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A Phase III Double-blind Study With Idebenone in Patients With Duchenne Muscular Dystrophy (DMD) Taking Glucocorticoid Steroids (SIDEROS)

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ClinicalTrials.gov Identifier: NCT02814019
Recruitment Status : Recruiting
First Posted : June 27, 2016
Last Update Posted : April 15, 2019
Sponsor:
Information provided by (Responsible Party):
Santhera Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE June 17, 2016
First Posted Date  ICMJE June 27, 2016
Last Update Posted Date April 15, 2019
Study Start Date  ICMJE September 2016
Estimated Primary Completion Date August 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 27, 2016)
Change From Baseline in Forced Vital Capacity percent predicted (FVC %p) at Week 78 [ Time Frame: 78 weeks ]
Delaying the loss of respiratory function in patients with DMD receiving glucocorticoid steroids as measured by changes in FVC %p from Baseline to Week 78 using hospital based spirometry.
Original Primary Outcome Measures  ICMJE
 (submitted: June 22, 2016)
Delaying the loss of respiratory function [ Time Frame: 78 weeks ]
Delaying the loss of respiratory function in patients with DMD receiving glucocorticoid steroids as measured by changes in Forced Vital Capacity percent predicted (FVC %p) from Baseline to Week 78 using hospital based spirometry.
Change History Complete list of historical versions of study NCT02814019 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 27, 2016)
  • Change From Baseline in Percent Predicted Peak Expiratory Flow (PEF %p) at Week 78 [ Time Frame: 78 weeks ]
    Delaying the loss of respiratory function in patients with DMD receiving glucocorticoid steroids as measured by: •The change from Baseline to Week 78 in PEF %p assessed by hospital-based spirometry measurements
  • Change From Baseline in Forced Vital Capacity (FVC) at Week 78 [ Time Frame: 78 weeks ]
    Delaying the loss of respiratory function in patients with DMD receiving glucocorticoid steroids as measured by: •The time to first 10% decline in FVC (L) during the 78-week treatment period, assessed by hospital-based spirometry measurements
  • Change from Baseline in Inspiratory Flow Reserve (IFR) at Week 78 [ Time Frame: 78 weeks ]
    Delaying the loss of respiratory function in patients with DMD receiving glucocorticoid steroids as measured by: •The change from Baseline to Week 78 in IFR assessed by hospital-based spirometry measurements
Original Secondary Outcome Measures  ICMJE
 (submitted: June 22, 2016)
  • Delaying the loss of respiratory function [ Time Frame: 78 weeks ]
    Delaying the loss of respiratory function in patients with DMD receiving glucocorticoid steroids as measured by: •The change from Baseline to Week 78 in PEF %p assessed by hospital-based spirometry measurements
  • Delaying the loss of respiratory function [ Time Frame: 78 weeks ]
    Delaying the loss of respiratory function in patients with DMD receiving glucocorticoid steroids as measured by: •The time to first 10% decline in FVC (L) during the 78-week treatment period, assessed by hospital-based spirometry measurements
  • Delaying the loss of respiratory function [ Time Frame: 78 weeks ]
    Delaying the loss of respiratory function in patients with DMD receiving glucocorticoid steroids as measured by: •The change from Baseline to Week 78 in Inspiratory Flow Reserve (IFR) assessed by hospital-based spirometry measurements
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase III Double-blind Study With Idebenone in Patients With Duchenne Muscular Dystrophy (DMD) Taking Glucocorticoid Steroids
Official Title  ICMJE A Phase III Double-blind, Randomized, Placebo-Controlled Study Assessing the Efficacy, Safety and Tolerability of Idebenone in Patients With Duchenne Muscular Dystrophy Receiving Glucocorticoid Steroids
Brief Summary The purpose of the study is to assess the efficacy of idebenone in delaying the loss of respiratory function in patients with DMD receiving concomitant glucocorticoid steroids
Detailed Description

The SIDEROS trial is a randomized, placebo controlled, parallel group study of the efficacy of idebenone in delaying the loss of respiratory function, whilst also monitoring safety and tolerability of idebenone in at least 266 DMD patients taking stable dose of concomitant glucocorticoid steroids.

The study treatment period will be 18 months/ 78 weeks and the idebenone dose will be 900 mg/day. Participants can use deflazacort or prednisolone and be on any dose regimen.

Since glucocorticoid steroids are widely used in ambulant boys from an early age until late into teenage and even adult years, this study will not take age and ambulatory status into account and will only exclude patients that need daytime ventilator assistance.

The schedule of assessments will include a Screening Visit and up to 9 protocol visits, including a Follow-up Visit.

A Screening Visit will take place a maximum of 4 weeks prior to the Baseline Visit (Visit 1, study day -1). Beginning at Baseline, the patient will receive study medication to be taken at home, and will undergo regular assessments in the clinic throughout the study period until Visit 8 at Week 78 at which time the study will be completed and medication discontinued.

All patients completing Visit 8/Week 78, and considered eligible by the Investigator will be able to participate in an open-label extension study (SIDEROS-E) and will continue to receive idebenone until idebenone is commercially available for patients included in the study or SIDEROS-E is terminated by the Sponsor, whichever occurs first. The duration of the SIDEROS-E study will be defined in a separate protocol.

For all patients not participating in the extension study (SIDEROS-E), a Follow-up Visit (Visit 9/Follow-up Visit) will take place 4 weeks after end of Treatment at Visit 8/Week 78 or after premature discontinuation of study medication.

Each hospital visit will include efficacy assessments (respiratory function assessed by hospital-based spirometry, oxygen saturation, end-tidal CO2) and safety assessments (adverse events, concomitant medication, physical examination, vital signs, safety laboratory evaluations). In addition, respiratory function will be assessed weekly at home with a hand-held device in order to closely monitor respiratory function between hospital visits.

The study medication, all medical procedures and laboratory testing, and the visits to the study centre are free of charge. In addition the patients will receive a travel allowance to cover reasonable expenses to and from the study centre. Participants will not otherwise be compensated for this study.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Duchenne Muscular Dystrophy (DMD)
Intervention  ICMJE
  • Drug: Idebenone 150 mg film-coated tablets
  • Drug: placebo
Study Arms  ICMJE
  • Experimental: idebenone 150 mg film-coated tablets
    900 mg idebenone/day (2 tablets to be taken 3 times a day with meals)
    Intervention: Drug: Idebenone 150 mg film-coated tablets
  • Placebo Comparator: placebo
    matching placebo tablets
    Intervention: Drug: placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 22, 2016)
266
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 2021
Estimated Primary Completion Date August 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male patients with a 35% ≤ FVC ≤ 80% of predicted value at Screening and at Baseline and who, in the opinion of the investigator are in the respiratory function decline phase.
  2. Minimum 10 years old at Screening.
  3. Signed and dated Informed Consent Form.
  4. Documented diagnosis of DMD (severe dystrophinopathy) and clinical features consistent of typical DMD at diagnosis (i.e. documented delayed motor skills and muscle weakness by age 5 years). DMD should be confirmed by mutation analysis in the dystrophin gene or by substantially reduced levels of dystrophin protein (i.e. absent or <5% of normal) on Western blot or immunostaining.
  5. Chronic use of systemic glucocorticoid steroids for DMD related conditions continuously for at least 12 months prior to Baseline without any dose adjustments on a mg/kg basis in the last 6 months (only dose adjustments determined by weight changes are allowed).
  6. Ability to provide reliable FVC values at Screening and Baseline, and reproducible within 15% (relative change) at Baseline compared to Screening.
  7. Patients assessed by the Investigator as willing and able to comply with the requirements of the study, possess the required cognitive abilities and are able to swallow study medication.
  8. Patients who prior to Screening have been immunized with 23-valent pneumococcal polysaccharide vaccine or any other pneumococcal polysaccharide vaccine as per national recommendations, as well as annually immunized with inactivated influenza vaccine.

Exclusion Criteria:

  1. Symptomatic heart failure (defined as patients with structural heart disease, dyspnea, fatigue and impaired tolerance to exercise; Stage C by the ACCF/AHA guideline or NYHA Classes III-IV) and/or symptomatic ventricular arrhythmias.
  2. Ongoing participation in any other therapeutic trial and/or intake of any investigational drug within 90 days prior to Baseline (only exception allowed is use of Deflazacort in the US as part of the Expanded Access Program, or any approved corticosteroid product in trial for regimen optimization, for which the patient met the inclusion criterion 5).
  3. Ongoing exon-skipping therapy or read-through gene therapy for DMD; previous exon-skipping or read-through gene therapy is allowed if the stop date was more than 6 months prior to Screening.
  4. Planned or expected spinal fusion surgery during the study period (as judged by the Investigator; i.e. due to rapidly progressing scoliosis), previous spinal fusion surgery is allowed if it took place more than 6 months prior to Screening.
  5. Asthma, bronchitis/COPD, bronchiectasis, emphysema, pneumonia or presence of any other non-DMD respiratory illness that affects respiratory function.
  6. Chronic use of beta2-agonists or any use of other bronchodilating/bronchoconstricting medication (inhaled steroids, sympathomimetics, anticholinergics, antihistamines); chronic use is defined as a daily intake for more than 14 days.
  7. Any bronchopulmonary illness that required treatment with antibiotics within 3 months prior to Screening.
  8. Moderate or severe hepatic impairment (use as guidance Child-Pugh class B [7 to 9 points] or Child-Pugh class C [10 to 15 points] - see Appendix B) or severe renal impairment (eGFR <30 mL/min/1.73 m2).
  9. Prior or ongoing medical condition or laboratory abnormality that in the Investigator's opinion may put the patient at significant risk may confound the study results or may interfere significantly with the patient's participation in the study.
  10. Relevant history of or current drug or alcohol abuse, or use of any tobacco or marijuana products/smoking.
  11. Known individual hypersensitivity to idebenone or to any of the ingredients or excipients of the study medication.
  12. Daytime ventilator assistance (defined as use of any assisted ventilation while awake).

Note: Patients who suffer from a severe, unstable condition including (but not limited to) cancer, auto-immune diseases, hematological diseases, metabolic disorders or immunodeficiencies, and who are at risk of an aggravation unrelated to the study condition, can only be included in the study if accepted in writing by the Sponsor's Senior Clinical Research Physician.

Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 10 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jodi Wolff sideros@santhera.com
Listed Location Countries  ICMJE Austria,   Belgium,   Bulgaria,   France,   Germany,   Hungary,   Ireland,   Israel,   Italy,   Netherlands,   Spain,   Sweden,   Switzerland,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02814019
Other Study ID Numbers  ICMJE SNT-III-012
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Santhera Pharmaceuticals
Study Sponsor  ICMJE Santhera Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Santhera Pharmaceuticals
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP