Patient case (clinical description): An 8-year-old boy is brought to the clinic by his parents because of weakness and difficulty of standing up from a sitting position. The mother is healthy but had a brother who died in his 20th after being disabled and using wheelchairs in the last few years of his life. Physical examination shows 3/5 lower extremity muscle strength and enlarged calf muscles. The other physical examination and vital signs are unremarkable. Muscle biopsy showed absence of dystrophin protein. The patient is diagnosed with DMD.

Patient's own account: I brought my  8-year-old son to the doctor's clinic. He was struggling to stand up from a chair for the past few days. My wife is healthy but she was pretty worried since his brother died in his 20s after being disabled and using a wheelchair for the last years of his life. The doctor did an exam which highlighted weakness in the leg muscles and unusually large calf muscles. The rest of the exam was fine, and his vitals were normal. My son did a muscle biopsy, and it showed that the protein important for muscle strength and function is missing. The doctor diagnosed him with Duchenne muscular dystrophy.

Clinical trial: Proof of Concept Study to Assess Activity and Safety of SMT C1100 (Ezutromid) in Boys With Duchenne Muscular Dystrophy (DMD)

Eligibility criteria:
Inclusion Criteria:

          -  Be able to provide written informed consent/assent as per local requirements.

          -  Be male.

          -  Have phenotypic evidence of dystrophinopathy based on the onset of characteristic
             clinical symptoms or signs (e.g., proximal muscle weakness, waddling gait, and Gowers'
             manoeuvre), an elevated serum creatinine kinase level, and ongoing difficulty with
             walking.

          -  Have prior confirmation of the duchenne muscular dystrophy (DMD) diagnosis through:

        Documentation of the presence of a mutation in the dystrophin gene as determined by gene
        sequencing from a laboratory certified by the College of American Pathologists, the
        Clinical Laboratory Improvement Act/Amendment or an equivalent organisation or
        documentation of the absence of dystrophin in the muscle (via biopsy).

          -  Be able to undergo MRI examination.

          -  Participants must have used stable systemic corticosteroids (prednisone, prednisolone
             or deflazacort) for a minimum of 6 months immediately prior to the start of the
             Treatment Phase, with no significant change in dosage or dosing regimen (not related
             to body weight change) and a reasonable expectation that dosage and dosing regimen
             will not change significantly for the duration of the study.

          -  Confirmed screening laboratory values within the central laboratory ranges
             (haematology, renal and serum electrolyte parameters and serum chemistry parameters)
             or considered not clinically significant in the opinion of the Investigator.
             Variations in specific parameters expected in a DMD population classed by the
             Investigator as not clinically significant will not exclude the participant.

          -  Be willing and able to comply with scheduled visits, drug administration plan, study
             procedures, laboratory tests and study restrictions.

        Cohort 1 and 2 Specific Inclusion Criteria:

          -  Be aged ≥5 years to <10 years of age (from 5th birthday to 10th birthday).

          -  Be willing and able to comply with 2 muscle biopsy procedures.

          -  Have the ability to walk at least 300 meters unassisted during the screening 6 minute
             walk distance (6MWD) and be below the protocol-specified threshold for 80%-predicted
             6MWD.

          -  Have results of 2 6MWD by Baseline determined as valid. The results of the second 6MWD
             (baseline) must be within 20% of the first 6MWD (screening).

          -  Have cardiac echocardiogram (ECHO) measurements showing an ejection fraction of ≥55%
             and fractional shortening of ≥28%.

        Cohort 3 Specific Inclusion Criteria:

          -  Have taken part in a prior SMT C1100 study.

        Exclusion Criteria:

          -  Have physical exam findings that in the Investigator's opinion should be exclusionary
             e.g., lower limb injury that may affect 6MWD performance.

          -  Have any change (initiation, change in type of drug, dose modification, schedule
             modification, interruption, discontinuation or reinitiation) in prophylaxis/treatment
             for congestive heart failure (CHF) within 3 months prior to the start of study
             treatment.

          -  Have uncontrolled clinical symptoms and signs of CHF (American College of
             Cardiology/American Heart Association Stage C or Stage D).

          -  Have abnormal glutamate dehydrogenase (GLDH) at baseline (>1.5 x upper limit of normal
             [ULN]).

          -  Have abnormal coagulation times at baseline (>1.5 x ULN).

          -  Have an abnormal electrocardiograms (ECG).

          -  Use herbal supplements and be unwilling to stop these for the duration of the study.

          -  Have been exposed to another investigational drug or DMD interventional agent within 3
             months prior to start of the Treatment Phase. Prior exposure to SMT C1100 or
             participation in an approved deflazacort access program within this period would not
             exclude the participant (provided they have been on stable treatment for 6 months).

          -  Have a history of major surgical procedure within 12 weeks prior to the start of the
             Treatment Phase (Week 1).

          -  Be undertaking ongoing immunosuppressive therapy (other than corticosteroids).

          -  Require daytime ventilator assistance.

          -  Have a prior or ongoing medical condition, medical history, ECG findings, or
             laboratory abnormality that, in the Investigator's opinion, could adversely affect the
             safety of the participant, makes it unlikely that the course of treatment or follow-up
             would be completed, or could impair the assessment of study results.

          -  Be dairy or lactose intolerant or have any other dietary restrictions that might
             interfere with the conduct of the study.

          -  Be a smoker, use other tobacco or nicotine products or be exposed to daily passive
             smoking (including parent/legal guardian, siblings) so as to minimise environmental
             factors causing CYP1A induction.

          -  Be using an approved DMD medication or anticipates using one during the duration of
             the study. Participants who are taking part in the FOR-DMD and ACCESS DMD studies will
             be allowed to take part.

          -  Be using an inducer of CYP1A1 or CYP1A2.

          -  Be using a substrate of CYP2B6.

          -  All prescription, over the counter, and herbal products that are known CYP2B6
             sensitive substrates will be excluded 14 days prior to study conduct (beginning at
             screening) through 14 days after study conduct completion. Please note, this is not an
             exhaustive list of CYP2B6 substrates and a discussion with the Medical Monitor may be
             warranted.

          -  Be using drugs that have serotonergic, norepinephrinergic or dopaminergic activity, or
             treatments used in attention deficit hyperactivity disorder.

          -  Use of substrates of BRCP.

        Cohort 1 and 2 Specific Exclusion Criteria:

          -  Use beta blockers (however, if during the course of the study they are clinically
             indicated they can be initiated).

        Cohort 1 and 3 Specific Exclusion Criteria:

          -  Have a known hypersensitivity to any of the ingredients or excipients of the
             investigational medicinal product: Poloxamer 188, Methylparaben, Propylparaben,
             Hydroxypropylmethyl cellulose, Glycerol, Non-crystallising sorbitol [70%], Xanthan
             gum, Strawberry cream flavour [PHS-132963].

        Cohort 2 Specific Exclusion Criteria:

          -  Have a known hypersensitivity to any of the ingredients or excipients of the
             investigational medicinal product: hypromellose acetate succinate.
Male
No healthy subjects accepted to join the trial.
Subject must be at least 5 Years old.


Eligibility (NLI label): Entailment