E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Episodic and Chronic Migraine |
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E.1.1.1 | Medical condition in easily understood language |
Episodic and Chronic Migraine |
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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 | LLT |
E.1.2 | Classification code | 10066636 |
E.1.2 | Term | Chronic migraine |
E.1.2 | System Organ Class | 100000004852 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027602 |
E.1.2 | Term | Migraine headache |
E.1.2 | System Organ Class | 100000004852 |
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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 the study is to evaluate the long-term safety and tolerability of sc TEV 48125 in the preventive treatment of migraine. |
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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 |
Patients Rolling Over from the Pivotal Efficacy Studies: Patients may be included in this study only if they meet all of the following criteria:
a. Patient signs and dates the informed consent document.
b. Patient must have completed the pivotal efficacy study without major protocol violations.
c. Patients may continue with a stable dose/regimen of the preventive medication they were taking during the pivotal efficacy studies.
d. Patient must be willing and able to comply with study restrictions, to remain at the clinic for the required duration during the study period, and to return to the clinic for the follow-up evaluation as specified in this protocol.
Patients Not Rolling Over from the Pivotal Efficacy Studies: Patients may be included in this study only if they meet all of the following criteria:
a. Males or females aged 18 to 70 years, inclusive, with migraine onset at ≤50 years of age.
b. Patient signs and dates the informed consent document.
c. Patient has history of migraine (according to ICHD-3 criteria [Classification Committee of the IHS, 2013]) or clinical judgment suggests a migraine diagnosis (not better accounted for by another ICHD-3 diagnosis) for ≥12 months prior to screening.
d. Patient fulfills the following criteria for EM or CM with prospectively collected baseline information during the 28-day run-in period:
-Patients with EM:
○ headache occurring on ≥4 and ≤14 days
○ on ≥4 days, fulfilling any of the following:
ICHD-3 diagnostic criteria C and D for 1.1 Migraine without aura
ICHD-3 criteria B and C for 1.2 Migraine with aura
Probable migraine (a migraine subtype where only 1 migraine criterion is missing)
The patient used a triptan or ergot derivative to treat an established headache.
- Patients with CM:
○ headache occurring on ≥15 days
○ on ≥8 days, fulfilling any of the following:
ICHD-3 diagnostic criteria C and D for 1.1 Migraine without aura
ICHD-3 criteria B and C for 1.2 Migraine with aura
Probable migraine (a migraine subtype where only 1 migraine criterion is missing)
The patient used a triptan or ergot derivative to treat an established headache.
e. Not using preventive medications (ie, at least 5 half-lives have passed since last use) or using no more than 1 preventive medication for migraine or other medical conditions (eg, propranolol used for hypertension) if the dose and regimen have been stable for at least 2 months prior to beginning the 28-day run-in period.
f. Body mass index of 17.5 to 37.5 kg/m2 and a total body weight between 45 and 120 kg, inclusive
g. All patients must be of nonchildbearing potential, defined as:
- women surgically sterile by documented complete hysterectomy, bilateral oophorectomy, or bitubal ligations or confirmed to be postmenopausal (at least 1 year since last menses and follicle-stimulating hormone above 35 U/L)
- men surgically sterile by documented vasectomy
or
if of childbearing potential, patients must meet any of the following criteria:
- Patients must simultaneously use 2 forms of highly effective contraception methods with their partners during the entire study period and for 7.5 months after the last dose of study drug.
- Sexual abstinence is only considered a highly effective method if defined as refraining from heterosexual intercourse in the defined period. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the subject. Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods),
declaration of abstinence for the duration of a study, and withdrawal are not acceptable methods of contraception.
h. Female patients of childbearing potential must have a negative serum beta-human chorionic gonadotropin (β-HCG) pregnancy test at screening (confirmed by urine dipstick β-HCG pregnancy test at baseline).
i. The patient demonstrated compliance with the electronic headache diary during the run-in period by entry of headache data on a minimum of 24 out of 28 days (~85% diary compliance).
j. The patient is in good health as determined by a medical and psychiatric history, medical examination, 12-lead ECG, serum chemistry, hematology, coagulation, and urinalysis.
k. The patient must be willing and able to comply with study restrictions, to remain at the clinic for the required duration during the study period, and to return to the clinic for the follow-up evaluation as specified in this protocol.
