Study to Assess Whether GSK239512 Can Remyelinate Lesions in Subjects With Relapsing Remitting Multiple Sclerosis
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT01772199 |
Recruitment Status :
Completed
First Posted : January 21, 2013
Last Update Posted : August 16, 2016
|
- Study Details
- Tabular View
- Results Submitted
- Disclaimer
- How to Read a Study Record
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Multiple Sclerosis, Relapsing-Remitting | Drug: GSK239512 Drug: Placebo | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 131 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Primary Purpose: | Treatment |
Official Title: | Proof of Mechanism Study to Assess the Potential of GSK239512 to Remyelinate Lesions in Subjects With Relapsing Remitting Multiple Sclerosis |
Study Start Date : | February 2013 |
Actual Primary Completion Date : | September 2014 |
Actual Study Completion Date : | September 2014 |

Arm | Intervention/treatment |
---|---|
Experimental: GSK239512 Arm
GSK239512 once daily orally, started at 10 mcg and titrated to the maximum tolerated dose, Up to the highest dose of 80 mcg (10 mcg first week, 20 mcg second week, 40 mcg third week, 80 mcg fourth week) followed by 44 week maintenance treatment period
|
Drug: GSK239512
White to almost white, round tablets. Once daily orally, started at 10 mcg and titrated to the maximum tolerated dose, Up to the highest dose of 80 mcg (10 mcg first week, 20 mcg second week, 40 mcg third week, 80 mcg fourth week) followed by 44 week maintenance treatment period |
Placebo Comparator: Placebo Arm
Placebo once daily orally
|
Drug: Placebo
White to almost white, round tablets. Once daily orally. |
- Mean change in gadolinium (Gd) enhanced (GdE) lesion magnetization transfer ratio (MTR) differences (calibrated to reference scan) from before enhancement to stable recovery (>=3 months post new GdE lesion) [ Time Frame: Up to Week 48 ]A single Baseline magnetic resonance image (MRI) prior to randomization. Following randomization, a total of 8 MRIs at approximate 6 week intervals: Week 6, Week 12, Week 18, Week 24, Week 30, Week 36, Week 42, Week 48. Reference MRI: In order to accommodate variations in MTR images acquired using different scanners, the images must be normalized to eliminate intensity shifts and contrast variations. For each scanner, images from a normal subject will be obtained and processed to serve as a calibration for each scanner prior to initiating scanning for subjects participating in the study
- Mean change in Delta MTR lesion MTR differences (calibrated to reference scan) from before lesion appearance to stable recovery (>=3 months post lesion appearance) [ Time Frame: Up to Week 48 ]A single Baseline MRI prior to randomization Following randomization, a total of 8 MRIs at approximate 6 week intervals: Week 6, Week 12, Week 18, Week 24, Week 30, Week 36, Week 42, Week 48. Reference MRI: In order to accommodate variations in MTR images acquired using different scanners, the images must be normalized to eliminate intensity shifts and contrast variations. For each scanner, images from a normal subject will be obtained and processed to serve as a calibration for each scanner prior to initiating scanning for subjects participating in the study
- Change from baseline in T2 lesion MTR at Week 48 [ Time Frame: Baseline and Week 48 ]
- Cumulative new and enlarging Gd enhancing, T2 and Combined Unique Active lesions comparing placebo to GSK239512 treated subjects [ Time Frame: Up to Week 48 ]
- Change from baseline at Week 48 in total brain volume, white matter volume and grey matter volume comparing placebo to GSK239512 treated subjects [ Time Frame: Baseline and Week 48 ]
- Cumulative number of persistent black holes and new unenhancing T1 lesion counts comparing placebo to GSK239512 treated subjects over treatment duration up to Week 48 [ Time Frame: Up to Week 48 ]
- Proportion of new GdE lesions evolving into chronic (unenhancing) T1 lesions (black holes) comparing placebo to GSK239512 treated subjects over treatment duration up to Week 48 [ Time Frame: Up to Week 48 ]
- Mean change from baseline in overall cognitive impairment and cognitive domains comparing placebo to GSK239512 treated subjects [ Time Frame: Baseline and Week 48 ]A cognitive battery (computerized battery) is included in this study to assess the impact, if any, on several cognitive functional domains. The battery will be executed twice during the screen visit to familiarize the subject with the use of the tool
- Comparison of Relapse Rates between placebo and GSK239512 treated subjects [ Time Frame: Up to 50 Weeks ]A relapse in this protocol is defined as: "patient-reported symptoms or objectively observed signs typical of an acute inflammatory demyelinating event in the central nervous system (CNS), current or historical". It must occur in the absence of fever or infection and should - follow improvement from a previous relapse, occur at least 30 days following the onset of a previous relapse, and be persistent for at least 24 hours
- Comparison of Time to First Relapse between placebo and GSK239512 [ Time Frame: Up to 50 Weeks ]A relapse in this protocol is defined as: "patient-reported symptoms or objectively observed signs typical of an acute inflammatory demyelinating event in the central nervous system (CNS), current or historical". It must occur in the absence of fever or infection and should - follow improvement from a previous relapse, occur at least 30 days following the onset of a previous relapse, and be persistent for at least 24 hours
- Comparison of the proportion of subjects Relapse Free between placebo and GSK239512 treated subjects [ Time Frame: Up to 50 Weeks ]A relapse in this protocol is defined as: "patient-reported symptoms or objectively observed signs typical of an acute inflammatory demyelinating event in the central nervous system (CNS), current or historical". It must occur in the absence of fever or infection and should - follow improvement from a previous relapse, occur at least 30 days following the onset of a previous relapse, and be persistent for at least 24 hours
- Proportion of subjects with sustained worsening of Expanded Disability Severity Scale (EDSS) over 3 months comparing placebo to GSK239512 treated subjects [ Time Frame: Up to 48 Weeks ]The EDSS is an assessment of disability specifically associated with Multiple Sclerosis. The assessment will be captured in the medical records including the detailed assessment and scoring for each functional system and domain
- Mean change from baseline in the EDSS functional systems and a subset of component assessments comparing placebo to GSK239512 treated subjects [ Time Frame: Up to 48 Weeks ]The EDSS is an assessment of disability specifically associated with Multiple Sclerosis. The assessment will be captured in the medical records including the detailed assessment and scoring for each functional system and domain
- Safety and tolerability as assessed by frequency and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to Week 50 ]
- Safety and tolerability as assessed by percentage of subjects withdrawing due to AEs [ Time Frame: Up to Week 50 ]
- Safety and tolerability as assessed by summary of suicide behavior and ideation risk as assessed by the electronic Columbia Suicide Severity Rating Scale (eC-SSRS) [ Time Frame: Up to Week 50 ]
- Safety and tolerability as assessed by summary of suicide behavior and ideation risk as assessed by Possible Suicidality Related Adverse Event (PSRAE) [ Time Frame: Up to Week 50 ]
- Safety and tolerability as assessed by change from baseline in clinical chemistry, hematology, and urinalysis parameters [ Time Frame: Up to Week 50 ]
- Safety and tolerability as assessed by frequency of clinical chemistry, hematology, and urinalysis parameters of potential clinical concern [ Time Frame: Up to Week 50 ]
- Safety and tolerability as assessed by change from baseline in blood pressure [ Time Frame: Up to Week 50 ]
- Safety and tolerability as assessed by change from baseline in heart rate [ Time Frame: Up to Week 50 ]
- Safety and tolerability as assessed by change from baseline in Electrocardiogram (ECG) parameters [ Time Frame: Up to Week 50 ]
- Safety and tolerability as assessed by frequency of vital signs and ECG parameters of potential clinical concern [ Time Frame: Up to Week 50 ]
- Trough concentration of GSK239512 at Week 4, Week 24, Week 36 and Week 48 [ Time Frame: Up to 48 weeks ]
- Sparse Pharmacokinetics (PK) sampling for concentration of GSK239512 at Week 8 [ Time Frame: Pre-dose, and 30 minutes (15 min to 1 hour), 2 hours (1 to 4 hours) and 6 hours (4 to 8 hours) post dose ]1 pre-dose and 3 post-dose samples. No samples should be collected within 30 minutes of the previous sample

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years to 50 Years (Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 18 to 50 years of age
- Diagnosed with a relapsing-remitting course of multiple sclerosis as defined by the appropriate McDonald criteria at the time of diagnosis.
- Diagnosis of RRMS made within approximately 10 years prior to the screening visit (as documented by year of diagnosis or duration of disease), and No physical manifestations of other forms of Multiple Sclerosis (MS) including signs of progression to secondary progressive MS (SPMS)
- Currently compliant with a stable dose regimen of Avonex (Interferon Beta1a) or Copaxone (Glatiramer Acetate) for management of MS for >= 1 year prior to the screening visit
- The occurrence of at least one of the following (within the year preceding the screen visit AND after >=2 months of stable treatment with Avonex OR Copaxone): a) 1 reported and/or documented relapse, OR b) 1 Gadolinium Enhanced (GdE) lesion on MRI
- Currently neurologically stable, in the investigator's judgment, and not actively experiencing or recovering from a recent relapse at the screening visit
- A Kurtzke Expanded Disability Status Scale (EDSS) score of 1 to 4.5 (inclusive) at the screening visit.
- Must agree not to participate in a clinical study involving another investigational drug or device throughout their participation in this study. Non-interventional study participation is allowed if the time involvement and scheduling will not interfere with compliance in this study in the opinion of the investigator
- A female subject is eligible to enter the study if she is a) Not pregnant or nursing, b) Of non-childbearing potential (i.e. women who have had a hysterectomy, are postmenopausal, which is defined as >2 years without menses [female subjects who have been post-menopausal for <2 years must be confirmed with Follicle Stimulating Hormone and estradiol levels], have both ovaries surgically removed or have current documented tubal ligation); or, c) Of childbearing potential and agrees to use the acceptable methods of birth control, for one month prior to the start of investigational product to 1 month after the last dose of investigational product.
- Informed Consent: Must be competent to understand the information given in the Institutional Review Board (IRB) or Independent Ethics Committee (IEC) approved Informed Consent Form (ICF) and must sign the form prior to the initiation of any study procedures
Exclusion Criteria:
- MRI: Unable to undergo MRI scans (e.g. due to pacemaker, severe claustrophobia, hypersensitivity to contrast media), Lacks adequate venous access for administration of Gd-enhancing agent, or Findings on brain MRI scan indicating any clinically significant brain abnormality other than MS (e.g. damage associated with prior traumatic brain injury)
- Past and Concurrent Medical Conditions: a) History of severe and clinically significant CNS trauma with current sequelae (e.g. traumatic brain injury, spinal cord compression), b) Significant concurrent, uncontrolled medical condition or disease which in the opinion of the investigator could (e.g. significant psychiatric disorder, etc), affect the subjects' safety, impair the subject's reliable participation in the trial, impair the evaluation of the endpoints, or necessitate the use of medication not allowed by this protocol, c) History or presence of myelopathy due to spinal cord compression by disk or vertebral disease or chronic progressive myelopathy, d) Diagnosis of any type epilepsy, e) At risk of suicide, as indicated by: A documented history of attempted suicide or significant suicidal ideation during the 6 months preceding the screening visit, OR If in the investigator's judgment the subject is at risk of a suicide attempt based on the screen visit assessment, including the eC-SSRS, f) Presence of significant and routine sleep disturbance (severe insomnia, nocturnal wandering, confusion, disorientation, agitation, or vivid dreams) that has a negative impact on quality of life that, in the judgement of the investigator, may increase the risk of tolerability issues during dose escalation, g) Presence or history of hallucinations that, in the judgement of the investigator, may increase the safety risk to the subject, h) Known diagnosis or history consistent with positive human immunodeficiency virus (HIV)
- Past and Current Medications and Therapies: Have had treatment with the following to manage their MS: a) Within 1 year: fingolimod (e.g. Gilenya), Rebif (interferon beta1a), interferon beta1b (e.g. Betaseron), mycophenolate mofetil (e.g. CellCept), or Recently approved medication or formulation indicated for the management of MS. Consult with GlaxoSmithKline (GSK) Medical Monitor if there are specific questions regarding eligible treatments b) Within 2 years: natalizumab (e.g. Tysabri), alemtuzumab (e.g. Campath), daclizumab (e.g. Zenapax), rituximab (e.g. Rituxan), mitoxantrone (e.g. Novantrone), cladribine (e.g. Leustatin), or azathioprine (e.g. Imuran)
- Have used corticotropin to manage a relapse within 6 months prior to Screen Visit.
- Have had treatment with the following and were unable to discontinue and refrain from treatment for the specified time period and are not able to discontinue use throughout participation in the clinical trial: dalfampridine /fampridine (e.g. Ampyra) - 1 month prior to Screen Visit, nabiximols (e.g. Sativex) - 1 month prior to Screen Visit, amantadine (e.g. Symmetrel) - 3 months prior to Screen Visit, or leflunomide (e.g. Arava) - 1 year prior to Screen Visit
- Have used the following medications within the last 30 days or 5 half-lives (whichever is longer) prior to screening and are not able to discontinue use throughout participation in the clinical trial: Any CNS stimulants (e.g., modafinil, dexamphetamine, methylphenidate), Known potent P-glycoprotein inhibitors (e.g. itraconazole, ketoconazole, cyclosporin, loperamide, diltiazem, verapamil, spironolactone, quinidine, bepridil, quinine, carvedilol), Known potent inhibitors or inducers of the CYP3A4 enzyme (e.g., verapamil, ketoconazole, cimetidine, rifampin, modafinil), CNS-penetrant antihistamines (e.g. bromopheniramine, chlorpheniramine, clemastine, diphenhydramine, hyrdoxyzine),
- History of medically significant adverse effects (including allergic reactions and hypersensitivities) following treatment with: Histamine H3 receptor antagonist or inverse agonist, Gadolinium enhancing agent, Relapse medication: glucocorticoids (e.g., methylprednisolone) OR A known hypersensitivity to components of the investigational product, relapse medication, or Gadolinium enhancing agent.
- Electrocardiogram (ECG) showing a clinically significant abnormality at screening. Including a QT interval corrected using Bazett's and Fridericia's formulas (QTcB or QTcF) interval of >=450 msec or >=480 msec for patients with a Bundle Branch Block.
- Infectious Disease Status at Screening a) Subjects with no documented record of vaccination against Hepatitis B (primary and secondary immunization and booster) AND a positive test for hepatitis B surface antigen (HBsAg and Hepatitis B Core Antibody [IgM anti-HBc]), b) Subjects with serologic evidence of active Hepatitis C, as indicated by a positive Hepatitis C Virus(HCV) RNA test and anti-HCV antibody test
- Laboratory Values at Screening: Hematology: Total white cell count <2.0 x 109/L, Neutrophils <1.0 x 109/L, Platelets <75 x 109/L (If out of range, platelet count can be repeated to exclude platelet clumping), or Haemoglobin < 80 g/L.
- Screening clinical chemistry liver function test: Alanine aminotransferase (ALT) >2.0 x upper limit of normal (ULN), Aspartate aminotransferase (AST) >2.0 x ULN, Alkaline phosphatise (ALP) >1.5 x ULN, or Bilirubin >1.5 x ULN.
- Documented renal insufficiency or laboratory results indicative of renal insufficiency (due to risks associated with administration of Gadolinium based contrast agents to subjects with moderate to severe kidney disease): Estimated Creatinine Clearance (Cockroft-Gault) <60 mL/minute
- If known, or according to investigator judgement, subject is suspected of not being able to comply with the study protocol requirements. Contributing factors to this assessment by the investigator could be, but not limited to: job demands, substance abuse, alcoholism, drug dependency or psychological disorder
- Prior participation in a clinical trial or use of an investigational product for a non approved intervention: Prior use of an investigational drug for MS or a condition other than MS within 4 weeks or 5 half-lives (whichever is longer) prior to screening. The GSK Medical Monitor should be consulted to confirm eligibility

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01772199
Bulgaria | |
GSK Investigational Site | |
Sofia, Bulgaria, 1113 | |
GSK Investigational Site | |
Sofia, Bulgaria, 1309 | |
GSK Investigational Site | |
Sofia, Bulgaria, 1431 | |
Canada, Alberta | |
GSK Investigational Site | |
Calgary, Alberta, Canada, T2N 2T9 | |
GSK Investigational Site | |
Edmonton, Alberta, Canada, T6G 1Z1 | |
Canada, Ontario | |
GSK Investigational Site | |
Ottawa, Ontario, Canada, K1H 8L6 | |
Canada, Quebec | |
GSK Investigational Site | |
Gatineau, Quebec, Canada, J9J 0A5 | |
GSK Investigational Site | |
Montreal, Quebec, Canada, H3A 2B4 | |
Czech Republic | |
GSK Investigational Site | |
Jihlava, Czech Republic, 586 33 | |
GSK Investigational Site | |
Olomouc, Czech Republic, 775 20 | |
GSK Investigational Site | |
Teplice, Czech Republic, 415 29 | |
Germany | |
GSK Investigational Site | |
Ulm, Baden-Wuerttemberg, Germany, 89073 | |
GSK Investigational Site | |
Alzenau, Bayern, Germany, 63755 | |
GSK Investigational Site | |
Unterhaching, Bayern, Germany, 82008 | |
GSK Investigational Site | |
Koeln, Nordrhein-Westfalen, Germany, 50935 | |
GSK Investigational Site | |
Muenster, Nordrhein-Westfalen, Germany, 48149 | |
GSK Investigational Site | |
Dresden, Sachsen, Germany, 01069 | |
GSK Investigational Site | |
Leipzig, Sachsen, Germany, 04103 | |
GSK Investigational Site | |
Berlin, Germany, 10961 | |
GSK Investigational Site | |
Berlin, Germany, 12163 | |
GSK Investigational Site | |
Hamburg, Germany, 20249 | |
GSK Investigational Site | |
Hamburg, Germany, 22083 | |
Spain | |
GSK Investigational Site | |
Barcelona, Spain, 08035 | |
GSK Investigational Site | |
Barcelona, Spain, 08036 | |
GSK Investigational Site | |
Madrid, Spain, 28034 | |
GSK Investigational Site | |
Madrid, Spain, 28040 | |
GSK Investigational Site | |
Madrid, Spain, 28046 | |
GSK Investigational Site | |
Majadahonda (Madrid), Spain, 28222 | |
GSK Investigational Site | |
Malaga, Spain, 29010 | |
GSK Investigational Site | |
Sevilla, Spain, 41009 | |
Sweden | |
GSK Investigational Site | |
Stockholm, Sweden, SE-141 86 | |
Ukraine | |
GSK Investigational Site | |
Donetsk, Ukraine, 83099 | |
GSK Investigational Site | |
Ivano-Frankivsk, Ukraine, 76008 | |
GSK Investigational Site | |
Kharkiv, Ukraine, 61068 | |
GSK Investigational Site | |
Kyiv, Ukraine, 04107 | |
GSK Investigational Site | |
Lutsk, Ukraine, 43005 | |
GSK Investigational Site | |
Lviv, Ukraine, 79010 | |
GSK Investigational Site | |
Poltava, Ukraine, 36024 | |
GSK Investigational Site | |
Vinnitsa, Ukraine, 21005 | |
United Kingdom | |
GSK Investigational Site | |
London, United Kingdom, NW1 2BU | |
GSK Investigational Site | |
London, United Kingdom, SE5 9RS | |
GSK Investigational Site | |
Romford, United Kingdom, RM7 0AG | |
GSK Investigational Site | |
Sheffield, United Kingdom, S10 2JF |
Study Director: | GSK Clinical Trials | GlaxoSmithKline |
Study Data/Documents: Individual Participant Data Set

For additional information about this study please refer to the GSK Clinical Study Register

For additional information about this study please refer to the GSK Clinical Study Register

For additional information about this study please refer to the GSK Clinical Study Register

For additional information about this study please refer to the GSK Clinical Study Register

For additional information about this study please refer to the GSK Clinical Study Register

For additional information about this study please refer to the GSK Clinical Study Register

For additional information about this study please refer to the GSK Clinical Study Register
Responsible Party: | GlaxoSmithKline |
ClinicalTrials.gov Identifier: | NCT01772199 |
Other Study ID Numbers: |
116477 |
First Posted: | January 21, 2013 Key Record Dates |
Last Update Posted: | August 16, 2016 |
Last Verified: | August 2016 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
Plan Description: | Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site. |
GSK239512 remyelination magnetic resonance imaging |
Relapsing Remitting Multiple Sclerosis Histamine 3 Receptor Antagonist magnetization transfer ratio |
Multiple Sclerosis Multiple Sclerosis, Relapsing-Remitting Sclerosis Pathologic Processes Demyelinating Autoimmune Diseases, CNS |
Autoimmune Diseases of the Nervous System Nervous System Diseases Demyelinating Diseases Autoimmune Diseases Immune System Diseases |