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Multiple SclerosisPhase 1/2NCT01854359

Idebenone for Primary Progressive Multiple Sclerosis

A Phase 1/2 study testing Idebenone in people with Multiple Sclerosis and Primary Progressive Multiple Sclerosis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Idebenone
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
61 participants
Where
1 siteUnited States
Study dates
12 Mar 2013to 31 Oct 2018
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Completion of 3 years in study IPPoMS (Protocol Number 09-N-0197)
  • Able to provide informed consent
  • Adults, at least 18 years of age
  • Willing to participate in all aspects of trial design and follow-up
  • If able to become pregnant or to father a child, agreeing to commit to the use of a reliable/accepted method of birth control (i.e. hormonal contraception (birth control pills, injected hormones, vaginal ring), intrauterine device, barrier methods with spermicide (diaphragm with spermicide, condom with spermicide) or surgical sterilization (hysterectomy, tubal ligation, or vasectomy)) for the duration of treatment arm of the study

Who cannot join

  • Pregnant or lactating women. All women of child-bearing potential must have a negative pregnancy test
  • Patients dropping out of IPPoMS due to adverse events (AE) considered related to study medication

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: Open Label Extension Trial of Idebenone for Primary Progressive Multiple Sclerosis

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.
Read more

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.
Read the detailed description

OBJECTIVE:

A Phase I/II clinical trial is being conducted to investigate the safety, therapeutic efficacy and mechanism of action of idebenone in primary-progressive multiple sclerosis (PP-MS) patients (IPPoMS (Protocol Number 09-N-0197). Patients who have completed the 2-year treatment period of IPPoMS, may enter into this open-label extension study (IPPoMS-E) if they are found to be eligible by the Investigator and desire treatment with idebenone despite remaining blinded as to their allocation to active treatment versus placebo during the IPPoMS trial. The aim of this open-label extension study is gather additional data on safety, efficacy and effects of idebenone on cerebrospinal fluid (CSF) biomarkers in these patients over a period of 1 year. This study will provide open-label idebenone for patients with PP-MS, previously randomized to idebenone or to placebo in the blinded phase of IPPoMS.

STUDY POPULATION:

Patients who were previously enrolled in the IPPoMS (Protocol Number 09-N-0197) will be invited to participate in the trial. The same idebenone dose used in the randomized clinical trial (2250 mg/day) will be used in this study.

DESIGN:

This is a single group, open-label safety and efficacy extension trial with a one year treatment period. Patient-specific biomarkers of disease progression, CSF biomarkers of oxidative stress, longitudinal neuroimaging including quantitative measures of CNS tissue destruction and clinical data will be collected as in the randomized study.

OUTCOME MEASURES:

The measurement and collection of data will be performed as in the randomized trial. Quantitative neuroimaging measures of central nervous system (CNS: i.e. brain and spinal cord) tissue destruction and clinical and functional measures of neurological disability will be collected every 6-12 months. Additionally, biomarkers focusing on analysis of reactive oxygen species (ROS) and oxidative stress will be collected every 12 months. The primary outcome measure defined in the IPPoMS trial will be also utilized in IPPoMS-E. For patients originally randomized to placebo, patient-specific slopes of disease progression during 2 years of placebo therapy (as measured by primary and secondary outcomes) will be compared to patient-specific slopes of disease progression during 1 year of open label idebenone therapy. Combination of IPPoMS and IPPoMS-E trials will significantly expand paired no therapy vs. idebenone therapy CSF samples for biomarker studies. It will also provide (for the subgroup of subjects who were originally randomized to idebenone) longitudinal CSF samples on idebenone therapy (collected 2 years apart). This will allow calculations of intra-individual changes in CSF biomarkers on and off idebenone therapy, which may provide important insight into the mechanism of action of idebenone in PP-MS.

Being tested
Idebenone
Keywords
Multiple Sclerosis, Extension Trial
Medical subject headings
Multiple Sclerosis, Multiple Sclerosis, Chronic Progressive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IdebenoneDrug

Study groups in NCT01854359
Study groupRoleWhat they receive
Active treatmentOtherIdebenone (150mg tablets) administered orally as five tablets, three times per day with food.
Receives: Drug: Idebenone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Area Under the Curve (AUC) of the Combinatorial Weight-Adjusted Disability Score (CombiWISE)

    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, 18, and 24)
    3. 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.

    Measured: 1-year pre-treatment baseline vs 2-year randomized double-blind phased vs 1-year treatment period

Secondary outcomes (4)

  1. Slopes of 25 Foot Walk (25FW) Time

    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"

    Measured: 3-years double-blind phase and 1-year extension phase

  2. Slopes of 9 Hole Peg Test (9HPT) Time

    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.

    Measured: 3-years double-blind phase and 1-year extension phase

  3. Slopes of Expanded Disability Status Scale (EDSS) Score

    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.

    Measured: 3-years double-blind phase and 1-year extension phase

  4. Change in Slopes of Scripps Neurological Rating Scale (SNRS) Score

    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.

    Measured: 3-years double-blind phase and 1-year extension phase

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 May 2013 (estimated)
  2. Study start12 Mar 2013
  3. Primary completion31 Oct 2018
  4. Study completion31 Oct 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
61 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01854359
Sponsor's protocol ID
130088
Other IDs
13-I-0088
Status last verified
Oct 2018
First submitted
11 May 2013
Last updated
19 May 2021
FDA-regulated drug
Yes

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.

    PubMed 22389411

  • 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.

    PubMed 15694681

  • 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.

    PubMed 12368988

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Idebenone in people with Multiple Sclerosis and Primary Progressive Multiple Sclerosis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 May 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Area Under the Curve (AUC) of the Combinatorial Weight-Adjusted Disability Score (CombiWISE) (time frame: 1-year pre-treatment baseline vs 2-year randomized double-blind phased vs 1-year treatment period). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01854359, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 May 2021.

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