E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsing-Remitting Multiple Sclerosis |
ustępująco-nawracająca postać stwardnienia rozsianego |
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E.1.1.1 | Medical condition in easily understood language |
Multiple Sclerosis |
stwardnienie rozsiane |
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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 | 20.0 |
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 |
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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 |
Evaluate the safety of ALKS 8700 and the GI tolerability of ALKS 8700 and DMF in adult subjects with RRMS |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Capable of understanding and complying with the protocol
2. Male and female adults aged 18 to 65 years, inclusive
3. Has a confirmed diagnosis of RRMS
4. Neurologically stable with no evidence of relapse within 30 days prior to randomization (Visit 3)
5. Agrees to use an acceptable method of contraception for the duration of the study and for 30 days after any study drug administration or is surgically sterile or post-menopausal
6. Additional criteria may apply |
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E.4 | Principal exclusion criteria |
1. Have any finding(s) that would compromise the safety of the subject, affect the subject’s ability to adhere to the protocol visit schedule or to fulfill visit requirements, or would make the subject unsuitable for participation in the study
2. Diagnosis of primary progressive, secondary progressive, or progressive relapsing MS
3. History of clinically significant cardiovascular, pulmonary, gastrointestinal, dermatologic, psychiatric, neurologic (other than MS), endocrine, renal and/or other major disease that would preclude participation in a clinical trial
4. History of GI surgery (except appendectomy that occurred more than 6 months prior to screening; other prior surgeries may be permitted based on Medical Monitor approval)
5. History of clinically significant recurring or active gastrointestinal symptoms within 3 months of screening
6. Chronic use (≥7 days) of medical therapy to treat any GI symptoms within 1 month of screening
7. Has a clinically significant medical condition or observed abnormality at screening
8. History of a myocardial infarction, including a silent myocardial infarction identified on ECG, or unstable angina
9. History of clinically significant drug or alcohol abuse within the past year prior to screening
10. Any of the following abnormal blood tests at screening (Visit 1):
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥2 times the upper limit of normal (ULN)
• Thyroid-stimulating hormone (TSH) level higher than the ULN by 10% or more at screening
• Estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73m2 (using the CKD EPI equation; (Levey, Stevens et al. 2009)
• Lymphocyte count <0.9 x 103/μL
11. Any of the following abnormal urine tests at screening (Visit 1):
• Beta-2 microglobulin >0.3 μg/mL
• Albumin to creatinine ratio >200 mg/g
12. Clinically significant history of suicidal ideation or suicidal behavior in the last 12 months
13. Subject is pregnant or breastfeeding or plans to become pregnant or begin breastfeeding at any point during the study and for 30 days after any study drug administration
14. Steroids, with the exception of topical or inhaled steroids, or IV
immunoglobulin within 30 days prior to randomization (Visit 3)
15. Prior treatment with Fumaderm or Tecfidera
16. Additional criteria may apply |
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E.5 End points |
E.5.1 | Primary end point(s) |
The number of days with any IGISIS individual symptom intensity score ≥2 relative to exposure days in Part A and Part B. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. Number of days with any IGISIS individual symptom intensity score ≥2 relative to exposure days in Part B
2. Number of days with any IGISIS individual symptom intensity score ≥1 relative to exposure days in Part A and Part B
3. Number of days with any IGISIS individual symptom intensity score ≥3 relative to exposure days in Part A and Part B
4. Number of days with a GGISIS symptom intensity score ≥1 relative to exposure days in Part A and Part B
5. Number of days with a GGISIS symptom intensity score ≥2 relative to exposure days in Part A and Part B
6. Number of days with a GGISIS symptom intensity score ≥3 relative to exposure days in Part A and Part B
7. Worst IGISIS individual symptom intensity score by week during the 5 week treatment period in Part A and Part B
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | 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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | No |
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 | No |
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 |
Germany |
Poland |
United States |
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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
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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 | 7 |
E.8.9.1 | In the Member State concerned days | 12 |
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 | 10 |