E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsing-remitting multiple sclerosis |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10063399 |
E.1.2 | Term | Relapsing-remitting multiple sclerosis |
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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 of this study is to evaluate the efficacy of PI-2301 by magnetic resonance imaging (MRI), as measured by the sum of the number of total gadolinium-enhancing lesions on serial T1-weighted MRI brain scans at Weeks 24 (Visit 9) through 40 (Visit 13) from 2 dose levels of PI-2301 (3 mg and 10 mg) as compared to placebo, in subjects with relapsing remitting multiple sclerosis (RR-MS) when administered study drug weekly for 40 weeks. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effect of two different doses (3 mg and 10 mg) of PI-2301 as compared to placebo on the following parameters: - The sum of the number of new gadolinium-enhancing lesions on T1 weighted MRI brain scans at Weeks 24 through 40. - Other MRI markers of lesion activity and burden - Brain atrophy - Annualized Relapse Rate - Week 12 safety as per MRI scans - Safety and tolerability of PI-2301 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female, between the ages of 18 and 55 years (inclusive). 2. Subject is willing and able to comply with the protocol requirements, has gone through the consent process, and has signed an approved informed consent form. 3. Subject is able to learn and self-administer subcutaneous injections (a care-giver may be trained to inject the subject). 4. Patients must have a current diagnosis of RR-MS according to the 2005 revised McDonald MS diagnostic criteria. 5. Subject must have at least one (and may meet 2 or 3 of these criteria) of the following: • Documented history of 2 MS relapses during the 2 years prior to Screening Visit 1. OR • Documented history of 1 MS relapse in the year prior to Screening Visit 1. OR • Evidence of at least one gadolinium-enhancing lesion on the Screening MRI (T1 weighted imaging with gadolinium contrast) using a 1.5 or 3.0 Tesla magnet. (MRI magnet strength should be the same for all subjects at a clinical site for all MRI visits and preferably the same MRI machine is used over the course of the trial.) 6. EDSS score of 0-5.5. 7. Female subjects of both childbearing potential and non-childbearing potential may be included, unless the local regulatory authority requires that only women of non-childbearing potential be included. All women of childbearing potential (WOCBP) must test negative for enrollment based on a serum pregnancy test and agree to use a highly reliable method of birth control (such as use of oral contraceptives or Norplant ®; a reliable barrier method i.e. diaphragms with contraceptive jelly; cervical caps with contraceptive jelly; condoms with contraceptive foam; intrauterine devices; partners with vasectomy or abstinence) beginning at least 14 days prior to Screening Visit 1 and continuing throughout the study to End of Study (EOS) Visit 14. WOCBP must not be planning to become pregnant while enrolled in this study. Non-childbearing potential is defined as one of the following: • Post-menopausal, defined as amenorrheic (complete cessation of menstruation) for at least 1 year. • A documented hysterectomy, bilateral oophorectomy or bilateral tubal ligation at least 6 months prior to study initiation. 8. With the exception of signs and symptoms that directly relate to their MS, subjects must be in good general health, per Investigator opinion, without unstable medical conditions, significant physical examination findings, or clinically significant abnormal laboratory results. 9. Subjects must have a negative urine screen for alcohol and drugs of abuse at the Screening Visit 1, unless either opiates or cannaboids were prescribed or recommended by a physician. |
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E.4 | Principal exclusion criteria |
1. Any MS categorized as secondary progressive (SP), primary progressive (PP), or progressive relapsing (PR). 2. Any relapse of MS within 30 days of Screening Visit 1 or Baseline Visit 2 or a relapse which has not stabilized. 3. Greater than 20 gadolinium-enhancing lesions on the Screening MRI scan. 4. Systemic glucocorticoid therapy, beta interferon-1a or beta interferon-1b therapy within 30 days of Screening Visit 1 or Baseline Visit 2. 5. Allergy to mannitol. 6. Treatment with azathioprine, cyclosporine or methotrexate within 3 months of Screening Visit 1. 7. Any prior administration of Copaxone® (glatiramer acetate), any biosimilar to Copaxone, Tysabri (natalizumab), Rituxan (rituximab) or history of total lymphoid irradiation. 8. Treatment with cladribine, Cellcept (mycophenolate mofetil), fingolimod, (FTY720), BG-12 (fumarate), Zenapax (daclizumab), laquinimod, teriflunomide, ustekinumab, mitoxantrone, cyclosphosphamide, Campath (alemtuzumab), dirucotide, BHT-3009 within one year of Screening Visit 1. 9. Known to be seropositive for Human Immunodeficiency Virus (HIV) or with known immunosuppression due to acquired immunodeficiency syndrome (AIDS) or other etiology of immunosuppression. 10. Positive serology result for Hepatitis B surface antigen (HbsAg) or anti-Hepatitis C antibody (anti-HCV). 11. History of alcoholism, or of abuse of alcohol. 12. Current or within past 5 years, history of malignancy other than successfully treated squamous or basal cell carcinoma of the skin, or successfully treated in situ cervical cancer. 13. History of clinically unstable gastrointestinal, renal, hepatic, endocrine, pulmonary or cardiovascular disease; or a history of tuberculosis, epilepsy, diabetes, psychosis, glaucoma; or any other condition, which in the opinion of the Investigator, would jeopardize the safety of the subject or impact the validity of the study results. 14. Clinically significant abnormality on screening or baseline electrocardiograms (ECGs) or clinical laboratory results. 15. Subject is pregnant or breastfeeding. Women must have a negative serum beta-human chorionic gonadotropin (β-HCG) at screening (Visit 1) and a negative urine pregnancy test prior to randomization and the first dose of study medication at Visit 2 Week 1. 16. Contraindications for MRI, including but not limited to, a pacemaker, contrast allergy to gadolinium, impaired renal function contraindicating contrast administration, or inadequately treated claustrophobia making MRI examination unsuitable. 17. Participation in a previous investigational drug or device study within 30 days preceding Screening Visit 1. |
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E.5 End points |
E.5.1 | Primary end point(s) |
MRI: The sum of the total number of gadolinium-enhancing lesions on T1-weighted MRI brain scans at Weeks 24, 28, 32, 36 and 40. |
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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 | Yes |
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 | 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 | 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) | Yes |
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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 78 |
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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last visit of the last subject |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |