FIH Study of DNL310 in paediatric patients with Hunter Syndrome

  • Research type

    Research Study

  • Full title

    A Phase 1/2, Multicenter, Open-Label Study to Determine The Safety, Pharmacokinetics, and Pharmacodynamics of DNL310 in Pediatric Participants with Hunter Syndrome

  • IRAS ID

    281907

  • Contact name

    May Young

  • Contact email

    myoung@dnli.com

  • Sponsor organisation

    Denali Therapeutics, Inc.

  • Eudract number

    2019-004909-27

  • Clinicaltrials.gov Identifier

    NCT04251026

  • Clinicaltrials.gov Identifier

    139904, IND

  • Duration of Study in the UK

    2 years, 4 months, 2 days

  • Research summary

    Mucopolysaccharidosis type II (MPS II or Hunter Syndrome), is a rare genetic condition that occurs almost exclusively in boys. MPS II is caused by lack of an enzyme resulting in accumulation of certain sugars in the body, causing abnormalities in many organs, including the skeleton, heart, and respiratory systems. In severe cases, this leads to early death.
    There is no cure for MPS II. Approved enzyme replacement therapies (ERT) may improve some symptoms of MPS II, especially if started early in the disease. However, as ERT cannot cross the blood–brain barrier, it does not treat the cognitive impairment in patients with central nervous system (CNS) symptoms. There is still a high, unmet medical need for improved treatment of MPS II.
    The proposed DNLI-E-0002 phase 1/2 open label study will evaluate the safety of DNL310 and establish a dose which will be well-tolerated by patients.
    DNL310 is an investigational medicine (not yet approved by regulatory authorities) which has not been previously given to humans. DNL310 will be given intravenously once a week. If DNL310 works as expected, it may help to reduce patients’ CNS and physical symptoms of MPS II.
    About 16 patients, age 2 to 18 years old, with confirmed MPS II, who meet study eligibility criteria will take part in the study, at approximately 10 sites in US and Europe. The study consists of 2 parts: main and safety extension. Patients will remain in the main part for approximately 7 months and in the safety extension for approximately 18 months. Depending on patient’s age and the time he enrols, patient will be assigned to treatment group A or B.
    During the study patients will undergo assessments which include physical exams, cognitive and behavioural assessments, blood, urine, cerebrospinal fluid analysis, hearing test, electrocardiogram, ultrasound and scales and questionnaires.

  • REC name

    North East - Newcastle & North Tyneside 1 Research Ethics Committee

  • REC reference

    20/NE/0151

  • Date of REC Opinion

    22 Jul 2020

  • REC opinion

    Further Information Favourable Opinion