Phase I/II study of weekly infusions of JR-441 in patients with mucopolysaccharidosis type IIIA

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Jcr Pharmaceuticals Co. Ltd.

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

26 Sep 2023 → ongoing

Decision date (initial)

2024-09-13

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

JCR Pharmaceuticals Co., Ltd.

External identifiers

EU CT number

2024-517045-14-00

EudraCT number

2022-002314-17

ClinicalTrials.gov

NCT06095388

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Others, Safety, Pharmacokinetic, Dose response

To evaluate the safety and explore efficacy of JR-441 in development for the treatment of MPS IIIA patients.

Conditions and MedDRA coding

Mucopolysaccharidosis type IIIA (MPS IIIA)

Regulatory references

Scientific advice from competent authorities

Paul-Ehrlich-Institut

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. (1) Chronological age of ≥1 year and ≤18 years at the time of signing ICF.
2. (2) A participant who voluntarily signs an IRB or IEC-approved written ICF. If the participant is aged 1year to <18 years at the time of informed consent, or willingness to participate in the study cannot be confirmed due to MPS IIIA-related intellectual disability, the participant’s legally acceptable representative (e.g., his/her parents or guardians) may sign the ICF on behalf of the participant. Written informed assent must be obtained from the participant, wherever possible..
3. (3) A participant with a confirmed diagnosis of MPS IIIA, based on all the following criteria: ○ Activity of the N-sulphoglucosamine sulphohydrolase (SGSH) enzyme below 10% of the lower reference level in white blood cells or cultured skin fibroblasts. ○ A normal enzyme activity level of at least one other sulfatase (to rule out multiple sulfatase deficiency) as measured in leukocytes. ○ Presence of a pathological mutation in each of the individual alleles of the SGSH gene. Note: if SGSH enzyme activity results are abnormal (i.e., below the normal range of the assay) but still above the threshold of 10% of the lower reference level, MPS IIIA diagnosis may be confirmed based on family history and genotype following discussion and approval from the sponsor’s Medical Monitor.
4. (4) Study participants should have a minimal body weight of 10 kg.
5. (5) Female participants of childbearing potential or participants whose female partner is of child-bearing potential agree to use a medically accepted, highly effective method of contraception as described in Section 10.5, from the time of signing the ICF. The method of contraception must be used during the study until 90 days for male participants, and 30 days for female participants after the final study drug administration or vasectomy at least 13 weeks prior to signing ICF..
6. (6) For participants with hearing impairment requiring hearing aid(s), every effort has been made to encourage compliance with the use of functioning hearing aid(s) before baseline neurodevelopmental assessments, and parent/legally acceptable representative or participant agrees to encourage wearing them during the study and on neurodevelopmental function test days.
7. (7) Medically stable and able to accommodate the protocol requirements, including travel without placing an undue burden on the participant/participant’s family, as determined by the principal investigator.

Exclusion criteria 19

1. (1) A participant who has received gene therapy treatment or hematopoietic stem cell transplantation (HSCT) with successful engraftment.
2. (2) A participant who is pregnant or breast feeding.
3. (3) A participant who has received another investigational drug or product within 4 months or 5 half-lives (whichever is longer) before the time of providing informed consent.
4. (4) A participant who is participating concurrently or who has participated prior (within 30 days of enrolment into this study) in a study involving invasive procedures.
5. (5) A participant who has received Genistein within 4 months before the time of providing informed consent.
6. (6) A participant who has received KINERET® (anakinra) within 4 months before the time of providing informed consent.
7. (7) A participant who has developed serious drug allergy or hypersensitivity to any components of JR-441 or medications likely prescribed during the study, which, in the opinion of the principal investigator or sub-investigator, would be an impediment towards completion of the study.
8. (8) A participant unable to undergo lumbar puncture.
9. (9) A participant unable to undergo MRI.
10. (10) A participant who has had a ventriculoperitoneal (VP) shunt placed or any other brain surgery
11. (11) A participant has a history of bleeding disorder or current use of medications that, in the opinion of the investigator, place them at risk of bleeding following lumbar puncture.
12. (12) A participant who has a history of poorly controlled seizures.
13. (13) Serology consistent with human immunodeficiency virus (HIV) exposure or consistent with active hepatitis B (HepB) or C (HepC) infection.
14. (14) A participant who has lab abnormalities with CTCAE grade ≥ II for liver function test, bilirubin, creatinine, hemoglobin, white blood cell count, platelet count, prothrombin time, and activated partial thromboplastin time (aPTT), except subject whose bilirubin elevated due to Gilbert’s Syndrome.
15. (15) A participant with known iron-metabolism disorder.
16. (16) A participant with visual or hearing impairment sufficient, in the clinical judgment of the principal investigator or sub-investigator, to preclude cooperation with neurodevelopmental testing.
17. (17) A participant currently receiving psychotropic or other medications which in the principal investigator’s or sub-investigator’s opinion, would be likely to substantially confound test results.
18. (18) A participant who has a medical condition or extenuating circumstance that, in the opinion of the principal investigator or sub-investigator, might compromise the participant’s ability to comply with protocol requirements, the participant’s well-being or safety, or the interpretability of the participant’s clinical data.
19. (19) A participant who is ineligible to participate in the study in the opinion of the principal investigator or sub-investigator.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

1. 1. Occurrence of adverse events (AEs)
2. 2. Changes in safety laboratory tests (hematology, coagulation, blood biochemistry, iron-related tests, and urinalysis)
3. 3. Changes in vital signs (pulse rate, body temperature, blood pressure, respiratory rate, and percutaneous oxygen saturation)
4. 4. Changes in 12-lead electrocardiogram (ECG)
5. 5. Number and severity of infusion-associated reactions (IARs), occurrence of anaphylaxis

Secondary endpoints 3

1. 1. Plasma drug concentration
2. 2. Plasma PK parameters
3. 3. Changes in the following parameters from baseline to each evaluation time point: (1) Heparan sulfate (HS concentration in CSF and serum, and HS concentration relative to creatinine concentration in urine. (2) Cognitive function assessed by Cognitive scales and/or Nonverbal Index (NVI); (3) Adaptive behavior assessment

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Jcr Pharmaceuticals Co. Ltd.

Sponsor organisation

Jcr Pharmaceuticals Co. Ltd.

Address

3-19 Kasugacho

City

Ashiya

Postcode

659-0021

Country

Japan

Scientific contact point

Organisation

Jcr Pharmaceuticals Co. Ltd.

Contact name

JCR Pharmaceuticals Co. Ltd

Public contact point

Organisation

Jcr Pharmaceuticals Co. Ltd.

Contact name

JCR Pharmaceuticals Co. Ltd

Third parties 10

Sponsor responsibilities

Article 77 compliance

Jcr Pharmaceuticals Co. Ltd.

Contact point sponsor

Jcr Pharmaceuticals Co. Ltd.

Article 77 implementation

Jcr Pharmaceuticals Co. Ltd.

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 20 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