Patients Rolling Over from the Pivotal Efficacy Studies for ADA Assessment Only: Patients may be included in this study if they sign and date the informed consent document. |
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E.4 | Principal exclusion criteria |
Patients Rolling Over from the Pivotal Efficacy Studies: Patients will be excluded from participating in this study if they meet any of the following criteria:
a. Any finding that, in the judgment of the investigator, is clinically significantly abnormal, including hematology values, serum chemistry, coagulation tests, or urinalysis (abnormal tests may be repeated for confirmation)
b. Pregnant or nursing females
c. Any finding in the baseline 12-lead ECG considered clinically significant in the judgment of the investigator
d. Compliance with daily diary entry lower than 75% at the last month of the double-blind treatment period of the pivotal efficacy study
Patients Not Rolling Over from the Pivotal Efficacy Studies: Patients will be excluded from participating in this study if they meet any of the following criteria:
a. Clinically significant hematological, cardiac, renal, endocrine, pulmonary, gastrointestinal, genitourinary, neurologic, hepatic, or ocular disease, at the discretion of the investigator
b. Evidence or medical history of clinically significant psychiatric issues, including any suicide attempt in the past, or suicidal ideation with a specific plan in the past 2 years
c. History of clinically significant cardiovascular disease or vascular ischemia (such as myocardial, neurological [eg, cerebral ischemia], peripheral extremity ischemia, or other ischemic event) or thromboembolic events (arterial or venous thrombotic or embolic events) such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism
d. Known infection or history of human immunodeficiency virus, tuberculosis, or chronic hepatitis B or C infection
e. Past or current history of cancer in the past 5 years, except for appropriately treated nonmelanoma skin carcinoma
f. Pregnant or nursing females
g. History of hypersensitivity reactions to injected proteins, including monoclonal antibodies
h. Participation in a clinical study of a new chemical entity or a prescription medicine within 2 months before study drug administration or 5 half-lives, whichever is longer
I. Any finding in the baseline 12 lead ECG considered clinically significant in the judgment of the investigator
j. Any finding that, in the judgment of the investigator, is a clinically significant abnormality, including serum chemistry, hematology, coagulation, and urinalysis test values (abnormal tests may be repeated for confirmation)
k. Hepatic enzymes (alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase) >1.5 × the upper limit of the normal range (ULN) after confirmation in a repeat test or suspected hepatocellular damage that fulfills criteria for Hy’s law at screening
l. Serum creatinine >1.5 × the ULN, clinically significant proteinuria, or evidence of renal disease at screening
m. History of alcohol or drug abuse during the past 2 years, or alcohol or drug dependence during the past 5 years
n. The patient cannot participate or successfully complete the study, in the opinion of their healthcare provider or the investigator, for any of the following reasons:
- mentally or legally incapacitated or unable to give consent for any reason
- in custody due to an administrative or a legal decision, under guardianship, or institutionalized
- unable to be contacted in case of emergency
- has any other condition, which, in the opinion of the investigator, makes the patient inappropriate for inclusion in the study
o. Patient is a study center or sponsor employee who is directly involved in the study or the relative of such an employee.
Patients Rolling Over from the Pivotal Efficacy Studies for ADA Assessment Only: Not applicable. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• occurrence of adverse events throughout the study
• changes from baseline in clinical laboratory (serum chemistry, hematology, coagulation, and urinalysis) test results
• abnormal standard 12-lead electrocardiogram (ECG) findings
• changes from baseline in vital signs (pulse, systolic and diastolic blood pressure, body temperature, and respiratory rate) measurements
• abnormal physical examination findings
• abnormal local injection site tolerability findings (ie, erythema, induration, and ecchymosis) and occurrence of injection site pain
• suicidal ideation and behavior as suggested by the electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) |
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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) |
There are no secondary efficacy endpoints |
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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 | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
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) | 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 | No |
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.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 23 |
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 |
Canada |
Czech Republic |
Germany |
Israel |
Japan |
Poland |
Russian Federation |
Spain |
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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The end of the study is defined as the date the last patient attends the follow-up visit |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |