Multiple Sclerosis, Relapsing-RemittingPhase 2NCT01772199
Study to Assess Whether GSK239512 Can Remyelinate Lesions in Subjects With Relapsing Remitting Multiple Sclerosis
A Phase 2 study testing GSK239512 in people with Multiple Sclerosis, Relapsing-Remitting, run by GlaxoSmithKline at 43 sites in 8 countries.
Trial summary
This is a randomized, parallel group, placebo-controlled study designed to assess whether GSK239512 can enhance lesion remyelination in subjects with Relapsing Remitting Multiple Sclerosis (RRMS). Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Multiple Sclerosis, Relapsing-Remitting
- What is being tested?
- GSK239512
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 131 participants
- Where
- 43 sitesin 8 countries
- Study dates
- Feb 2013to Sep 2014
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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),
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- 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
Trial locations and contacts
43 sites in 8 countries.
43 sites in 8 countries
Germany11 sites
GSK Investigational Site
Alzenau in Unterfranken, Bavaria, 63755
GSK Investigational Site
Berlin, State of Berlin, 10961
GSK Investigational Site
Berlin, State of Berlin, 12163
GSK Investigational Site
Cologne, North Rhine-Westphalia, 50935
GSK Investigational Site
Dresden, Saxony, 01069
GSK Investigational Site
Hamburg, Free and Hanseatic City of Hamburg, 20249
GSK Investigational Site
Hamburg, Free and Hanseatic City of Hamburg, 22083
GSK Investigational Site
Leipzig, Saxony, 04103
GSK Investigational Site
Münster, North Rhine-Westphalia, 48149
GSK Investigational Site
Ulm, Baden-Wurttemberg, 89073
GSK Investigational Site
Unterhaching, Bavaria, 82008
Spain8 sites
GSK Investigational Site
Barcelona, 08035
GSK Investigational Site
Barcelona, 08036
GSK Investigational Site
Madrid, 28034
GSK Investigational Site
Madrid, 28040
GSK Investigational Site
Madrid, 28046
GSK Investigational Site
Majadahonda (Madrid), 28222
GSK Investigational Site
Málaga, 29010
GSK Investigational Site
Seville, 41009
Ukraine8 sites
GSK Investigational Site
Donetsk, 83099
GSK Investigational Site
Ivano-Frankivsk, 76008
GSK Investigational Site
Kharkiv, 61068
GSK Investigational Site
Kyiv, 04107
GSK Investigational Site
Lutsk, 43005
GSK Investigational Site
Lviv, 79010
GSK Investigational Site
Poltava, 36024
GSK Investigational Site
Vinnitsa, 21005
Canada5 sites
GSK Investigational Site
Calgary, Alberta, T2N 2T9
GSK Investigational Site
Edmonton, Alberta, T6G 1Z1
GSK Investigational Site
Gatineau, Quebec, J9J 0A5
GSK Investigational Site
Montreal, Quebec, H3A 2B4
GSK Investigational Site
Ottawa, Ontario, K1H 8L6
United Kingdom4 sites
GSK Investigational Site
London, NW1 2BU
GSK Investigational Site
London, SE5 9RS
GSK Investigational Site
Romford, RM7 0AG
GSK Investigational Site
Sheffield, S10 2JF
Bulgaria3 sites
GSK Investigational Site
Sofia, 1113
GSK Investigational Site
Sofia, 1309
GSK Investigational Site
Sofia, 1431
Czechia3 sites
GSK Investigational Site
Jihlava, 586 33
GSK Investigational Site
Olomouc, 775 20
GSK Investigational Site
Teplice, 415 29
About this study
Official title: Proof of Mechanism Study to Assess the Potential of GSK239512 to Remyelinate Lesions in Subjects With Relapsing Remitting Multiple Sclerosis
This is a randomized, parallel group, placebo-controlled study designed to assess whether GSK239512 can enhance lesion remyelination in subjects with Relapsing Remitting Multiple Sclerosis (RRMS). Subjects with RRMS on stable background treatment with either Avonex (Interferon-beta1a) or Copaxone (Glatiramer Acetate) are eligible to participate. Subjects will be randomized in a 1:1 ratio between placebo and GSK239512, and will continue to be managed with their current standard of care therapy (Copaxone or Avonex). The total treatment period is 48 weeks, including a standard 4 week titration period and 44 week maintenance treatment period (which could be adapted to a 5-week titration and 43 week maintenance period, if needed). Titration doses start at 10 micrograms (mcg) and increase up to 80 mcg (10 mcg first week, 20 mcg second week, 40 mcg third week, 80 mcg fourth week). Subjects will be titrated to the maximum tolerated dose with the objective of titrating to the highest dose (80 mcg GSK239512), whenever possible, based on investigator judgement of tolerability. The post-treatment follow-up period will be a minimum of 2 weeks in duration following the end of treatment at Week 48 or early withdrawal, as appropriate.
