E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 11.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028245 |
E.1.2 | Term | <Manually entered code. Term in E.1.1> |
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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 the activity of nerispirdine in improving ability to walk, defined as a consistent improvement in walking speed as measured by the Timed 25-Foot Walk (T25-FW) in patients with MS. |
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E.2.2 | Secondary objectives of the trial |
•To assess other measures of efficacy such as the MSWS-12, MFIS, LEMMT, MAS, SGI, and CGI •To assess the safety and tolerability of nerispirdine •To evaluate the pharmacokinetic (PK) parameters of nerispirdine and its active metabolite, HP183 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Clinically definite MS (McDonald criteria), which includes patients with remitting-relapsing, secondary progressive, progressive-relapsing, or primary progressive MS AND walking disability due to MS (untreated or treated with a stable regimen of a marketed compound for treatment of MS, limited to beta interferons or glatiramer acetate). MS type (relapsing-remitting, secondary progressive, primary progressive, or progressive relapsing) will be determined by the Investigator based on the AAN Practice Guidelines and Tools (http://www.aan.com/go/practice/guidelines) and reference 1 provided in the protocol. 2. Signed Informed Consent form |
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E.4 | Principal exclusion criteria |
Methodology-related 1. Patient who is able to walk 25 feet in less than 8 seconds or subject who takes more than 45 seconds (for any of the 2 allowed trials) to walk 25 feet with or without an assistive device during the T25-FW assessment at V1-V4 (before randomization). Patients without valid V1, V2, and V4 T25-FW measurements are not eligible for randomization. 2. Multiple sclerosis exacerbation or clinical relapse within 6 months prior to the screening visit (V1) or change in regimen or type of MS treatment during the last 3 months, or start of MS disease-modifying therapies within the 3 months prior to screening. 3. Age <18 years 4. Patients who participated in any previous nerispirdine (HP184) trials 5. Patients who were previously exposed to 3,4-diaminopyridine or 4-aminopyridine (4-AP, fampridine, Fampridine-SR) 6. Patients with current active psychiatric disorders including but not limited to active psychosis, exacerbation of schizophrenia, bipolar disorder, obsessive-compulsive disorder, major depressive disorder, anxiety disorder, and alcohol or substance abuse or dependence (except nicotine) 7. Use of any investigational drug within 30 days or 5 half-lives whichever is longer 8. Patient is the Investigator or any Subinvestigator, Research Assistant, Pharmacist, Study Coordinator, other staff or relative thereof directly involved in the conduct of the protocol/study 9. Patients who are unable to participate for the entire duration of the study, or in the opinion of the Investigator, are likely to be non-compliant with the obligations inherent in the clinical trial participation 10. Any clinically meaningful or unexplained laboratory abnormality(ies); clinically significant or unstable condition(s) or comorbidities; acute or chronically progressive medical or surgical disorder(s) other than MS which may interfere with walking and may affect patient safety (see Appendix L of the protocol) Patients with confirmed neutropenia (neutrophils < 1500/mm3 or according to ethnic group), thrombocytopenia (platelets < 100 000/ mm3), increase in aminotransferases (either ALT [SGPT] or AST [SGOT] >3 ULN and CPK normal) or creatinine clearance < 50 mL/min cannot be randomized (see Appendix L specifying criteria for discontinuation of IP).
-Nerispirdine-related based on current knowledge on the compound 11. Criteria to reduce reproductive risk: Breastfeeding and pregnant females cannot be included in a clinical study testing nerispirdine. Male subjects who are sexually active with a pregnant female should not participate in the study. Also, patients wishing to breastfeed or parent a child during the course of the study must not participate. Women of childbearing potential (WOCBP) as defined in the protocol or male patients not using an effective contraceptive method as described in the protocol cannot be included in clinical studies testing nerispirdine. Women of childbearing potential, who are unwilling to or unable to be tested for pregnancy at study entry and at each clinic visit, or who experience an unexpected delay of menses cannot participate in the study. The pregnancy test to be used in this study is a serum pregnancy test (β-HCG), and not an urine pregnancy test. This test will be performed at each visit. If, during any nerispirdine study, a female subject becomes pregnant or decides to attempt to become pregnant or if a male subject decides to attempt to father a child, then she or he must stop the study drug immediately. If a female subject becomes pregnant during the study, then the Investigator must work with sanofi-aventis to deliver appropriate reporting, and follow up as per the study protocol and ICH guidelines. “Women NOT of Child Bearing Potential,” as defined in the protocol, do not have to use any method of contraception during a study. Women of childbearing potential willing to participate in the study must agree that they will take means to reduce reproductive risk up to 2 weeks after the end of treatment, by agreeing to use a double (dual) method of contraception as needed and described in the protocol. Male subjects willing to participate in the study must agree that they will take means to reduce reproductive risk up to 2 weeks after the end of treatment, by agreeing to use a double (dual) method of contraception, as needed and described in the protocol, and to reduce risk to potentially expose fetus to the drug through vaginal absorption. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Responder criterion, based on consistency of improved response in walking speed on the T25-FW A responder is defined as one whose last T25-FW measurement on-treatment and at least 2 other T25-FW measurement on-treatment are faster than the fastest speed recorded during any of the 3 “off drug” visits V2 to V4 before double-blind treatment and the 1 at the end of the 2-week placebo run-out period. All other randomized patients are defined as non-responders. |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 22 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 5 |