets > 20,000/mm3 (in the absence of platelet transfusion for seven consecutive days).
3. Safety of the administration of autologous HSPC transduced with LVV-IDUA. This will be measured as: a) short-term tolerability (0-24 hours from ATIMP injection); b) absence of Replication Competent Lentivirus (RCL); c) absence of malignancy or abnormal clonal proliferation due to insertional mutagenesis.
4. Overall safety and tolerability measured by Adverse Event (AE) recording.
5. IDUA activity in blood (dried blood spot, DBS) (up to supraphysiologic levels) at 1-year posttreatment

Secondary endpoints 7

1. Achievement of supraphysiologic IDUA activity in blood (DBS)
2. IDUA activity in plasma
3. Engraftment of transduced cells >= 0.30 vector copy number (VCN)/genome
4. Normalization of urinary GAGs
5. Normalization of spleen and liver (for age)
6. Growth velocity
7. Anti-IDUA antibody immune response before and after infusion of IDUA LVV-transduced cells

Investigational products

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

Test 1

Auxiliary 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Orchard Therapeutics (Europe) Limited

Sponsor organisation

Orchard Therapeutics (Europe) Limited

Address

245 Hammersmith Road

City

London

Postcode

W6 8PW

Country

United Kingdom

Scientific contact point

Organisation

Orchard Therapeutics (Europe) Limited

Contact name

Clinical

Public contact point

Organisation

Orchard Therapeutics (Europe) Limited

Contact name

Clinical

Third parties 7

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 13 files

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

Application history

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