- Conditions
- Multiple Sclerosis, Relapsing-Remitting
- Being tested
- GSK239512, Placebo
- Keywords
- GSK239512, remyelination, magnetic resonance imaging, Relapsing Remitting Multiple Sclerosis, Histamine 3 Receptor Antagonist, magnetization transfer ratio
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK239512Drug
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
PlaceboDrug
White to almost white, round tablets. Once daily orally.
| Study group | Role | What they receive |
|---|---|---|
| GSK239512 Arm | Experimental | 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 Receives: Drug: GSK239512 |
| Placebo Arm | Placebo comparator | Placebo once daily orally Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
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
Measured: Up to Week 48
Mean change in Delta MTR lesion MTR differences (calibrated to reference scan) from before lesion appearance to stable recovery (>=3 months post lesion appearance)
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
Measured: Up to Week 48
Secondary outcomes (23)
Change from baseline in T2 lesion MTR at Week 48
Measured: Baseline and Week 48
Cumulative new and enlarging Gd enhancing, T2 and Combined Unique Active lesions comparing placebo to GSK239512 treated subjects
Measured: 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
Measured: 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
Measured: 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
Measured: Up to Week 48
Mean change from baseline in overall cognitive impairment and cognitive domains comparing placebo to GSK239512 treated subjects
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
Measured: Baseline and Week 48
Comparison of Relapse Rates between placebo and GSK239512 treated subjects
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
Measured: Up to 50 Weeks
Comparison of Time to First Relapse between placebo and GSK239512
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
Measured: Up to 50 Weeks
Comparison of the proportion of subjects Relapse Free between placebo and GSK239512 treated subjects
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
Measured: Up to 50 Weeks
Proportion of subjects with sustained worsening of Expanded Disability Severity Scale (EDSS) over 3 months comparing placebo to GSK239512 treated subjects
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
Measured: Up to 48 Weeks
Mean change from baseline in the EDSS functional systems and a subset of component assessments comparing placebo to GSK239512 treated subjects
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
Measured: Up to 48 Weeks
Safety and tolerability as assessed by frequency and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Measured: Up to Week 50
Safety and tolerability as assessed by percentage of subjects withdrawing due to AEs
Measured: 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)
Measured: 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)
Measured: Up to Week 50
Safety and tolerability as assessed by change from baseline in clinical chemistry, hematology, and urinalysis parameters
Measured: Up to Week 50
Safety and tolerability as assessed by frequency of clinical chemistry, hematology, and urinalysis parameters of potential clinical concern
Measured: Up to Week 50
Safety and tolerability as assessed by change from baseline in blood pressure
Measured: Up to Week 50
Safety and tolerability as assessed by change from baseline in heart rate
Measured: Up to Week 50
Safety and tolerability as assessed by change from baseline in Electrocardiogram (ECG) parameters
Measured: Up to Week 50
Safety and tolerability as assessed by frequency of vital signs and ECG parameters of potential clinical concern
Measured: Up to Week 50
Trough concentration of GSK239512 at Week 4, Week 24, Week 36 and Week 48
Measured: Up to 48 weeks
Sparse Pharmacokinetics (PK) sampling for concentration of GSK239512 at Week 8
1 pre-dose and 3 post-dose samples. No samples should be collected within 30 minutes of the previous sample
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jan 2013 (estimated)
- Study startFeb 2013
- Primary completionSep 2014
- Study completionSep 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple Sclerosis, Relapsing-RemittingStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 131 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01772199
- Sponsor's protocol ID
- 116477
- Status last verified
- Aug 2016
- First submitted
- 17 Jan 2013
- Last updated
- 16 Aug 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Study at a glance
From the registry record, last updated by the sponsor on 16 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Proof of Mechanism Study to Assess the Potential of GSK239512 to Remyelinate Lesions in Subjects With Relapsing Remitting Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT01772199
- Acronym / sponsor ID
- 116477
- Conditions
- Multiple Sclerosis, Relapsing-Remitting
- Keywords
- GSK239512, remyelination, magnetic resonance imaging, Relapsing Remitting Multiple Sclerosis, Histamine 3 Receptor Antagonist, magnetization transfer ratio
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 131 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- Feb 2013
- Primary completion
- Sep 2014 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 21 Jan 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a randomized, parallel group, placebo-controlled study designed to assess whether GSK239512 can enhance lesion remyelination in subjects with Relapsing Remitting Multiple Sclerosis (RRMS). Subjects with RRMS on stable background treatment with either Avonex (Interferon-beta1a) or Copaxone (Glatiramer Acetate) are eligible to participate. Subjects will be randomized in a 1:1 ratio between placebo and GSK239512, and will continue to be managed with their current standard of care therapy (Copaxone or Avonex). The total treatment period is 48 weeks, including a standard 4 week titration period and 44 week maintenance treatment period (which could be adapted to a 5-week titration and 43 week maintenance period, if needed). Titration doses start at 10 micrograms (mcg) and increase up to 80 mcg (10 mcg first week, 20 mcg second week, 40 mcg third week, 80 mcg fourth week). Subjects will be titrated to the maximum tolerated dose with the objective of titrating to the highest dose (80 mcg GSK239512), whenever possible, based on investigator judgement of tolerability. The post-treatment follow-up period will be a minimum of 2 weeks in duration following the end of treatment at Week 48 or early withdrawal, as appropriate.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| GSK239512 Arm | Experimental | Drug: GSK239512GSK239512 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 Arm | Placebo comparator | Drug: PlaceboPlacebo once daily orally |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (14 listed)
- 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
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 |
|---|---|---|
| GSK239512White 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 | Drug | GSK239512 Arm |
| PlaceboWhite to almost white, round tablets. Once daily orally. | Drug | Placebo Arm |
Primary outcome
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
23 secondary outcomes
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
Comparison of Relapse Rates between placebo and GSK239512 treated subjects
Time frame: Up to 50 Weeks
Comparison of Time to First Relapse between placebo and GSK239512
Time frame: Up to 50 Weeks
Comparison of the proportion of subjects Relapse Free between placebo and GSK239512 treated subjects
Time frame: Up to 50 Weeks
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
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Aug 2016.
- Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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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.
GSK Clinical Trials study director
GlaxoSmithKline
43 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GSK239512 in people with Multiple Sclerosis, Relapsing-Remitting, run by GlaxoSmithKline at 43 sites in 8 countries.
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 10 inclusion and 14 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 16 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 43 sites in Germany, Spain, Ukraine, Canada, United Kingdom and 3 more countries. 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 phase mean?
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 Aug 2016.