Clinical Trial of Idebenone in Primary Progressive Multiple Sclerosis (IPPoMS)

NCT00950248 | Completed Phase 1 Results FDA Drug

• 3 other identifiers: 09019709-I-0197NCT00950248
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Primary Progressive Multiple Sclerosis

Keywords

Idebenone; Magnetic Resonance Imaging (MRI); Magnetic Resonance Spectroscopy; Mitochondrial Enhancer; Multiple Sclerosis; MS; Primary Progressive Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  1-year pre-treatment baseline vs 2-year treatment period

• Disability Progression Measured by EDSS-plus

  2-year treatment period

• Change in Slopes of 25FW Time From Baseline to Treatment Phase

  1-year pre-treatment baseline vs 2-year treatment period

• Change in Slopes of 9HPT Time From Baseline to Treatment Phase

  1-year pre-treatment baseline vs 2-year treatment period

• Change in Slopes of SNRS From Baseline to Treatment Phase on

  1-year pre-treatment baseline vs 2-year treatment period

Study Arms (2)

Idebenone

ACTIVE COMPARATOR

Idebenone (150mg tablets) administered orally as five tablets, three times per day with food.

Drug: Idebenone

Placebo

PLACEBO COMPARATOR

Placebo tablets administered orally as five tablets, three times per day with food.

Other: placebo

Interventions

Idebenone DRUG

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)

Also known as: SNT-MC17/F02

Idebenone

placebo OTHER

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)

Also known as: SNT-MC17/F03

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:
• i. Serum alanine transaminase or aspartate transaminase levels greater than 3 times the upper limit of normal values
• ii. Total white blood cell count \< 3,000/mm(3)
• iii. Platelet count \< 85,000/mm(3)
• iv. Serum creatinine level \> 2.0 mg/dl or eGFR (estimated glomerular filtration rate) \<30
• v. 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (5)

• 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.

  PMID: 12368988 BACKGROUND

• Bielekova 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.

  PMID: 16585503 BACKGROUND

• Bieniek 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.

  PMID: 16793860 BACKGROUND

• Kosa 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.

  PMID: 27574516 DERIVED

• Hartung 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.

  PMID: 19847907 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis

Interventions

idebenone

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

The small sample size is a limitation of this study evaluating therapeutic intervention in a complex progressive neurological disease.

Results Point of Contact

• Title: Dr. Bibiana Bielekova
• Organization: National Institute of Allergy and Infectious Diseases, National Institutes of Health

bibi.bielekova@nih.gov

(240) 669-2724

Study Officials

• Bibiana Bielekova, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2009
• First Posted: July 31, 2009
• Study Start: November 1, 2009
• Primary Completion: April 30, 2018
• Study Completion: August 6, 2018
• Last Updated: March 19, 2019
• Results First Posted: March 7, 2019

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: available at the time of publication

Locations

US (1)