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

Sponsor

Santhera Pharmaceuticals (Industry)

Overall Status

Terminated

CT.gov ID

NCT02814019

Collaborator

(none)

255

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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

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

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 Design

Study Type:

Interventional

Actual Enrollment :

255 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (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

Study Start Date :

Sep 1, 2016

Actual Primary Completion Date :

Dec 1, 2020

Actual Study Completion Date :

Dec 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

Change From Baseline in Forced Vital Capacity percent predicted (FVC %p) at Week 78 [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 [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 [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 [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

Eligibility Criteria

Criteria

Ages Eligible for Study:

10 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Inclusion Criteria:

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.
Minimum 10 years old at Screening.
Signed and dated Informed Consent Form.
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.
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).
Ability to provide reliable FVC values at Screening and Baseline, and reproducible within 15% (relative change) at Baseline compared to Screening.
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.
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:

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.
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).
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.
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.
Asthma, bronchitis/COPD, bronchiectasis, emphysema, pneumonia or presence of any other non-DMD respiratory illness that affects respiratory function.
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.
Any bronchopulmonary illness that required treatment with antibiotics within 3 months prior to Screening.
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).
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.
Relevant history of or current drug or alcohol abuse, or use of any tobacco or marijuana products/smoking.
Known individual hypersensitivity to idebenone or to any of the ingredients or excipients of the study medication.
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

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama	Birmingham	Alabama	United States	35233
2	Phoenix Children's Hospital	Phoenix	Arizona	United States	85016
3	Banner University of Arizona Medical Center	Tucson	Arizona	United States	85724
4	Childrens Hospital of Los Angeles	Los Angeles	California	United States	90027
5	David Geffen School of Medicine at UCLA	Los Angeles	California	United States	90095
6	UC Davis Department of Physical Medicine and Rehabilitation	Sacramento	California	United States	95817
7	Loma Linda University Healthcare	San Bernardino	California	United States	92354
8	Shriners Hospitals for Children-Tampa	Tampa	Florida	United States	33612
9	Rare Disease Research	Atlanta	Georgia	United States	30318
10	University of Iowa	Iowa City	Iowa	United States	52242
11	University of Kansas	Fairway	Kansas	United States	66103
12	Johns Hopkins University	Baltimore	Maryland	United States	21287
13	Children's Hospital Boston	Boston	Massachusetts	United States	02115
14	Gillette Children's Specialty Healthcare	Saint Paul	Minnesota	United States	55101
15	University of Rochester Medical Center	Rochester	New York	United States	14642
16	Neurosciences Institute, Neurology - Charlotte Carolinas Healthcare System	Charlotte	North Carolina	United States	28207
17	Cincinnati Children's Hospital	Cincinnati	Ohio	United States	45229-3039
18	MetroHealth Medical Center	Cleveland	Ohio	United States	44109-1988
19	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104-1771
20	Cook Children's Medical Center	Fort Worth	Texas	United States	76087
21	Gottfried von Preyer'sches Kinderspital	Wien		Austria	1100
22	University Hospital Leuven	Leuven		Belgium	3000
23	Centre de Référence Neuromusculaire, CHR Citadelle	Liège		Belgium	4000
24	Sofia Medical University	Sofia		Bulgaria	1431
25	Service de neuropédiatrie Pôle Pédiatrie CHRU de Lille - Hôpital Jeanne de Flandre	Lille		France	59037
26	CHRU de Montpellier - Hôpital Gui de Chauliac	Montpellier		France	34295
27	Hôpital Hôtel Dieu	Nantes		France	44093
28	I-Motion - Plateforme d'essais cliniques pédiatriques Hôpital Armand Trousseau bâtiment Lemariey porte 20	Paris		France
29	Hôpital des enfants	Toulouse		France	31059
30	Universitätsmedizin Berlin Campus Virchow-Klinikum	Berlin		Germany	13353
31	Universitätsklinikum Essen	Essen		Germany	45147
32	Universitätsklinik Freiburg Zentrum für Kinderheilkunde und Jugendmedizin	Freiburg		Germany
33	Universitätsklinikum Hamburg-Eppendorf, Klinik für Kinder- und Jugendmedizin	Hamburg		Germany	20246
34	Universitätsklinikum Heidelberg Zentrum für Kinder- und Jugendmedizin	Heidelberg		Germany
35	Uniklinik Köln	Köln		Germany	50937
36	Zentrum für neuromuskuläre Erkrankungen	München		Germany
37	Semmelweis University 2nd Department of Paediatrics	Budapest		Hungary
38	Children's University Hospital	Dublin		Ireland	1
39	Institute of Neurology at Schneider Children's Medical Center of Israel	Petah Tiqva		Israel	4920235
40	Fondazione IRCCS Eugenio Medea	Bosisio Parini		Italy	23842
41	Istituto Giannina Gaslini	Genova		Italy	16147
42	Scientific Coordinator Nemo Sud Clinical Center	Messina		Italy	98125
43	Centro Clinico NEMO (NEuroMuscular Omnicentre), Niguarda Hospital	Milano		Italy
44	Servizio di Cardiomiologia e Genetica Medica, AOU Università degli Studi della Campania "Luigi Vanvitelli"	Napoli		Italy	80131
45	Reparto Di Neurologia dell'Osperdale Di Padova	Padova		Italy	35122
46	Dipartimento di Clinica Neurologica e Psichiatrica dell'Età Evolutiva della Fondazione IRCCS "C. Mondino" di Pavia	Pavia		Italy	27100
47	U.O.C. Neuropsichiatria Infantile	Roma		Italy	00168
48	LUMC	Leiden		Netherlands
49	Radboud university medical centre	Nijmegen		Netherlands	6500
50	Hospital Sant Joan de Déu Neuropediatra	Barcelona		Spain	08950
51	Hospital Universitari Vall D' Hebron	Barcelona		Spain	8950
52	Hospital Universitario La Paz	Madrid		Spain	28046
53	Hospital Universitario Virgen del Rocio	Sevilla		Spain	41013
54	Hospital La Fe de Valencia	Valencia		Spain	106 46026
55	Sahlgrenska University Hospital	Gothenburg		Sweden
56	Center for neuromuscular disorders, Universitäts-Kinderspital beider Basel (UKBB)	Basel		Switzerland	4301
57	Leeds Teaching Hospital NHS Trust	Leeds		United Kingdom	LS1 3EX
58	UCL, National Hospital for Neurology and Neurosurgery	London		United Kingdom	WC1 3BG
59	Great Ormond Street Hospital for Children	London		United Kingdom	WC1N 3JH
60	John Walton Muscular Dystrophy Research Centre	Newcastle		United Kingdom
61	Robert Jones and Agnes Hunt Orthopaedic Hospital	Oswestry		United Kingdom	SY10 7AG
62	Oxford University hospitals NHS Foundation Trust	Oxford		United Kingdom	OX39DU
63	Royal Hallamshire Hospital	Sheffield		United Kingdom	S10 2JF