A clinical trial to test how the study medication (SMT C1100) works and how safe it is when given to children with Duchenne Muscular Dystrophy

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2015-004333-27-GB
• Date of registration: 04/11/2015
• Prospective Registration: Yes
• Primary sponsor: Summit (Oxford) Limited
• Public title: A clinical trial to test how the study medication (SMT C1100) works and how safe it is when given to children with Duchenne Muscular Dystrophy
• Scientific title: A Phase 2 Clinical Study to Assess the Activity and Safety of Utrophin Modulation with SMT C1100 in Ambulatory Paediatric Male Subjects with Duchenne Muscular Dystrophy (C11005) - PoC Study to Assess Activity and Safety of SMT C1100 in Boys with DMD
• Date of first enrolment: 19/01/2016
• Target sample size: 40
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-004333-27
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

United Kingdom, United States

Contacts

• Name: Clinical Trial Information
• Affiliation: Summit (Oxford) Limited

• Name: Clinical Trial Information
• Affiliation: Summit (Oxford) Limited

Key inclusion & exclusion criteria

Inclusion criteria:
Patients will be required to satisfy the following criteria at the screening visit:
1. Be able to provide written informed consent/assent as per local requirements.
2. Be male.
3.Be aged =5 years <10 years of age (from 5th birthday to 10th birthday)-not applicable for cohort 3
4. 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.
5. Have prior confirmation of the 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 organization. Or Documentation of the absence of dystrophin in the muscle (via biopsy).
6. Be willing and able to comply with two muscle biopsy procedures (not applicable for cohort 3)
7. Be able to undergo MRI examination.
8. Patients 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.
9. Have the ability to walk at least 300 meters unassisted during the screening 6MWD and be below the protocol-specified threshold for 80%-predicted 6MWD (not applicable for cohort 3)
10. Have results of two 6MWD at Baseline determined as valid. The results of the second 6MWD must be within 20% of the first 6MWD (not applicable for cohort 3)
11. Have cardiac ECHO measurements showing an ejection fraction of = 55% and fractional shortening of =28% (not applicable for cohort 3)
12. 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 (e.g., aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase and creatinine phosphokinase) classed by the Investigator as not clinically significant will not exclude the patient
13. Be willing and able to comply with scheduled visits, drug administration plan, study procedures, laboratory tests and study restrictions.
14.Have taken part in a prior SMT C1100 study (not applicable for cohorts 1 and 2 )
Are the trial subjects under 18? yes
Number of subjects for this age range: 40
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Patients will be excluded from the study if they satisfy the following
criteria at the screening visit
1. Have physical exam findings that in the investigator’s opinion should be exclusionary e.g., lower limb injury that may affect 6MWD performance.
2. 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.
3. Have uncontrolled clinical symptoms and signs of CHF (American College of Cardiology/American Heart Association Stage C or Stage D).
4.Have abnormal GLDH at baseline (>1.5 x ULN)
5.Have abnormal coagulation times at baseline (>1.5 x ULN)
6. Have an abnormal ECG e.g., a QTcF >500ms, left bundle-branch block or any other major conduction defect.
7. Use beta blockers (however, if during the course of the study they are clinically indicated they can be initiated; not applicable for cohort 3 )
8. Use herbal supplements and be unwilling to stop these for the duration of the study.
9. Have a known hypersensitivity to any of the ingredients or excipients of the IMP. (microfluidised oral suspension F3, cohort 1 : Poloxamer 188, Methylparaben, Propylparaben, Hydroxypropylmethyl cellulose, Glycerol, Non crystallizing sorbitol [70%], Xanthan gum, Strawberry cream flavour [PHS-132963]);
10.Have a known hypersensitivity to any of the ingredients or excipients of the IMP. Powder for oral suspension (F6): hypromellose acetate (not applicable to cohorts 1 and 3 )
11. 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 (e.g FOR-DMD or ACCESS DMD clinical trials ) within this period would not exclude the patient (provided they have been on stable treatment for 6 months )
12. Have a history of major surgical procedure within 12 weeks prior to the start of the Treatment Phase (week 1)
13. Be undertaking ongoing immunosuppressive therapy (other than corticosteroids).
14. Have an expectation of a major surgical procedure (e.g., scoliosis surgery) during the 12-month Treatment Phase of the study.
15. Require daytime ventilator assistance.
16. Have a prior or ongoing medical condition (e.g., concomitant illness, psychiatric condition, behavioural disorder, alcoholism, drug abuse), medical history, ECG findings, or laboratory abnormality that, in the Investigator's opinion, could adversely affect the safety of the subject, makes it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of study results.
17. Be dairy or lactose intolerant or have any other dietary restrictions that might interfere with the conduct of the study.
18. Be a smoker, use other tobacco or nicotine products or be exposed to daily passive smoking (including parent/legal guardian, siblings) so as to minimize environmental factors causing CYP1A induction.
19.Be using an approved DMD medication or anticipates using one during the duration of t

Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Duchenne Muscular Dystrophy
MedDRA version: 20.0 Level: PT Classification code 10013801 Term: Duchenne muscular dystrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Product Code: SMT C1100
Pharmaceutical Form: Oral suspension
INN or Proposed INN: Pending
CAS Number: 945531-77-1
Current Sponsor code: SMT C1100
Concentration unit: mg/g milligram(s)/gram
Concentration type: equal
Concentration number: 200-

Primary Outcome(s)

Primary end point(s): Change from baseline to Weeks 12, 24, 36 and 48 in MRI leg muscles parameters(Cohorts 1 and 2)

SMT C1100 and metabolite plasma concentrations at Weeks 1 (Days 1 and 7) as applicable (Cohorts 2 and 3 only) 4, 8 (Cohorts 1 and 2 only), 12, 24, 36 and 48

• Safety data including:
Treatment emergent AEs

Timepoint(s) of evaluation of this end point: From baseline to Weeks 12, 24, 36 and 48

Main Objective: To investigate changes in leg MRI in paediatric patients with DMD, following treatment with SMT C1100(cohorts 1 and 2 )

To investigate the relationships between changes in leg MRI with plasma concentrations of SMT C1100 and its metabolites in paediatric patients with DMD, following treatment with SMT C1100 (cohorts 1 and 2)

To assess the safety and tolerability of SMT C1100 and its metabolites in paediatric patients with DMD

Secondary Objective: To investigate changes in utrophin expression and muscle fibre regeneration in muscle, in paediatric patients with DMD, following treatment with SMT C1100 (cohorts 1 and 2 )
To investigate the relationships between changes , utrophin expression and fibre regeneration in muscle and safety parameters with plasma concentrations of SMT C1100 and its metabolites in paediatric patients with DMD, following treatment with SMT C1100 (cohorts 1 and 2 )
To investigate changes in pulmonary function tests in paediatric subjects with DMD, following treatment with SMT C1100
To investigate the relationships between changes in pulmonary function tests with plasma concentrations of SMT C1100 and its metabolites in paediatric subjects with DMD, following treatment with SMT C1100

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: From baseline to Week 24 or 48

Secondary end point(s): Change from baseline to Week 24 or 48 in utrophin expression via muscle biopsy analysis (Cohorts 1 and 2)
• Change from baseline to Week 24 or 48 in muscle regeneration biomarkers, via muscle biopsy analysis(Cohorts 1 and 2)
• Change from baseline to Weeks 12, 24, 36 and 48 (Cohorts 1 and 2) and from baseline to Weeks 1, 24 and 48 (Cohort 3) in pulmonary function tests
• Safety data including:
• Vital signs (systolic and diastolic blood pressure and heart rate)
• Physical examination
• Twelve-lead electrocardiogram (ECG)
• Echocardiogram (ECHO)
• Pulmonary function tests (forced expiratory volume in 1 second [FEV1], forced vital capacity [FVC] maximum inspiratory pressure [MIP], maximum expiratory pressure [MEP] and peak expiratory flow [PEF]);Peak cough flow (PCF) (Cohort 3)Sniff nasal inspiratory pressure (SNIP) (Cohort 3

• Safety laboratory evaluations (clinical chemistry, haematology (all 3 cohorts) coagulation (Cohort 2 and Cohort 3) parameters and urinalysis (all 3 cohorts)

Secondary ID(s)

SMTC11005

Source(s) of Monetary Support

Summit (Oxford) Limited

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 25/10/2018
• Date Completed: 11/09/2018
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2015-004333-27/results