E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsing Remitting Multiple Sclerosis |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10063399 |
E.1.2 | Term | Relapsing-remitting multiple sclerosis |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to assess whether treatment with raltegravir in patients with active MS has the effect of reducing the total number or rate of development of new or recurrent Gd-enhanced lesions on brain MRI over the period of treatment, compared to baseline. |
|
E.2.2 | Secondary objectives of the trial |
1. Demonstrate a reduction in the cumulative number of new or enlarging T2 weighted lesions on brain MRI over the period of treatment with Raltegravir compared with baseline. 2. Assess other MRI parameters of disease activity e.g. cumulative number of T2 lesions, cumulative number of Gd-T1 enhancing lesions, and percent of subjects with scans free from enhancing lesions in Raltegravir treated subjects vs. baseline. 3. Determine the effect of raltegravir therapy on specific inflammatory markers of MS activity. 4. Determine the effect of raltegravir on specific indicators of endogenous retroviral activity and activity of herpes viruses. 5. Explore preliminary clinical responses in relapsing-remitting multiple sclerosis subjects treated with Raltegravir, compared with baseline as measured by: a) Multiple Sclerosis Functional Composite (MSFC) b) Kurtzke Extended Disability Status Scale (EDSS) c) Multiple Sclerosis Quality of Life Inventory (MSQLI)
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients between 18-55 years of age. • Diagnosis of MS, according to the revised McDonald Criteria 2010. • EDSS score of 0-6.0 inclusive. • Documented at least one relapse within the past 12 months or at least one Gd-enhanced lesion on the brain MRI. detected within 3 months prior to screening date • Gd-enhanced lesion on screening MRI if MRI not used to meet screening criteria above. • Female patients of childbearing potential will be expected to be on appropriate contraception (hormonal or barrier method of birth control; abstinence) from time of consent until 6 weeks after treatment discontinuation. (the repeated administration of gadolinium and MRI are not recommended during pregnancy). NOTE: Subjects are considered not of child bearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal. • Females of childbearing potential must have a negative urine pregnancy test prior to every MRI scan/ within 7 days prior to being registered for protocol therapy. • Must give written informed consent and authorize the release and use of protected health information, as required by local law. • Able and willing to undergo blood, saliva and urine sampling at regular intervals as defined by the protocol. • Able and willing to receive Gadolinium enhanced MRI’s at regular intervals as defined by the protocol. • Able to comply with study requirements. |
|
E.4 | Principal exclusion criteria |
• Pregnant or breastfeeding or unwilling to use contraception. • Treatment with immunosuppressive, immunomodulatory or experimental treatments within the last 6 months of enrolment in the study, but excluding pulsed intravenous or oral steroids for treatment of MS relapse. • No pulsed intravenous or oral steroids in the 30 days preceding the baseline assessment. • Patients presenting with medical disorder deemed severe or unstable by the CI such as poorly controlled diabetes or arterial hypertension, severe cardiac insufficiency, unstable ischemic heart disease, abnormal liver function tests (>2.5 times ULN) and abnormal complete blood count (in particular leukopenia, as defined by a lymphocyte count <500, neutrophil <1.5 or platelet count < 100, or thrombocytopenia < 1.5 LLN), or any medical condition which, in the opinion of the chief investigator, would pose additional risk to the patient. • Presence of human immunodeficiency virus antibodies. • Patients receiving proton pump inhibitors (e.g. omeprazole/esomeprazole) • Patients with active hepatitis B or/and C with liver function tests >2.5 times ULN • Exposure to any other investigational drug within 30 days of enrolment in the study. • Prior history of malignancy unless an exception is granted by the Chief Investigator. • History of uncontrolled drug or alcohol abuse within 6 months prior to enrolment into the study. • Patients treated with Rifampicin in past four weeks. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The number of new or recurrent Gd-enhancing lesions that appear on brain T1-weighted MRI over the period of treatment with raltegravir, compared to baseline. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
This endpoint will be measured and baseline and then every 4 weeks for the duration of the trial. |
|
E.5.2 | Secondary end point(s) |
1. Demonstrate a reduction in the cumulative number of new or enlarging T2 weighted lesions on brain MRI over the period of treatment with Raltegravir compared with baseline. 2. Assess other MRI parameters of disease activity e.g. cumulative number of T2 lesions, cumulative number of Gd-T1 enhancing lesions, and percent of subjects with scans free from enhancing lesions in Raltegravir treated subjects vs. baseline. 3. Determine the effect of raltegravir therapy on specific inflammatory markers of MS activity. 4. Determine the effect of raltegravir on specific indicators of endogenous retroviral activity and activity of herpes viruses. 5. Explore preliminary clinical responses in relapsing-remitting multiple sclerosis subjects treated with Raltegravir, compared with baseline as measured by: a) Multiple Sclerosis Functional Composite (MSFC) b) Kurtzke Extended Disability Status Scale (EDSS) c) Multiple Sclerosis Quality of Life Inventory (MSQLI) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Gd-enhanced MRI's and blood tests to collect data for the secondary endpoints will be carried out at baseline and then every 4 weeks for the duration of the trial |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
End of trial is determinded as Last Patient Last Visit |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |