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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2017 by Santhera Pharmaceuticals
Sponsor:
Information provided by (Responsible Party):
Santhera Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02814019
First received: June 17, 2016
Last updated: May 17, 2017
Last verified: May 2017
  Purpose
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

Condition Intervention Phase
Duchenne Muscular Dystrophy (DMD)
Drug: Idebenone 150 mg film-coated tablets
Drug: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator, Outcomes Assessor
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Santhera Pharmaceuticals:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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



Estimated Enrollment: 266
Study Start Date: September 2016
Estimated Study Completion Date: August 2019
Estimated Primary Completion Date: July 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: idebenone 150 mg film-coated tablets
900 mg idebenone/day (2 tablets to be taken 3 times a day with meals)
Drug: Idebenone 150 mg film-coated tablets
Placebo Comparator: placebo
matching placebo tablets
Drug: placebo

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 6 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 the SIDEROS-E is terminated or Marketing Authorization is obtained for idebenone in DMD, 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.

  Eligibility

Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male patients with a 30% ≤ FVC ≤ 80% of predicted value at Screening and at Baseline.
  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. 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 adjustment determined by weight changes are allowed).
  6. Ability to provide reliable and reproducible repeat FVC within 15% of the screening assessment at Baseline.
  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 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 Stage C by ACCF/AHA guideline or NYHA 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 US as part of the Expanded Access Program).
  3. Prior or ongoing exon-skipping or read-through therapy for DMD.
  4. Planned or expected spinal fixation surgery during the study period (as judged by the Investigator, i.e. due to rapidly progressing scoliosis), prior spinal fixation 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, anti-cholinergics, 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 (Child-Pugh class B [7 to 9 points] or Child-Pugh class C [10 to 15 points]) or severe renal impairment (eGFR <30 mL/min/1.73 m2).
  9. Prior or ongoing medical condition or laboratory abnormality which 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 (please see below Note).
  10. History of or current drug or alcohol abuse or use of any tobacco/marijuana products/smoking.
  11. Known individual hypersensitivity to idebenone or to any of the ingredients/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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02814019

Contacts
Contact: Jodi Wolff sideros@santhera.com

  Show 63 Study Locations
Sponsors and Collaborators
Santhera Pharmaceuticals
  More Information

Additional Information:
Publications:
Responsible Party: Santhera Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02814019     History of Changes
Other Study ID Numbers: SNT-III-012
Study First Received: June 17, 2016
Last Updated: May 17, 2017

Keywords provided by Santhera Pharmaceuticals:
respiratory function in DMD

Additional relevant MeSH terms:
Muscular Dystrophies
Muscular Dystrophy, Duchenne
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Idebenone
Ubiquinone
Glucocorticoids
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Micronutrients
Growth Substances
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on May 24, 2017