Primary Progressive Multiple SclerosisPhase 1/2IPPoMSNCT00950248
Clinical Trial of Idebenone in Primary Progressive Multiple Sclerosis (IPPoMS)
A Phase 1/2 study testing Idebenone in people with Primary Progressive Multiple Sclerosis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
Background: Multiple sclerosis (MS) is an inflammatory disorder of the central nervous system that progressively weakens and destroys the pathways of the nervous system. About 10 percent to 15 percent of patients develop primary-progressive MS (PP-MS), characterized by progressive accumulation of disability from the… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Primary Progressive Multiple Sclerosis
- What is being tested?
- Idebenone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 85 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Nov 2009to 6 Aug 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- PP-MS as determined by the 2005 modification of McDonald s diagnostic criteria
- Age from 18-65 years (inclusive)
- Expanded Disability Status Scale (EDSS) measure of neurological disability from 1 (no disability, clinical signs only) to 7 (ambulatory with bilateral support)
- Able to provide informed consent
- 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 in a partner)) for the duration of treatment arm of the study
- Not receiving any immunomodulatory/immunosuppressive therapies for a period of at least 3 months before enrollment in the study
- No exposure to idebenone, coenzyme-Q(10) or other dietary supplements (such as antioxidants, mitochondrial-function promoting supplements or vitamins in excess of 3 times recommended daily doses) for a period of at least 1 month before enrollment in the study
Who cannot join
- Alternative diagnoses that can explain neurological disability and MRI findings
- Clinically significant medical disorders that, in the judgment of the investigators, could cause CNS tissue damage or limit its repair, or might expose the patient to undue risk of harm or prevent the patient from completing the study
- History of hypersensitivity reaction to idebenone or coenzyme-Q (10)
- Pregnant or lactating women. All women of child-bearing potential must have a negative pregnancy test prior to the medication phase of the study.
- Abnormal screening/baseline blood tests exceeding any of the limits defined below:
- Serum alanine transaminase or aspartate transaminase levels greater than 3 times the upper limit of normal values
Show all 11Show fewer
- Total white blood cell count < 3,000/mm(3)
- Platelet count < 85,000/mm(3)
- Serum creatinine level > 2.0 mg/dl or eGFR (estimated glomerular filtration rate) <30
- Positive pregnancy test
- Patients who are receiving any immunosuppressive therapies (including cytostatic agents) due to the concern that these drugs may contribute to neurodegeneration or limit CNS repair
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Double Blind Placebo-Controlled Phase I/II Clinical Trial of Idebenone in Patients With Primary Progressive Multiple Sclerosis
Background:
- Multiple sclerosis (MS) is an inflammatory disorder of the central nervous system that progressively weakens and destroys the pathways of the nervous system. About 10 percent to 15 percent of patients develop primary-progressive MS (PP-MS), characterized by progressive accumulation of disability from the disease onset, without any marked improvements or relapses. There are currently no effective treatments for PP-MS.
- Idebenone is a manmade drug that is similar to a naturally occurring compound known as coenzyme Q10, a common dietary supplement. Research data suggest that idebenone may be able to limit demyelination and death of brain cells and thereby slow or halt the progression of neurological dysfunction such as that occurring in MS.
Read more
Objectives:
- To evaluate the safety and effectiveness of using idebenone to treat primary progressive MS.
Eligibility:
- Individuals between 18 and 65 years of age who have been diagnosed with primary progressive multiple sclerosis.
Design:
- The study will last 3 years and will be divided into two parts: a 1-year pretreatment baseline and 2 years of treatment with either idebenone or a placebo.
- Pre-treatment study: approximately 5 clinic visits over 1 year.
- Visit 1: Comprehensive medical history and neurological examination, with brain scans and neurological tests.
- Visit 2: Magnetic resonance imaging (MRI) scan of the spine and lymphocytapheresis (withdrawal of white blood cells for testing).
- Visit 3: Lumbar puncture.
- Visit 4: Skin biopsy.
- Visit 5: Repeat MRI of the brain and spinal cord, as well as neurological tests; these tests will be scheduled over 2 days.
- After the five pretreatment visits, patients will receive a 6-month supply of study medication (either idebenone or a placebo) to take three times a day with food
- Patients will continue to have regular followup clinic visits with brain MRI scans, blood tests, and other evaluations of brain and nervous system function. Randomly selected participants will have additional MRI scans for further safety precautions.
Read the detailed description
Objective: The goal of this study is to assess the safety, therapeutic efficacy and mechanism of action of idebenone in primary-progressive multiple sclerosis (PP-MS) patients.
Study Population: Adult, untreated patients with PP-MS with disability ranging from none to moderately severe will be included in the trial. The upper age limit in this study has been set at 65; setting an age limit should permit us to focus on the potential neuroprotective effect of idebenone in PP-MS and limit the confounding factor of the natural aging process and its known negative influence on neuro-regeneration. Published data indicate that higher doses (10-50 mg/kg) of idebenone per day are required for beneficial effects on neurological disability in comparison to the lower doses (5-10mg/kg) that are sufficient for beneficial effects on cardiac/systemic functions in Friedreich s ataxia (FRDA) patients. Therefore, in order to target the CNS compartment, we will use a daily dose of 2250mg (750mg 3 times per day), which will provide target values of 10-50mg/kg for virtually all adult patients.
Design: This is a Phase I/II safety/efficacy trial with an adaptive trial design: one year of pretreatment baseline period serves the dual purpose of collecting patient-specific biomarkers of disease progression and collecting longitudinal neuroimaging and clinical data for selection of primary outcome measures. This baseline period is then followed by a double-blind, idebenone versus placebo treatment phase for a total of 2 years. Based on preliminary sample size estimates, current enrollment calls for a total of 66 patients (33 per arm).
Outcome Measures: Quantitative neuroimaging measures of central nervous system (CNS: i.e. brain and spinal cord) tissue destruction and clinical and functional (i.e. electrophysiological) 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 trial is currently powered using progression of brain atrophy as detected by SIENA methodology as the primary outcome measure. However, this may not be the most sensitive outcome available. In recognition of this, the trial has an adaptive design: i.e. it incorporates analysis of progression of CNS tissue destruction as measured by quantitative MRI markers and clinical/paraclinical markers defined as secondary outcome measures in the first 30 enrolled patients during the one year pre-treatment baseline, before randomization. All defined outcome measures collected in the first 30 enrolled patients will be transformed into z-scores and compared for the robustness of longitudinal change over the coefficient of variation. This will permit to select the most sensitive and most accurate outcome measure for detecting progression of CNS tissue damage. As a result, the primary outcome measure of this trial will be the comparison of individualized rates of brain atrophy progression between the idebenone and placebo groups after 2 years of treatment, unless the predetermined analysis of the pre-treatment baseline period in the first 30 enrolled subjects determines that one of the predefined secondary outcome measures has a higher z-score than brain atrophy measurement. In this case, the primary outcome would be the efficacy of idebenone versus placebo in inhibiting patient-specific slopes of functional or structural deterioration as measured by this more sensitive biomarker of CNS tissue destruction, yet to be defined by the analysis of the 1-year longitudinal data from pre-treatment baseline.
- Conditions
- Primary Progressive Multiple Sclerosis
- Being tested
- Idebenone, placebo
- Keywords
- Idebenone, Magnetic Resonance Imaging (MRI), Magnetic Resonance Spectroscopy, Mitochondrial Enhancer, Multiple Sclerosis, MS, Primary Progressive Multiple Sclerosis
- Medical subject headings
- Multiple Sclerosis, Chronic Progressive, Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IdebenoneDrug
Also called SNT-MC17/F02
idebenone, lactose monohydrate, microcrystalline cellulose, croscarmellose sodium povidone, magnesium stearate, silicon dioxide, film-coat: Opadry II 85F23495 (consisting of: aluminium lake, FD\&C yellow #6, macrogol/PEG 3550, polyvinylalcohol, titanium dioxide, talc)
placeboOther
Also called SNT-MC17/F03
lactose monohydrate, microcrystalline cellulose, magnesium stearate, film-coat: Opadry II 85F23495 (consisting of: aluminium lake, FD\&C yellow #6, macrogol/PEG 3550, polyvinylalcohol, titanium dioxide, talc)
| Study group | Role | What they receive |
|---|---|---|
| Idebenone | Active comparator | Idebenone (150mg tablets) administered orally as five tablets, three times per day with food. Receives: Drug: Idebenone |
| Placebo | Placebo comparator | Placebo tablets administered orally as five tablets, three times per day with food. Receives: Other: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in the Area Under the Curve (AUC) of the Combinatorial Weight-Adjusted Disability Score (CombiWISE) From Baseline to Treatment Phase
The AUCs of the CombiWISE scores during the 2-year treatment period was analyzed using an Analysis of Covariance (ANCOVA) model with the AUC of the pre-treatment CombiWISE scores, Baseline (Month 0) CombiWISE score and Baseline age as covariates.
