Idebenone for Primary Progressive Multiple Sclerosis

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ClinicalTrials.gov Identifier: NCT01854359

Recruitment Status : Completed

First Posted : May 15, 2013

Results First Posted : May 19, 2021

Last Update Posted : May 19, 2021

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Sponsor:

Information provided by (Responsible Party):

National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

Study Type	Interventional
Study Design	Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Conditions	Multiple Sclerosis Primary Progressive Multiple Sclerosis
Intervention	Drug: Idebenone
Enrollment	61

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Active Treatment in 09-I-0197	Placebo in 09-I-0197
Arm/Group Description	Idebenone (150mg tablets) administe...	Idebenone (150mg tablets) administe...
Arm/Group Description	Idebenone (150mg tablets) administered orally as five tablets, three times per day with food. This group completed a total of 3 years of Idebenone treatment	Idebenone (150mg tablets) administered orally as five tablets, three times per day with food. This group completed a total of 1 year of Idebenone treatment (following 2 years of placebo treatment in the 09-I-0198 trial).
Period Title: Overall Study
Started	31	30
Completed	26	22
Not Completed	5	8

Baseline Characteristics

Arm/Group Title		Active Treatment in 09-I-0197	Placebo in 09-I-0197	Total
Arm/Group Description		Idebenone (150mg tablets) administe...	Idebenone (150mg tablets) administe...	Total of all reporting groups
Arm/Group Description		Idebenone (150mg tablets) administered orally as five tablets, three times per day with food. This group completed a total of 3 years of Idebenone treatment.	Idebenone (150mg tablets) administered orally as five tablets, three times per day with food. This group completed a total of 1 year of Idebenone treatment (following 2 years of placebo treatment in the 09-I-0197 trial)	Total of all reporting groups
Overall Number of Baseline Participants		31	30	61
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	31 participants	30 participants	61 participants
		60.0 (6.7)	59.2 (7.2)	59.6 (6.9)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	31 participants	30 participants	61 participants
	Female	14 45.2%	17 56.7%	31 50.8%
	Male	17 54.8%	13 43.3%	30 49.2%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	31 participants	30 participants	61 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	3 9.7%	3 10.0%	6 9.8%
	White	28 90.3%	27 90.0%	55 90.2%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%

Outcome Measures

1.Primary Outcome


Title	Area Under the Curve (AUC) of the Combinatorial Weight-Adjusted Disability Score (CombiWISE)
Description	CombiWISE is a composite scale derived from Expanded Disability Status...
Description	CombiWISE is a composite scale derived from Expanded Disability Status Scale (EDSS) , Scripps Neurological Disability Scale (SNRS), times 25 foot walk (25FW), and non-dominant hand of 9 hole peg test (9HPT) with a minimum value of 0 (no disability) and maximum value of 100 (maximum disability). The AUC values were calculated for both study groups (Active treatment group in the 09-I-0197 trial and Placebo group in the 09-I-0197) as follows: pre-treatment baseline during the 09-I-0197 trial (from Months -12, -6, and 0) double-blind phase during the 09-I-0197 trial (from Months 0, 6, 12, 18, and 24) extension phase during the 13-I-0088 trial (from Months 24, 30, and 36) Because the follow-up times varied from patient to patient, the AUC values were made comparable by scaling them by dividing the AUC value by the square of the actual duration (in years) of each of the phases.
Time Frame	1-year pre-treatment baseline vs 2-year randomized double-blind phased vs 1-year treatment period

Outcome Measure Data

Analysis Population Description

61 subjects that completed three year 09-I-0197 trial enrolled into the one year open-label extension phase of the 13-I-0088.

Out of the 61 subjects, 31 were assigned to the active treatment group in the 09-I-0197 trial and 30 received placebo.

The 09-I-1097 consisted of one-year pre-treatment baseline and 2 years of double-blind treatment phase.


Arm/Group Title	Pre-treatment Baseline (Placebo Group)	Double-blind Phase (Placebo Group)	Extension Phase (Placebo Group)	Pre-treatment Baseline (Active Treatment Group)	Double-blind Phase (Active Treatment Group)	Extension Phase (Active Treatment Group)
Arm/Group Description:	One Year Pre-treatment baseline of ...	Two-Year Double-blind Phase of 09-I...	One-year open label active treatmen...	One Year Pre-treatment baseline of ...	Two-Year Double-blind Phase of 09-I...	One-year open label active treatmen...
Arm/Group Description:	One Year Pre-treatment baseline of the 09-I-0197 trial for placebo group	Two-Year Double-blind Phase of 09-I-0197 (placebo group)	One-year open label active treatment group that received placebo in the 09-I-0197 trial	One Year Pre-treatment baseline of the 09-I-0197 trial for active treatment group	Two-Year Double-blind Phase of 09-I-0197 (active treatment group)	One-year open label active treatment group that received active treatment in the 09-I-0197 trial
Overall Number of Participants Analyzed	30	30	22	31	31	26
Mean (Standard Deviation) Unit of Measure: units on a scale * year
	1.55 (2.02)	0.80 (1.96)	0.46 (1.93)	0.89 (1.81)	0.75 (1.82)	1.30 (2.30)

2.Secondary Outcome


Title	Slopes of 25 Foot Walk (25FW) Time
Description	slopes of measured times of 25FW during the 3-year 09-I-0197 trial (on...
Description	slopes of measured times of 25FW during the 3-year 09-I-0197 trial (one year of pre-treatment baseline and two years of double-blind randomized treatment) and during one year extension phase of the 13-I-0088 trial. The slopes were measured separately for placebo and active treatment arm as randomized in the the 09-I-0197 trial. Lower extremity disability was measured by an average of two trials of timed 25 foot walk assessed every 6 month. The maximum time assigned for a trial is 180s. Patients unable to complete the 25 foot trial within this time limit are coded as "179.9"
Time Frame	3-years double-blind phase and 1-year extension phase

Outcome Measure Data

Analysis Population Description

61 subjects that completed three year 09-I-0197 trial enrolled into the one year open-label extension phase of the 13-I-0088.

Out of the 61 subjects, 31 were assigned to the active treatment group in the 09-I-0197 trial and 30 received placebo.

The 09-I-1097 consisted of one-year pre-treatment baseline and 2 years of double-blind treatment phase.


Arm/Group Title	Placebo Arm of the 09-I-0197	Extension Phase (Placebo Arm)	Active Treatment Arm of the 09-I-0197	Extension Phase (Active Treatment Arm)
Arm/Group Description:	placebo arm of the 09-I-0197 - one ...	One-year open label extension phase...	active treatment arm of the 09-I-01...	One-year open label extension phase...
Arm/Group Description:	placebo arm of the 09-I-0197 - one year pre-treatment baseline plus two years of placebo during the double-blind phase of 09-I-0197	One-year open label extension phase of the 09-I-0917 placebo arm	active treatment arm of the 09-I-0197 - one year pre-treatment baseline plus two years of Idebenone treatment during the double-blind phase of 09-I-0197	One-year open label extension phase of the 09-I-0917 active treatment arm
Overall Number of Participants Analyzed	30	22	31	26
Mean (Standard Error) Unit of Measure: seconds per year
	0.04322 (0.009617)	-0.00531 (0.01599)	0.04031 (0.0106)	0.03401 (0.01286)

3.Secondary Outcome


Title	Slopes of 9 Hole Peg Test (9HPT) Time
Description	Slopes of measured times of 9HPT during the 3-year 09-I-0197 trial (on...
Description	Slopes of measured times of 9HPT during the 3-year 09-I-0197 trial (one year of pre-treatment baseline and two years of double-blind randomized treatment) and during one year extension phase of the 13-I-0088 trial. The slopes were measured separately for placebo and active treatment arm as randomized in the the 09-I-0197 trial. Upper extremity/fine motor movements disability was measured as an average of left and right hand time, with each hand assessed as an average of two trials with upper limit of 5 (300s) per trial. Patients unable to complete the task within this time are coded as "777" The outcome was assessed every 6 months.
Time Frame	3-years double-blind phase and 1-year extension phase

Outcome Measure Data

Analysis Population Description

61 subjects that completed three year 09-I-0197 trial enrolled into the one year open-label extension phase of the 13-I-0088.

