NCT01854359

Idebenone for Primary Progressive Multiple Sclerosis

Completed Phase 1, PHASE2 Results posted Last updated 19 May 2021

What this trial tests

Phase 1, PHASE2 trial testing Idebenone in Multiple Sclerosis in 61 participants. Completed in 31 October 2018.

Timeline

12 March 2013

Primary endpoint
31 October 2018

31 October 2018

Quick facts

Lead sponsor	National Institute of Allergy and Infectious Diseases (NIAID)
Phase	Phase 1, PHASE2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	61
Start date	12 March 2013
Primary completion	31 October 2018
Estimated completion	31 October 2018
Sites	1 location across United States

Drugs / interventions tested

• Idebenone (IDEBENONE) — full drug profile →

Conditions studied

• Multiple Sclerosis — all drugs for Multiple Sclerosis →
• Primary Progressive Multiple Sclerosis — all drugs for Primary Progressive Multiple Sclerosis →

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Who can join

18 and older, any sex, with Multiple Sclerosis or Primary Progressive Multiple Sclerosis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Area Under the Curve (AUC) of the Combinatorial Weight-Adjusted Disability Score (CombiWISE) Primary · 1-year pre-treatment baseline vs 2-year randomized double-blind phased vs 1-year treatment period

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: 1. pre-treatment baseline during the 09-I-0197 trial (from Months -12, -6, and 0) 2. double-blind phase during the 09-I-0197 trial (from Months 0, 6, 12,

Group	Value	95% CI
Pre-treatment Baseline (Placebo Group)	1.55	± 2.02
Double-blind Phase (Placebo Group)	0.80	± 1.96
Extension Phase (Placebo Group)	0.46	± 1.93
Pre-treatment Baseline (Active Treatment Group)	0.89	± 1.81
Double-blind Phase (Active Treatment Group)	0.75	± 1.82
Extension Phase (Active Treatment Group)	1.30	± 2.30

Slopes of 25 Foot Walk (25FW) Time Secondary · 3-years double-blind phase and 1-year extension phase

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"

Group	Value	95% CI
Placebo Arm of the 09-I-0197	0.04322	± 0.009617
Extension Phase (Placebo Arm)	-0.00531	± 0.01599
Active Treatment Arm of the 09-I-0197	0.04031	± 0.0106
Extension Phase (Active Treatment Arm)	0.03401	± 0.01286

Slopes of 9 Hole Peg Test (9HPT) Time Secondary · 3-years double-blind phase and 1-year extension phase

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"

Group	Value	95% CI
Placebo Arm of the 09-I-0197	0.000665	± 0.000491
Extension Phase (Placebo Arm)	0.000947	± 0.001189
Active Treatment Arm of the 09-I-0197	0.000718	± 0.000462
Extension Phase (Active Treatment Arm)	0.001086	± 0.000614

Slopes of Expanded Disability Status Scale (EDSS) Score Secondary · 3-years double-blind phase and 1-year extension phase

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.

Group	Value	95% CI
Placebo Arm of the 09-I-0197	0.1447	± 0.05778
Extension Phase (Placebo Arm)	0.1435	± 0.07625
Active Treatment Arm of the 09-I-0197	0.1107	± 0.03651
Extension Phase (Active Treatment Arm)	0.1584	± 0.09479

Change in Slopes of Scripps Neurological Rating Scale (SNRS) Score Secondary · 3-years double-blind phase and 1-year extension phase

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.

Group	Value	95% CI
Placebo Arm of the 09-I-0197	-1.8838	± 0.4829
Extension Phase (Placebo Arm)	-2.1655	± 1.0735
Active Treatment Arm of the 09-I-0197	-2.009	± 0.3789
Extension Phase (Active Treatment Arm)	-2.7263	± 1.0073

Adverse events — posted to ClinicalTrials.gov

Time frame: 1 year. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Active Treatment in 09-I-0197

Serious: 4/31 (13%)

Deaths: 0/31

Placebo in 09-I-0197

Serious: 4/30 (13%)

Deaths: 0/30

Serious adverse events (10 terms)

Reaction	System	Active Treatment in 09-I-0…	Placebo in 09-I-0197
Elevated liver enzynes	Blood and lymphatic system disorders	—	—
Myocardial infarction	Cardiac disorders	—	—
decreased ejection fraction	Cardiac disorders	—	—
stomach cancer	Gastrointestinal disorders	—	—
severe constipation	Gastrointestinal disorders	—	—
gallstones	Hepatobiliary disorders	—	—
ruptured apendix	Infections and infestations	—	—
broken ribs	Injury, poisoning and procedural complications	—	—
broken femur	Injury, poisoning and procedural complications	—	—
chest tightness	Cardiac disorders	—	—

Other adverse events (22 terms — click to expand)