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 the pre-treatment baseline phase (from Months -12, -6, and 0) and for the double-blind phase (from Months 0, 6, 12, 18, and 24).
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 treatment period
Secondary outcomes (6)
Change in the AUC of Individualized Rates of Enlargement of Ventricular Volume From Baseline to Treatment Phase
The AUCs of the Ventricular volume scores (individualized rates of enlargement of segmented volume of lateral and 3rd ventricles) during the baseline and the 2-year treatment period were assessed using an ANCOVA model with the AUC of the pre-treatment Volumetric score, Baseline (Month 0) Volumetric score, and group as covariates.
The AUC values were calculated for both the pre-treatment baseline phase (from Months -12, -6, and 0) and for the double-blind phase (from Months 0, 6, 12, 18 and 24).
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 treatment period
Disability Progression Measured by EDSS-plus
Categorical time-to-event endpoints (EDSS-plus) were analyzed using Cox Proportional hazards models, with treatment group as a covariate. The EDSS-plus event was defined as disability progression on at least 1 of 3 components [EDSS, 25FW, and/or non-dominant hand 9HPT]) confirmed 6 months apart and with a ≥ 20% minimum threshold change for 25FW and non-dominant hand 9HPT).
The patients who did not have an event during the study were censored at the time of the last assessment of EDSS-plus. The number of months from the date of first dose to date of event or censoring were used as endpoint. The measure is time to disease progression and unit of this measure is months.
Measured: 2-year treatment period
Change in Slopes of 25FW Time From Baseline to Treatment Phase
Lower extremity disability was measured by an average of two trials of timed 25 foot walk assessed at month -12, -6, and 0 for the baseline phase and at month 0, 6, 12, 18, and 24 for the treatment phase. The progression rate was calculated as a difference between baseline and treatment slopes using a piecewise linear mixed-effect model with breaking point at month 0.
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: 1-year pre-treatment baseline vs 2-year treatment period
Change in Slopes of 9HPT Time From Baseline to Treatment Phase
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 at month -12, -6, and 0 for the baseline phase and at month 0, 6, 12, 18, and 24 for the treatment phase. The progression rate was calculated as a difference between baseline and treatment slopes using a piecewise linear mixed-effect model with breaking point at month 0.
Measured: 1-year pre-treatment baseline vs 2-year treatment period
Change in Slopes of SNRS From Baseline to Treatment Phase on
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 at month -12, -6, and 0 for the baseline phase and at month 0, 6, 12, 18, and 24 for the treatment phase. The progression rate was calculated as a difference between baseline and treatment slopes using a piecewise linear mixed-effect model with breaking point at month 0.
Measured: 1-year pre-treatment baseline vs 2-year treatment period
Change in Slopes of EDSS From Baseline to Treatment Phase
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 MS. EDSS was assessed at month -12, -6, and 0 for the baseline phase and at month 0, 6, 12, 18, and 24 for the treatment phase.The progression rate was calculated as a difference between baseline and treatment slopes using a piecewise linear mixed-effect model with breaking point at month 0.
Measured: 1-year pre-treatment baseline vs 2-year treatment period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2009 (estimated)
- Study start1 Nov 2009
- Primary completion30 Apr 2018
- Study completion6 Aug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Primary Progressive Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 85 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Bibiana Bielekova, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00950248
- Sponsor's protocol ID
- 090197
- Other IDs
- 09-I-0197, NCT00950248
- Acronym
- IPPoMS
- Status last verified
- Aug 2018
- First submitted
- 30 Jul 2009
- Last updated
- 19 Mar 2019
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- Individual data sharing
- Yes: raw data will be shared as supplementary material in publication
Publications
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 12368988Bielekova B, Catalfamo M, Reichert-Scrivner S, Packer A, Cerna M, Waldmann TA, McFarland H, Henkart PA, Martin R. Regulatory CD56(bright) natural killer cells mediate immunomodulatory effects of IL-2Ralpha-targeted therapy (daclizumab) in multiple sclerosis. Proc Natl Acad Sci U S A. 2006 Apr 11;103(15):5941-6. doi: 10.1073/pnas.0601335103. Epub 2006 Apr 3.
PubMed 16585503Bieniek M, Altmann DR, Davies GR, Ingle GT, Rashid W, Sastre-Garriga J, Thompson AJ, Miller DH. Cord atrophy separates early primary progressive and relapsing remitting multiple sclerosis. J Neurol Neurosurg Psychiatry. 2006 Sep;77(9):1036-9. doi: 10.1136/jnnp.2006.094748. Epub 2006 Jun 22.
PubMed 16793860Kosa P, Ghazali D, Tanigawa M, Barbour C, Cortese I, Kelley W, Snyder B, Ohayon J, Fenton K, Lehky T, Wu T, Greenwood M, Nair G, Bielekova B. Development of a Sensitive Outcome for Economical Drug Screening for Progressive Multiple Sclerosis Treatment. Front Neurol. 2016 Aug 15;7:131. doi: 10.3389/fneur.2016.00131. eCollection 2016.
PubMed 27574516Hartung HP, Aktas O. Bleak prospects for primary progressive multiple sclerosis therapy: downs and downs, but a glimmer of hope. Ann Neurol. 2009 Oct;66(4):429-32. doi: 10.1002/ana.21880. No abstract available.
PubMed 19847907
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Double Blind Placebo-Controlled Phase I/II Clinical Trial of Idebenone in Patients With Primary Progressive Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT00950248
- Acronym / sponsor ID
- IPPoMS / 090197
- Conditions
- Primary Progressive Multiple Sclerosis
- Keywords
- Idebenone, Magnetic Resonance Imaging (MRI), Magnetic Resonance Spectroscopy, Mitochondrial Enhancer, Multiple Sclerosis, MS, Primary Progressive Multiple Sclerosis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 85 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 1 Nov 2009 (actual)
- Primary completion
- 30 Apr 2018 (actual)
- Study completion
- 6 Aug 2018 (actual)
- First posted
- 31 Jul 2009 (estimated)
- Results
- Posted 7 Mar 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- Multiple sclerosis (MS) is an inflammatory disorder of the central nervous system that progressively weakens and destroys the pathways of the nervous system. About 10 percent to 15 percent of patients develop primary-progressive MS (PP-MS), characterized by progressive accumulation of disability from the disease onset, without any marked improvements or relapses. There are currently no effective treatments for PP-MS.
- Idebenone is a manmade drug that is similar to a naturally occurring compound known as coenzyme Q10, a common dietary supplement. Research data suggest that idebenone may be able to limit demyelination and death of brain cells and thereby slow or halt the progression of neurological dysfunction such as that occurring in MS.
Objectives:
- To evaluate the safety and effectiveness of using idebenone to treat primary progressive MS.
Eligibility:
- Individuals between 18 and 65 years of age who have been diagnosed with primary progressive multiple sclerosis.
Design:
- The study will last 3 years and will be divided into two parts: a 1-year pretreatment baseline and 2 years of treatment with either idebenone or a placebo.
- Pre-treatment study: approximately 5 clinic visits over 1 year.
- Visit 1: Comprehensive medical history and neurological examination, with brain scans and neurological tests.
- Visit 2: Magnetic resonance imaging (MRI) scan of the spine and lymphocytapheresis (withdrawal of white blood cells for testing).
- Visit 3: Lumbar puncture.
- Visit 4: Skin biopsy.
- Visit 5: Repeat MRI of the brain and spinal cord, as well as neurological tests; these tests will be scheduled over 2 days.
- After the five pretreatment visits, patients will receive a 6-month supply of study medication (either idebenone or a placebo) to take three times a day with food
- Patients will continue to have regular followup clinic visits with brain MRI scans, blood tests, and other evaluations of brain and nervous system function. Randomly selected participants will have additional MRI scans for further safety precautions.
Detailed description
Objective: The goal of this study is to assess the safety, therapeutic efficacy and mechanism of action of idebenone in primary-progressive multiple sclerosis (PP-MS) patients.
Study Population: Adult, untreated patients with PP-MS with disability ranging from none to moderately severe will be included in the trial. The upper age limit in this study has been set at 65; setting an age limit should permit us to focus on the potential neuroprotective effect of idebenone in PP-MS and limit the confounding factor of the natural aging process and its known negative influence on neuro-regeneration. Published data indicate that higher doses (10-50 mg/kg) of idebenone per day are required for beneficial effects on neurological disability in comparison to the lower doses (5-10mg/kg) that are sufficient for beneficial effects on cardiac/systemic functions in Friedreich s ataxia (FRDA) patients. Therefore, in order to target the CNS compartment, we will use a daily dose of 2250mg (750mg 3 times per day), which will provide target values of 10-50mg/kg for virtually all adult patients.
Design: This is a Phase I/II safety/efficacy trial with an adaptive trial design: one year of pretreatment baseline period serves the dual purpose of collecting patient-specific biomarkers of disease progression and collecting longitudinal neuroimaging and clinical data for selection of primary outcome measures. This baseline period is then followed by a double-blind, idebenone versus placebo treatment phase for a total of 2 years. Based on preliminary sample size estimates, current enrollment calls for a total of 66 patients (33 per arm).
Outcome Measures: Quantitative neuroimaging measures of central nervous system (CNS: i.e. brain and spinal cord) tissue destruction and clinical and functional (i.e. electrophysiological) 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 trial is currently powered using progression of brain atrophy as detected by SIENA methodology as the primary outcome measure. However, this may not be the most sensitive outcome available. In recognition of this, the trial has an adaptive design: i.e. it incorporates analysis of progression of CNS tissue destruction as measured by quantitative MRI markers and clinical/paraclinical markers defined as secondary outcome measures in the first 30 enrolled patients during the one year pre-treatment baseline, before randomization. All defined outcome measures collected in the first 30 enrolled patients will be transformed into z-scores and compared for the robustness of longitudinal change over the coefficient of variation. This will permit to select the most sensitive and most accurate outcome measure for detecting progression of CNS tissue damage. As a result, the primary outcome measure of this trial will be the comparison of individualized rates of brain atrophy progression between the idebenone and placebo groups after 2 years of treatment, unless the predetermined analysis of the pre-treatment baseline period in the first 30 enrolled subjects determines that one of the predefined secondary outcome measures has a higher z-score than brain atrophy measurement. In this case, the primary outcome would be the efficacy of idebenone versus placebo in inhibiting patient-specific slopes of functional or structural deterioration as measured by this more sensitive biomarker of CNS tissue destruction, yet to be defined by the analysis of the 1-year longitudinal data from pre-treatment baseline.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Idebenone | Active comparator | Drug: IdebenoneIdebenone (150mg tablets) administered orally as five tablets, three times per day with food. |
| Placebo | Placebo comparator | Other: placeboPlacebo tablets administered orally as five tablets, three times per day with food. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
Key exclusion criteria (11 listed)
- Alternative diagnoses that can explain neurological disability and MRI findings
- Clinically significant medical disorders that, in the judgment of the investigators, could cause CNS tissue damage or limit its repair, or might expose the patient to undue risk of harm or prevent the patient from completing the study
- History of hypersensitivity reaction to idebenone or coenzyme-Q (10)
- Pregnant or lactating women. All women of child-bearing potential must have a negative pregnancy test prior to the medication phase of the study.
- Abnormal screening/baseline blood tests exceeding any of the limits defined below:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IdebenoneAlso: SNT-MC17/F02idebenone, lactose monohydrate, microcrystalline cellulose, croscarmellose sodium povidone, magnesium stearate, silicon dioxide, film-coat: Opadry II 85F23495 (consisting of: aluminium lake, FD\&C yellow #6, macrogol/PEG 3550, polyvinylalcohol, titanium dioxide, talc) | Drug | Idebenone |
| placeboAlso: SNT-MC17/F03lactose monohydrate, microcrystalline cellulose, magnesium stearate, film-coat: Opadry II 85F23495 (consisting of: aluminium lake, FD\&C yellow #6, macrogol/PEG 3550, polyvinylalcohol, titanium dioxide, talc) | Other | Placebo |
Primary outcome
Change in the Area Under the Curve (AUC) of the Combinatorial Weight-Adjusted Disability Score (CombiWISE) From Baseline to Treatment Phase
Time frame: 1-year pre-treatment baseline vs 2-year treatment period
The AUCs of the CombiWISE scores during the 2-year treatment period was analyzed using an Analysis of Covariance (ANCOVA) model with the AUC of the pre-treatment CombiWISE scores, Baseline (Month 0) CombiWISE score and Baseline age as covariates. 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 the pre-treatment baseline phase (from Months -12, -6, and 0) and for the double-blind phase (from Months 0, 6, 12, 18, and 24). 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.
6 secondary outcomes
Change in the AUC of Individualized Rates of Enlargement of Ventricular Volume From Baseline to Treatment Phase
Time frame: 1-year pre-treatment baseline vs 2-year treatment period
Disability Progression Measured by EDSS-plus
Time frame: 2-year treatment period
Change in Slopes of 25FW Time From Baseline to Treatment Phase
Time frame: 1-year pre-treatment baseline vs 2-year treatment period
Change in Slopes of 9HPT Time From Baseline to Treatment Phase
Time frame: 1-year pre-treatment baseline vs 2-year treatment period
Change in Slopes of SNRS From Baseline to Treatment Phase on
Time frame: 1-year pre-treatment baseline vs 2-year treatment period
Change in Slopes of EDSS From Baseline to Treatment Phase
Time frame: 1-year pre-treatment baseline vs 2-year treatment period
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 12368988Artuch 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.
- Background: PubMed 16585503Bielekova B, Catalfamo M, Reichert-Scrivner S, Packer A, Cerna M, Waldmann TA, McFarland H, Henkart PA, Martin R. Regulatory CD56(bright) natural killer cells mediate immunomodulatory effects of IL-2Ralpha-targeted therapy (daclizumab) in multiple sclerosis. Proc Natl Acad Sci U S A. 2006 Apr 11;103(15):5941-6. doi: 10.1073/pnas.0601335103. Epub 2006 Apr 3.
- Background: PubMed 16793860Bieniek M, Altmann DR, Davies GR, Ingle GT, Rashid W, Sastre-Garriga J, Thompson AJ, Miller DH. Cord atrophy separates early primary progressive and relapsing remitting multiple sclerosis. J Neurol Neurosurg Psychiatry. 2006 Sep;77(9):1036-9. doi: 10.1136/jnnp.2006.094748. Epub 2006 Jun 22.
- Derived from this study: PubMed 27574516Kosa P, Ghazali D, Tanigawa M, Barbour C, Cortese I, Kelley W, Snyder B, Ohayon J, Fenton K, Lehky T, Wu T, Greenwood M, Nair G, Bielekova B. Development of a Sensitive Outcome for Economical Drug Screening for Progressive Multiple Sclerosis Treatment. Front Neurol. 2016 Aug 15;7:131. doi: 10.3389/fneur.2016.00131. eCollection 2016.
- Derived from this study: PubMed 19847907Hartung HP, Aktas O. Bleak prospects for primary progressive multiple sclerosis therapy: downs and downs, but a glimmer of hope. Ann Neurol. 2009 Oct;66(4):429-32. doi: 10.1002/ana.21880. No abstract available.
- Individual participant dataSharing planned: Yes. raw data will be shared as supplementary material in publication
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REAL-MS: Observational Database Study of AHSCT and MS Therapies
Multiple Sclerosis, Multiple Sclerosis (MS) - Relapsing-remitting
RecruitingPhase 1
A Study to Assess the Safety and Clinical Activity of Azer-cel in Participants With B-cell Mediated Autoimmune Disorders
B-cell Mediated Autoimmune Disorders
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bibiana Bielekova, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Idebenone in people with 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 8 inclusion and 11 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 Mar 2019. 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. Some participants in this study may receive a placebo. 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 7 Mar 2019). 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?
Change in the Area Under the Curve (AUC) of the Combinatorial Weight-Adjusted Disability Score (CombiWISE) From Baseline to Treatment Phase (time frame: 1-year pre-treatment baseline vs 2-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 NCT00950248, which also lists 5 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 Mar 2019.