Out of the 61 subjects, 31 were assigned to the active treatment group in the 09-I-0197 trial and 30 received placebo.

The 09-I-1097 consisted of one-year pre-treatment baseline and 2 years of double-blind treatment phase.


Arm/Group Title	Placebo Arm of the 09-I-0197	Extension Phase (Placebo Arm)	Active Treatment Arm of the 09-I-0197	Extension Phase (Active Treatment Arm)
Arm/Group Description:	placebo arm of the 09-I-0197 - one ...	One-year open label extension phase...	active treatment arm of the 09-I-01...	One-year open label extension phase...
Arm/Group Description:	placebo arm of the 09-I-0197 - one year pre-treatment baseline plus two years of placebo during the double-blind phase of 09-I-0197	One-year open label extension phase of the 09-I-0917 placebo arm	active treatment arm of the 09-I-0197 - one year pre-treatment baseline plus two years of Idebenone treatment during the double-blind phase of 09-I-0197	One-year open label extension phase of the 09-I-0917 active treatment arm
Overall Number of Participants Analyzed	30	22	31	26
Mean (Standard Error) Unit of Measure: seconds per year
	0.000665 (0.000491)	0.000947 (0.001189)	0.000718 (0.000462)	0.001086 (0.000614)

4.Secondary Outcome


Title	Slopes of Expanded Disability Status Scale (EDSS) Score
Description	Slopes of measured EDSS scores during the 3-year 09-I-0197 trial (one ...
Description	Slopes of measured EDSS scores during the 3-year 09-I-0197 trial (one year of pre-treatment baseline and two years of double-blind randomized treatment) and during one year extension phase of the 13-I-0088 trial. The slopes were measured separately for placebo and active treatment arm as randomized in the the 09-I-0197 trial. EDSS scale combines various elements of neurological exam. EDSS is a discrete scale ranging from 0 to 10 with 0.5 point increments. EDSS of 0 means no neurological disability, while EDSS of 10 marks death due to Multiple Sclerosis (MS). EDSS was assessed every 6 months.
Time Frame	3-years double-blind phase and 1-year extension phase

Outcome Measure Data

Analysis Population Description

61 subjects that completed three year 09-I-0197 trial enrolled into the one year open-label extension phase of the 13-I-0088.

Out of the 61 subjects, 31 were assigned to the active treatment group in the 09-I-0197 trial and 30 received placebo.

The 09-I-1097 consisted of one-year pre-treatment baseline and 2 years of double-blind treatment phase.


Arm/Group Title	Placebo Arm of the 09-I-0197	Extension Phase (Placebo Arm)	Active Treatment Arm of the 09-I-0197	Extension Phase (Active Treatment Arm)
Arm/Group Description:	placebo arm of the 09-I-0197 - one ...	One-year open label extension phase...	active treatment arm of the 09-I-01...	One-year open label extension phase...
Arm/Group Description:	placebo arm of the 09-I-0197 - one year pre-treatment baseline plus two years of placebo during the double-blind phase of 09-I-0197	One-year open label extension phase of the 09-I-0917 placebo arm	active treatment arm of the 09-I-0197 - one year pre-treatment baseline plus two years of Idebenone treatment during the double-blind phase of 09-I-0197	One-year open label extension phase of the 09-I-0917 active treatment arm
Overall Number of Participants Analyzed	30	22	31	26
Mean (Standard Error) Unit of Measure: score on a scale per year
	0.1447 (0.05778)	0.1435 (0.07625)	0.1107 (0.03651)	0.1584 (0.09479)

5.Secondary Outcome


Title	Change in Slopes of Scripps Neurological Rating Scale (SNRS) Score
Description	Slopes of measured SNRS scores during the 3-year 09-I-0197 trial (one ...
Description	Slopes of measured SNRS scores during the 3-year 09-I-0197 trial (one year of pre-treatment baseline and two years of double-blind randomized treatment) and during one year extension phase of the 13-I-0088 trial. The slopes were measured separately for placebo and active treatment arm as randomized in the the 09-I-0197 trial. SNRS scale combines various elements of a neurological exam into a single number. The scale ranges from 100 to 0, where 100 marks no disability and 0 marks maximum disability. SNRS was assessed every 6 months.
Time Frame	3-years double-blind phase and 1-year extension phase

Outcome Measure Data

Analysis Population Description

61 subjects that completed three year 09-I-0197 trial enrolled into the one year open-label extension phase of the 13-I-0088.

Out of the 61 subjects, 31 were assigned to the active treatment group in the 09-I-0197 trial and 30 received placebo. The 09-I-1097 consisted of one-year pre-treatment baseline and 2 years of double-blind treatment phase.


Arm/Group Title	Placebo Arm of the 09-I-0197	Extension Phase (Placebo Arm)	Active Treatment Arm of the 09-I-0197	Extension Phase (Active Treatment Arm)
Arm/Group Description:	placebo arm of the 09-I-0197 - one ...	One-year open label extension phase...	active treatment arm of the 09-I-01...	One-year open label extension phase...
Arm/Group Description:	placebo arm of the 09-I-0197 - one year pre-treatment baseline plus two years of placebo during the double-blind phase of 09-I-0197	One-year open label extension phase of the 09-I-0917 placebo arm	active treatment arm of the 09-I-0197 - one year pre-treatment baseline plus two years of Idebenone treatment during the double-blind phase of 09-I-0197	One-year open label extension phase of the 09-I-0917 active treatment arm
Overall Number of Participants Analyzed	30	22	31	26
Mean (Standard Error) Unit of Measure: score on a scale per year
	-1.8838 (0.4829)	-2.1655 (1.0735)	-2.009 (0.3789)	-2.7263 (1.0073)

Adverse Events

Time Frame	1 year
Adverse Event Reporting Description	Adverse events are collected on 61 patients enrolled in the 1-year open-label phase

Arm/Group Title	Active Treatment in 09-I-0197		Placebo in 09-I-0197
Arm/Group Description	Idebenone (150mg tablets) administe...		Idebenone (150mg tablets) administe...
Arm/Group Description	Idebenone (150mg tablets) administered orally as five tablets, three times per day with food. Two years of Idebenone treatment during the 09-I-0197 double-blind phase		Idebenone (150mg tablets) administered orally as five tablets, three times per day with food. Two years of placebo during the 09-I-0197 double-blind phase
All-Cause Mortality
	Active Treatment in 09-I-0197		Placebo in 09-I-0197
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/31 (0.00%)		0/30 (0.00%)
Serious Adverse Events Serious Adverse Events
	Active Treatment in 09-I-0197		Placebo in 09-I-0197
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/31 (12.90%)		4/30 (13.33%)
Blood and lymphatic system disorders
Elevated liver enzynes ^†	0/31 (0.00%)	0	1/30 (3.33%)	1
Cardiac disorders
Myocardial infarction ^†	1/31 (3.23%)	1	0/30 (0.00%)	0
decreased ejection fraction ^†	1/31 (3.23%)	1	0/30 (0.00%)	0
chest tightness ^†	1/31 (3.23%)	1	0/30 (0.00%)	0
Gastrointestinal disorders
stomach cancer ^†	0/31 (0.00%)	0	1/30 (3.33%)	1
severe constipation ^†	0/31 (0.00%)	0	1/30 (3.33%)	1
Hepatobiliary disorders
gallstones ^†	1/31 (3.23%)	1	0/30 (0.00%)	0
Infections and infestations
ruptured apendix ^†	0/31 (0.00%)	0	1/30 (3.33%)	1
Injury, poisoning and procedural complications
broken ribs ^†	1/31 (3.23%)	1	0/30 (0.00%)	0
broken femur ^†	1/31 (3.23%)	1	0/30 (0.00%)	0
† Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Active Treatment in 09-I-0197		Placebo in 09-I-0197
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/31 (32.26%)		14/30 (46.67%)
Cardiac disorders
chest pain ^†	1/31 (3.23%)	2	0/30 (0.00%)	0
hypertension ^†	1/31 (3.23%)	1	0/30 (0.00%)	0
Endocrine disorders
benign thyroid nodule ^†	0/31 (0.00%)	0	1/30 (3.33%)	1
Eye disorders
retinal detachment ^†	0/31 (0.00%)	0	1/30 (3.33%)	1
transient graying of vision ^†	1/31 (3.23%)	1	0/30 (0.00%)	0
Gastrointestinal disorders
diarrhea ^†	0/31 (0.00%)	0	2/30 (6.67%)	2
nausea ^†	0/31 (0.00%)	0	1/30 (3.33%)	1
General disorders
increased mobility problems ^†	0/31 (0.00%)	0	1/30 (3.33%)	1
Infections and infestations
H1N1 influenza ^†	0/31 (0.00%)	0	1/30 (3.33%)	1
penumonia ^†	1/31 (3.23%)	1	0/30 (0.00%)	0
urinary tract infection ^†	2/31 (6.45%)	2	3/30 (10.00%)	3
Injury, poisoning and procedural complications
fall ^†	1/31 (3.23%)	2	6/30 (20.00%)	7
fractured bone ^†	3/31 (9.68%)	3	0/30 (0.00%)	0
injured meniscus ^†	0/31 (0.00%)	0	2/30 (6.67%)	2
Metabolism and nutrition disorders
dehydration ^†	1/31 (3.23%)	1	0/30 (0.00%)	0
Musculoskeletal and connective tissue disorders
back pain ^†	2/31 (6.45%)	2	0/30 (0.00%)	0
edema ^†	0/31 (0.00%)	0	1/30 (3.33%)	1
radiculopathy ^†	0/31 (0.00%)	0	1/30 (3.33%)	1
Skin and subcutaneous tissue disorders
basal cell carcinoma ^†	0/31 (0.00%)	0	1/30 (3.33%)	1
cellulitis ^†	1/31 (3.23%)	1	0/30 (0.00%)	0
hair loss ^†	1/31 (3.23%)	1	0/30 (0.00%)	0
skin rash ^†	0/31 (0.00%)	0	2/30 (6.67%)	2
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Dr. Peter Kosa (Staff Scientist)
Organization:	National Institutes of Allergy and Infectious Diseases
Phone:	(301) 731-6444
EMail:	peter.kosa@nih.gov

Publications:

Albrecht P, Ringelstein M, Muller AK, Keser N, Dietlein T, Lappas A, Foerster A, Hartung HP, Aktas O, Methner A. Degeneration of retinal layers in multiple sclerosis subtypes quantified by optical coherence tomography. Mult Scler. 2012 Oct;18(10):1422-9. doi: 10.1177/1352458512439237. Epub 2012 Mar 2.

Andrews HE, Nichols PP, Bates D, Turnbull DM. Mitochondrial dysfunction plays a key role in progressive axonal loss in Multiple Sclerosis. Med Hypotheses. 2005;64(4):669-77. doi: 10.1016/j.mehy.2004.09.001.

Artuch R, Aracil A, Mas A, Colome C, Rissech M, Monros E, Pineda M. Friedreich's ataxia: idebenone treatment in early stage patients. Neuropediatrics. 2002 Aug;33(4):190-3. doi: 10.1055/s-2002-34494.

Layout table for additonal information

Responsible Party:	National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
ClinicalTrials.gov Identifier:	NCT01854359
Other Study ID Numbers:	130088 13-I-0088
First Submitted:	May 11, 2013
First Posted:	May 15, 2013
Results First Submitted:	October 30, 2019
Results First Posted:	May 19, 2021
Last Update Posted:	May 19, 2021

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