Reaction	System	Active Treatment in 09-I-0…	Placebo in 09-I-0197
fall	Injury, poisoning and procedural complications	—	—
fractured bone	Injury, poisoning and procedural complications	—	—
urinary tract infection	Infections and infestations	—	—
back pain	Musculoskeletal and connective tissue disorders	—	—
diarrhea	Gastrointestinal disorders	—	—
injured meniscus	Injury, poisoning and procedural complications	—	—
skin rash	Skin and subcutaneous tissue disorders	—	—
basal cell carcinoma	Skin and subcutaneous tissue disorders	—	—
benign thyroid nodule	Endocrine disorders	—	—
cellulitis	Skin and subcutaneous tissue disorders	—	—
chest pain	Cardiac disorders	—	—
dehydration	Metabolism and nutrition disorders	—	—
edema	Musculoskeletal and connective tissue disorders	—	—
H1N1 influenza	Infections and infestations	—	—
hair loss	Skin and subcutaneous tissue disorders	—	—
hypertension	Cardiac disorders	—	—
increased mobility problems	General disorders	—	—
nausea	Gastrointestinal disorders	—	—
penumonia	Infections and infestations	—	—
radiculopathy	Musculoskeletal and connective tissue disorders	—	—
retinal detachment	Eye disorders	—	—
transient graying of vision	Eye disorders	—	—

Most-reported serious reactions: Elevated liver enzynes, Myocardial infarction, decreased ejection fraction, stomach cancer, severe constipation, gallstones, ruptured apendix, broken ribs.

Data from ClinicalTrials.gov NCT01854359 adverse events section.

Sponsor's own description

Background:

\- The Idebenone in Patients With Primary Progressive Multiple Sclerosis (IPPoMS) trial tested a new drug for multiple sclerosis. In the IPPoMS trial, participants took either idebenone or placebo. Researchers want to give idebenone to all participants for 1 year. It is still not certain whether idebenone can slow the progression of multiple sclerosis, but this study may help answer that question.

Objectives:

* To provide idebenone to all participants on the IPPoMS trial.
* To collect data on the safety and effectiveness of idebenone for primary progressive multiple sclerosis.

Eligibility:

\- Individuals at least 18 years of age who have completed 3 years in the IPPoMS trial.

Design:

* The first study visit for this trial will happen on the same day as the last visit for the IPPoMS trial.
* Participants will provide a blood samples and will have a lumbar puncture. They will also receive a new supply of idebenone to take three times a day with food. They will keep a diary to report on any side effects.
* After this first treatment visit, participants will have two follow-up visits to the NIH 6 months apart. These visits may be scheduled over multiple days. Participants will provide blood and urine samples. They will also have imaging studies of the brain and spine.
* Participants will have phone calls with the study researchers to provide updates on their condition and any side effects.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Mitochondrial Dysfunction and Multiple Sclerosis.
   Barcelos IP, Troxell RM, Graves JS. · · 2019 · cited 159× · PMID 31083577 · DOI 10.3390/biology8020037
2. Pharmacological advances in mitochondrial therapy.
   Singh A, Faccenda D, Campanella M. · · 2021 · cited 88× · PMID 33647769 · DOI 10.1016/j.ebiom.2021.103244
3. Therapeutic Advances and Future Prospects in Progressive Forms of Multiple Sclerosis.
   Shirani A, Okuda DT, Stüve O. · · 2016 · cited 69× · PMID 26729332 · DOI 10.1007/s13311-015-0409-z
4. Precise modulation and use of reactive oxygen species for immunotherapy.
   Li X, Gao J, Wu C, Wang C, et al · · 2024 · cited 51× · PMID 38748805 · DOI 10.1126/sciadv.adl0479
5. Diagnosis and Management of Progressive Multiple Sclerosis.
   Macaron G, Ontaneda D. · · 2019 · cited 47× · PMID 31362384 · DOI 10.3390/biomedicines7030056
6. Idebenone: Novel Strategies to Improve Its Systemic and Local Efficacy.
   Montenegro L, Turnaturi R, Parenti C, Pasquinucci L. · · 2018 · cited 36× · PMID 29401722 · DOI 10.3390/nano8020087
7. Failed, Interrupted, or Inconclusive Trials on Neuroprotective and Neuroregenerative Treatment Strategies in Multiple Sclerosis: Update 2015-2020.
   Huntemann N, Rolfes L, Pawlitzki M, Ruck T, et al · · 2021 · cited 30× · PMID 34086251 · DOI 10.1007/s40265-021-01526-w
8. A Personalized Approach in Progressive Multiple Sclerosis: The Current Status of Disease Modifying Therapies (DMTs) and Future Perspectives.
   D'Amico E, Patti F, Zanghì A, Zappia M. · · 2016 · cited 25× · PMID 27763513 · DOI 10.3390/ijms17101725