Duchenne Muscular DystrophyPhase 2NCT02858362

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

A Phase 2 study testing Ezutromid in people with Duchenne Muscular Dystrophy, run by Summit Therapeutics at 16 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

To Assess the Activity and Safety of SMT C1100 (Ezutromid) in Paediatric Male Participants with Duchenne Muscular Dystrophy (DMD). Read more about this study

Who is it for?: Ages 5 years and older, men only
Conditions the study is for: Duchenne Muscular Dystrophy
What is being tested?: Ezutromid
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 43 participants
Where: 16 sitesin 2 countries
Study dates: Jun 2016to 11 Sep 2018
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 5 years and older
Men only
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

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.

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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.

Who cannot join

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).

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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.

Trial locations and contacts

16 sites in 2 countries.

Country

City, postcode or hospital

16 sites in 2 countries

United States9 sites

Children's Hosptial of Colorado
Aurora, Colorado
Boston Children's Hospital
Boston, Massachusetts
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio
UCLA-David Geffen School of Medicine
Los Angeles, California
Vanderbilt University Medical Center
Nashville, Tennessee
Nemours Children's Clinic
Orlando, Florida
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania
Oregon Health and Science University
Portland, Oregon
University of Utah Hospital and Clinics
Salt Lake City, Utah

Other trials in United States

United Kingdom7 sites

Heart of England NHS Foundation Trust - Heartlands Hospital
Birmingham
Bristol Children's Hospital
Bristol
Addenbrooke's Hospital
Cambridge
Alder Hey Children's NHS Foundation Trust
Liverpool
Great Ormond Street Hospital for Children NHS Foundation Trust
London
Royal Manchester Children's Hospital - Central Manchester University Hospitals NHS Foundation Trust
Manchester
The Freeman Hospital, Newcastle Upon Tyne Hospitals
Newcastle

Other trials in United Kingdom

About this study

Official title: Phaseout DMD: A Phase 2 Clinical Study to Assess the Activity and Safety of Utrophin Modulation With Ezutromid in Ambulatory Paediatric Male Subjects With Duchenne Muscular Dystrophy (SMT C11005)

To Assess the Activity and Safety of SMT C1100 (Ezutromid) in Paediatric Male Participants with Duchenne Muscular Dystrophy (DMD).

Read the detailed description

This is a Phase 2, open label, study to assess the activity and safety of utrophin modulation with SMT C1100 (ezutromid) administered twice-daily orally in ambulatory paediatric male participants with DMD.

This study will be conducted in a multi-centre setting in both the United Kingdom and the United States of America and comprises of a Screening and Baseline Phase of up to 28 days, a 48-week open label Treatment Phase, and either a 30-day Safety Follow up Phase or an optional extension phase where study treatment is provided until discontinuation of the program or regulatory approvals as applicable.

Conditions: Duchenne Muscular Dystrophy
Being tested: Ezutromid
Keywords: DMD, Muscular Dystrophy, Utrophin, Duchenne, PhaseOut DMD
Medical subject headings: Muscular Dystrophy, Duchenne, Muscular Dystrophies

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

EzutromidDrug
Also called SMT C1100
Administered orally.

Study groups in NCT02858362
Study group	Role	What they receive
Cohort 1: SMT C1100 Formulation 1	Experimental	Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Receives: Drug: Ezutromid
Cohort 2: SMT C1100 Formulation 2	Experimental	Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks. Receives: Drug: Ezutromid
Cohort 3: SMT C1100 Formulation 1	Experimental	Participants in this cohort had previously received SMT C1100, but were not eligible for Cohorts 1 or 2. Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Receives: Drug: Ezutromid

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline in Magnetic Resonance Spectroscopy (MRS) Fat Fraction (FF) for Leg Muscles
MRS FF was analysed for vastus lateralis and soleus leg muscles. The endpoints were measured for Cohorts 1 and 2 only. Results for Cohorts 1 and 2 are pooled as specified in the protocol.
Measured: Baseline, Week 12, Week 24, Week 36 and Week 48
Change From Baseline for Magnetic Resonance Spectroscopy (MRS) Water Transverse Relaxation Time (WTRT) for Leg Muscles
MRS WTRT was analysed for the vastus lateralis and soleus leg muscles. The endpoints were measured for Cohorts 1 and 2 only. Results for Cohorts 1 and 2 are pooled as specified in the protocol.
Measured: Baseline, Week 12, Week 24, Week 36 and Week 48
Observed Trough Plasma Concentration (Ctrough) for SMT C1100, Dihydrodiol 1 (DHD1) and Dihydrodiol III (DHD 3)
Pharmacokinetic analysis is presented by cohort due to the use of different formulations. The median pre-dose concentration was derived for each participant and then summarized across participants.
Measured: Pre-dose at Weeks 1, 4, 8, 12, 24, 36 and 48
Simulated Maximum Plasma Concentration (Cmax) for SMT C1100, Dihydrodiol 1 (DHD1) and Dihydrodiol III (DHD 3)
Pharmacokinetic analysis is presented by cohort due to the use of different formulations.
Measured: Pre-dose and 3 to 10 hours post-dose at Weeks 1, 4, 8, 12, 24, 36 and 48
Simulated Average Plasma Concentration (Cav) for SMT C1100, Dihydrodiol 1 (DHD1) and Dihydrodiol III (DHD 3)
Pharmacokinetic analysis is presented by cohort due to the use of different formulations.
Measured: Pre-dose and 3 to 10 hours post-dose at Weeks 1, 4, 8, 12, 24, 36 and 48
Number of Participants Reporting One or More Treatment-Emergent Adverse Events (TEAEs)
An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. A TEAE is defined as any event not present before exposure to study drug or any event already present that worsens in either intensity or frequency after exposure to study drug.
Measured: Day 1 to a maximum of Week 96

Secondary outcomes (19)

Change From Baseline in Utrophin Intensity
A maximum of two muscle biopsies were taken, one at baseline and the other at Week 24 or Week 48. Utrophin intensity was analyzed using a semiautomated quantitative assay on the biopsy samples. A positive change from baseline represents an increase in utrophin expression, no change from baseline represents maintenance of utrophin expression and a negative change from baseline represents a reduction in utrophin expression. The endpoint was measured for Cohorts 1 and 2 only. Results for Cohorts 1 and 2 are pooled as specified in the protocol.
Measured: Baseline, Week 24 and Week 48
Change From Baseline in Developmental Heavy Chain Myosin (MHCd) Expression
A maximum of two muscle biopsies were taken, one at baseline and the other at Week 24 or Week 48. MHCd expression was analyzed using a semiautomated quantitative assay on the biopsy samples. A positive change from baseline represents an increase in MHCd expression, no change from baseline represents maintenance of MHCd expression and a negative change from baseline represents a reduction in MHCd expression. The endpoint was measured for Cohorts 1 and 2 only. Results for Cohorts 1 and 2 are pooled as specified in the protocol.
Measured: Baseline, Week 24 and Week 48
Change From Baseline in Muscle Fibre Diameter
A maximum of two muscle biopsies were taken, one at baseline and the other at Week 24 or Week 48. Muscle fibre diameter was analyzed using a semiautomated quantitative assay on the biopsy samples. The endpoint was measured for Cohorts 1 and 2 only. Results for Cohorts 1 and 2 are pooled as specified in the protocol.
Measured: Baseline, Week 24 and Week 48
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)
Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.
Measured: Baseline, Week 12, Week 24, Week 36 and Week 48
Change From Baseline in Forced Vital Capacity (FVC)
Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.
Measured: Baseline, Week 12, Week 24, Week 36 and Week 48
Change From Baseline in Maximum Inspiratory Pressure (MIP)
Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.
Measured: Baseline, Week 12, Week 24, Week 36 and Week 48
Change From Baseline in Maximum Expiratory Pressure (MEP)
Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.
Measured: Baseline, Week 12, Week 24, Week 36 and Week 48
Change From Baseline in Peak Expiratory Flow (PEF)
Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.
Measured: Baseline, Week 12, Week 24, Week 36 and Week 48
Change From Baseline in Peak Cough Flow (PCF)
Analysis of PCF was planned for Cohort 3 only.
Measured: Baseline, Week 12, Week 24, Week 36 and Week 48
Change From Baseline in Sniff Nasal Inspiratory Pressure (SNIP)
Analysis of SNIP was planned for Cohort 3 only.
Measured: Baseline, Week 12, Week 24, Week 36 and Week 48
Number of Participants That Experienced a Clinically Significant Change in Vital Signs Measurements
Systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse will be disclosed with the following categories:
- All values within 20% of change from baseline (< 20% change).
- At least one value ≥ 20% reduction from baseline, but no increases ≥ 20% from baseline (≥ 20% reduction and no < 20% increase).
- At least one value ≥ 20% increase from baseline, but no reductions ≥ 20% from baseline (≥ 20% Increase and no < 20% reduction).
- At least one value ≥ 20% reduction from baseline and at least one value ≥ 20% increase from baseline (≥ 20% reduction and ≥ 20% increase).
Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.
Measured: Baseline to Week 48
Number of Participants That Experienced a Clinically Significant in Physical Examination Result
Examinations included: ear, nose and throat, cardiovascular system, pulmonary system, skin, abdomen, neurological system, height and weight. Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.
Measured: Day 1 to Week 48
Number of Participants That Experienced a Potentially Clinically Significant Electrocardiogram Measurements
PR interval (PRI), heart rate (HR), QTcF and increase from baseline in QTcF (IQTcF) were summarized categorically. Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.
Measured: Baseline to Week 48
Number of Participants That Experienced a Potentially Clinically Significant Echocardiogram Measurement
Participants were at rest in a supine position for 10 minutes before the measurements were performed. Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.
Measured: Baseline, Week 24 and Week 48
Number of Participants That Experienced a Clinically Significant Haematology Result (Investigator's Assessment)
Parameters included: haemoglobin, haematocrit, mean corpuscular volume, white blood cells, red blood cells, neutrophils (percentage and absolute), lymphocytes (percentage and absolute), monocytes (percentage and absolute), eosinophils (percentage and absolute), basophils (percentage and absolute) and platelets. Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.
Measured: Day 1 to Week 48
Number of Participants Who Experienced a Clinically Significant Biochemistry Result (Investigator's Assessment)
Parameters included: calcium, potassium, sodium, albumin, urea nitrogen, uric acid, creatinine, creatine kinase, fasting glucose, cystatin C, lactate dehydrogenase, amylase, lipase, low density lipoprotein cholesterol, high density lipoprotein (HDL) cholesterol, cholesterol, non-HDL cholesterol, total HDL cholesterol ratio, total bilirubin, direct bilirubin, indirect bilirubin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase and glutamate dehydrogenase. Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.
Measured: Day 1 to Week 48
Number of Participants That Experienced a Potentially Clinically Significant Liver Function Result
Laboratory measurements for alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB), alkaline phosphatase (ALP), and glutamate dehydrogenase (GLDH). Hy's Law is defined as an increase in ALT, AST and TB, indicating hepatocyte necrosis and functional deficit. Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.
Measured: Baseline to Week 48
Number of Participants That Experienced a Clinically Significant Urinalysis Result (Investigator's Assessment)
Parameters included: glucose, bilirubin, ketones, specific gravity, blood, pH, protein, urobilinogen, nitrites and leucocytes. Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.
Measured: Day 1 to Week 48
Number of Participants That Experienced a Clinically Significant Coagulation Result (Investigator's Assessment)
Parameters included: activated partial thromboplastin time, prothrombin time and international normalised ratio. Coagulation was only assessed for Cohorts 2 and 3. Results for Cohorts 2 and 3 are pooled as specified in the protocol.
Measured: Day 1 to Week 48

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 201611 Sep 2018

First posted8 Aug 2016 (estimated)
Study startJun 2016
Primary completion11 Apr 2018
Study completion11 Sep 2018

Why it stopped: The study was terminated due to lack of efficacy in Cohorts 1 and 2.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Duchenne Muscular DystrophyStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 43 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02858362
Sponsor's protocol ID: SMT C11005
Other IDs: 2015-004333-27, 2015
Status last verified: Dec 2019
First submitted: 27 Jul 2016
Last updated: 2 Jan 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Duchenne Muscular Dystrophy trials

Study at a glance

From the registry record, last updated by the sponsor on 2 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phaseout DMD: A Phase 2 Clinical Study to Assess the Activity and Safety of Utrophin Modulation With Ezutromid in Ambulatory Paediatric Male Subjects With Duchenne Muscular Dystrophy (SMT C11005)
ClinicalTrials.gov ID: NCT02858362
Acronym / sponsor ID: SMT C11005
Conditions: Duchenne Muscular Dystrophy
Keywords: DMD, Muscular Dystrophy, Utrophin, Duchenne, PhaseOut DMD
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: The study was terminated due to lack of efficacy in Cohorts 1 and 2.
Enrolment: 43 participants (actual)
Lead sponsor: Summit TherapeuticsIndustry (pharma, biotech, devices)
Study start: Jun 2016 (actual)
Primary completion: 11 Apr 2018 (actual)
Study completion: 11 Sep 2018 (actual)
First posted: 8 Aug 2016 (estimated)
Results: Posted 2 Jan 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

To Assess the Activity and Safety of SMT C1100 (Ezutromid) in Paediatric Male Participants with Duchenne Muscular Dystrophy (DMD).

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Cohort 1: SMT C1100 Formulation 1	Experimental	Drug: EzutromidParticipants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
Cohort 2: SMT C1100 Formulation 2	Experimental	Drug: EzutromidParticipants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
Cohort 3: SMT C1100 Formulation 1	Experimental	Drug: EzutromidParticipants in this cohort had previously received SMT C1100, but were not eligible for Cohorts 1 or 2. Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.

Who may qualify

Ages: 5 years and older
Sex: Male only
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (17 listed)

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).

Key exclusion criteria (26 listed)

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).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
EzutromidAlso: SMT C1100Administered orally.	Drug	Cohort 1: SMT C1100 Formulation 1, Cohort 2: SMT C1100 Formulation 2, Cohort 3: SMT C1100 Formulation 1

Primary outcome

Change From Baseline in Magnetic Resonance Spectroscopy (MRS) Fat Fraction (FF) for Leg Muscles
Time frame: Baseline, Week 12, Week 24, Week 36 and Week 48
MRS FF was analysed for vastus lateralis and soleus leg muscles. The endpoints were measured for Cohorts 1 and 2 only. Results for Cohorts 1 and 2 are pooled as specified in the protocol.
Change From Baseline for Magnetic Resonance Spectroscopy (MRS) Water Transverse Relaxation Time (WTRT) for Leg Muscles
Time frame: Baseline, Week 12, Week 24, Week 36 and Week 48
MRS WTRT was analysed for the vastus lateralis and soleus leg muscles. The endpoints were measured for Cohorts 1 and 2 only. Results for Cohorts 1 and 2 are pooled as specified in the protocol.
Observed Trough Plasma Concentration (Ctrough) for SMT C1100, Dihydrodiol 1 (DHD1) and Dihydrodiol III (DHD 3)
Time frame: Pre-dose at Weeks 1, 4, 8, 12, 24, 36 and 48
Pharmacokinetic analysis is presented by cohort due to the use of different formulations. The median pre-dose concentration was derived for each participant and then summarized across participants.
Simulated Maximum Plasma Concentration (Cmax) for SMT C1100, Dihydrodiol 1 (DHD1) and Dihydrodiol III (DHD 3)
Time frame: Pre-dose and 3 to 10 hours post-dose at Weeks 1, 4, 8, 12, 24, 36 and 48
Pharmacokinetic analysis is presented by cohort due to the use of different formulations.
Simulated Average Plasma Concentration (Cav) for SMT C1100, Dihydrodiol 1 (DHD1) and Dihydrodiol III (DHD 3)
Time frame: Pre-dose and 3 to 10 hours post-dose at Weeks 1, 4, 8, 12, 24, 36 and 48
Pharmacokinetic analysis is presented by cohort due to the use of different formulations.
Number of Participants Reporting One or More Treatment-Emergent Adverse Events (TEAEs)
Time frame: Day 1 to a maximum of Week 96
An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. A TEAE is defined as any event not present before exposure to study drug or any event already present that worsens in either intensity or frequency after exposure to study drug.

19 secondary outcomes

Change From Baseline in Utrophin Intensity
Time frame: Baseline, Week 24 and Week 48
Change From Baseline in Developmental Heavy Chain Myosin (MHCd) Expression
Time frame: Baseline, Week 24 and Week 48
Change From Baseline in Muscle Fibre Diameter
Time frame: Baseline, Week 24 and Week 48
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)
Time frame: Baseline, Week 12, Week 24, Week 36 and Week 48
Change From Baseline in Forced Vital Capacity (FVC)
Time frame: Baseline, Week 12, Week 24, Week 36 and Week 48
Change From Baseline in Maximum Inspiratory Pressure (MIP)
Time frame: Baseline, Week 12, Week 24, Week 36 and Week 48
Change From Baseline in Maximum Expiratory Pressure (MEP)
Time frame: Baseline, Week 12, Week 24, Week 36 and Week 48
Change From Baseline in Peak Expiratory Flow (PEF)
Time frame: Baseline, Week 12, Week 24, Week 36 and Week 48
Change From Baseline in Peak Cough Flow (PCF)
Time frame: Baseline, Week 12, Week 24, Week 36 and Week 48
Change From Baseline in Sniff Nasal Inspiratory Pressure (SNIP)
Time frame: Baseline, Week 12, Week 24, Week 36 and Week 48
Number of Participants That Experienced a Clinically Significant Change in Vital Signs Measurements
Time frame: Baseline to Week 48
Number of Participants That Experienced a Clinically Significant in Physical Examination Result
Time frame: Day 1 to Week 48
Number of Participants That Experienced a Potentially Clinically Significant Electrocardiogram Measurements
Time frame: Baseline to Week 48
Number of Participants That Experienced a Potentially Clinically Significant Echocardiogram Measurement
Time frame: Baseline, Week 24 and Week 48
Number of Participants That Experienced a Clinically Significant Haematology Result (Investigator's Assessment)
Time frame: Day 1 to Week 48
Number of Participants Who Experienced a Clinically Significant Biochemistry Result (Investigator's Assessment)
Time frame: Day 1 to Week 48
Number of Participants That Experienced a Potentially Clinically Significant Liver Function Result
Time frame: Baseline to Week 48
Number of Participants That Experienced a Clinically Significant Urinalysis Result (Investigator's Assessment)
Time frame: Day 1 to Week 48
Number of Participants That Experienced a Clinically Significant Coagulation Result (Investigator's Assessment)
Time frame: Day 1 to Week 48

Results and safety

Results posted to the registry on 2 Jan 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort 1: SMT C1100 Formulation 1	30	28
Cohort 2: SMT C1100 Formulation 2	10	9
Cohort 3: SMT C1100 Formulation 1	3	0

Primary outcome: Change From Baseline in Magnetic Resonance Spectroscopy (MRS) Fat Fraction (FF) for Leg Muscles

Time frame: Baseline, Week 12, Week 24, Week 36 and Week 48. Mean (95% Confidence Interval). Unit: Percentage of fat in the muscle

Measure	Cohorts 1 and 2: SMT C1100 n = 40
Vastus Lateralis: Week 12 Change from Baseline	1.779 (0.939 to 2.620)
Vastus Lateralis: Week 24 Change from Baseline	3.914 (2.695 to 5.132)
Vastus Lateralis: Week 36 Change from Baseline	5.238 (3.563 to 6.913)
Vastus Lateralis: Week 48 Change from Baseline	7.142 (4.866 to 9.417)
Soleus: Week 12 Change from Baseline	0.615 (0.068 to 1.162)
Soleus: Week 24 Change from Baseline	1.108 (0.350 to 1.865)
Soleus: Week 36 Change from Baseline	2.384 (1.287 to 3.481)
Soleus: Week 48 Change from Baseline	2.584 (1.258 to 3.909)

Population analysed: All participants who received at least one dose of study medication and had at least one assessment of the endpoint (which could be their baseline assessment).

Primary outcome: Change From Baseline for Magnetic Resonance Spectroscopy (MRS) Water Transverse Relaxation Time (WTRT) for Leg Muscles

Time frame: Baseline, Week 12, Week 24, Week 36 and Week 48. Mean (95% Confidence Interval). Unit: Milliseconds

Measure	Cohorts 1 and 2: SMT C1100 n = 40
Vastus Lateralis: Week 12 Change from Baseline	-0.559 (-1.190 to 0.072)
Vastus Lateralis: Week 24 Change from Baseline	-0.486 (-1.193 to 0.221)
Vastus Lateralis: Week 36 Change from Baseline	-0.849 (-1.454 to -0.244)
Vastus Lateralis: Week 48 Change from Baseline	-0.822 (-1.673 to 0.028)
Soleus: Week 12 Change from Baseline	-0.655 (-1.209 to -0.101)
Soleus: Week 24 Change from Baseline	-0.861 (-1.440 to -0.281)
Soleus: Week 36 Change from Baseline	-0.447 (-1.085 to 0.190)
Soleus: Week 48 Change from Baseline	-0.119 (-0.747 to 0.509)

Population analysed: All participants who received at least one dose of study medication and had at least one assessment of the endpoint (which could be their baseline assessment).

Primary outcome: Observed Trough Plasma Concentration (Ctrough) for SMT C1100, Dihydrodiol 1 (DHD1) and Dihydrodiol III (DHD 3)

Time frame: Pre-dose at Weeks 1, 4, 8, 12, 24, 36 and 48. Geometric mean (Geometric Coefficient of Variation). Unit: ng/mL

Measure	Cohort 1: SMT C1100 Formulation 1 n = 30	Cohort 2: SMT C1100 Formulation 2 n = 10
SMT C1100	17 (140)	80 (83.1)
DHD 1	155 (61)	365 (55)
DHD 3	484 (67)	1206 (68)

Population analysed: All participants in Cohorts 1 or 2 who received at least one dose of study medication and had at least one concentration measurement (which could be below the limit of quantification). No evaluable data was collected from Cohort 3 participants due to early study termination.

Primary outcome: Simulated Maximum Plasma Concentration (Cmax) for SMT C1100, Dihydrodiol 1 (DHD1) and Dihydrodiol III (DHD 3)

Time frame: Pre-dose and 3 to 10 hours post-dose at Weeks 1, 4, 8, 12, 24, 36 and 48. Geometric mean (Full Range). Unit: ng/mL

Measure	Cohort 1: SMT C1100 Formulation 1 n = 30	Cohort 2: SMT C1100 Formulation 2 n = 10
SMT C1100	135 (97 to 185)	415 (303 to 640)
DHD 1	1897 (1690 to 2158)	2829 (2597 to 3072)
DHD 3	3162 (2392 to 4053)	4652 (3802 to 6116)

19 secondary outcomes are reported in the full results.

Adverse events

Time frame: Day 1 to a maximum of 96 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort 1: SMT C1100 Formulation 1	4 of 30 (13.3%)	30 of 30 (100%)	0 of 30
Cohort 2: SMT C1100 Formulation 2	0 of 10 (0%)	10 of 10 (100%)	0 of 10
Cohort 3: SMT C1100 Formulation 1	0 of 3 (0%)	3 of 3 (100%)	0 of 3

Limitations and caveats (from the sponsor): Analysis of the data collected from Cohort 3 was limited as the study was terminated prior to the first participant's Week 24 visit.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 2 Jan 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Monitor study director

Summit (Oxford) Limited

16 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ezutromid in people with Duchenne Muscular Dystrophy, run by Summit Therapeutics at 16 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 2 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Magnetic Resonance Spectroscopy (MRS) Fat Fraction (FF) for Leg Muscles (time frame: Baseline, Week 12, Week 24, Week 36 and Week 48). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02858362.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jan 2020; AzTrials last refreshed its copy on 26 Oct 2026.