Efficacy and Safety of Subcutaneous Administration of Fremanezumab (TEV-48125) for the Preventive Treatment of Migraine (HALO)

Teva Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: Migraine

Treatments: Drug: Fremanezumab; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02638103

TV48125-CNS-30051

2015-004550-18 (EudraCT Number)

Details and patient eligibility

About

A study to evaluate the long-term safety, tolerability, and efficacy of subcutaneous (SC) administration of TEV-48125 in adult participants with chronic migraine (CM) or episodic migraine (EM). Participants with CM or EM who complete the pivotal efficacy studies of TEV-48125 (TV48125-CNS-30049 [NCT02621931] and TV48125-CNS-30050 [NCT02629861]) and agree to participate in this study; and new participants meeting eligibility criteria (not rolling over from pivotal studies), will be enrolled in this study.

Enrollment: 1,890 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Participants Rolling Over from the Pivotal Efficacy Studies:

• Participant must have signed and dated the informed consent document.

• Participant must have completed the pivotal efficacy study without major protocol violations.

  • Additional criteria apply, please contact the investigator for more information.

Participants Not Rolling Over from the Pivotal Efficacy Studies:

• Males or females aged 18 to 70 years, inclusive, with migraine onset at less than or equal to (≤) 50 years of age.

• Participant signed and dated the informed consent document.

• Participant has a history of migraine or clinical judgment suggests a migraine diagnosis.

• Participant fulfills the criteria for EM or CM with prospectively collected baseline information during the 28-day run-in period.

• Body mass index (BMI) of 17.5 to 37.5 kilograms/square meter (kg/m^2) and a total body weight between 45 and 120 kg, inclusive.

• All participants must be of non-childbearing potential.

  1. Participants must simultaneously use 2 forms of highly effective contraception methods.
  2. Participants will remain abstinent throughout the study.

• Female participants of childbearing potential must have a negative serum beta-human chorionic gonadotropin (β-HCG) pregnancy test prior at screening (confirmed by urine dipstick β-HCG pregnancy test at baseline).

• The participant 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.

  • Additional criteria apply, please contact the investigator for more information

Exclusion criteria

Participants Rolling Over from the Pivotal Efficacy Studies:

• Pregnant or nursing females

• Compliance with daily diary entry lower than 75 percent (%) at the last month of the double-blind treatment period of the pivotal efficacy study.

  • Additional criteria apply, please contact the investigator for more information.

Participants Not Rolling Over from the Pivotal Efficacy Studies:

• Clinically significant findings at the discretion of the investigator.

• 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.

• History of clinically significant cardiovascular disease or vascular ischemia (such as myocardial, neurological [for example; 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 -Known infection or history of human immunodeficiency virus, tuberculosis, or chronic hepatitis B or C infection.

• Past or current history of cancer in the past 5 years, except for appropriately treated nonmelanoma skin carcinoma.

• Pregnant or nursing females.

• History of hypersensitivity reactions to injected proteins, including monoclonal antibodies.

• 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.

• History of alcohol or drug abuse during the past 2 years, or alcohol or drug dependence during the past 5 years.

• The participant cannot participate or successfully complete the study, in the opinion of their healthcare provider or the investigator, for any of the following reasons:

  1. mentally or legally incapacitated or unable to give consent for any reason.
  2. in custody due to an administrative or a legal decision, under guardianship, or institutionalized.
  3. unable to be contacted in case of emergency.
  4. has any other condition, which, in the opinion of the investigator, makes the participant inappropriate for inclusion in the study.

• Participant is a study center or sponsor employee who is directly involved in the study or the relative of such an employee.

  • Additional criteria apply, please contact the investigator for more information.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,890 participants in 4 patient groups

TEV-48125 225 mg Monthly: New/Placebo Rollover Participants

Experimental group

Description:

Participants with CM who were randomized to the placebo treatment group or participants who do not rollover from the pivotal efficacy study, will receive fremanezumab 675 milligrams (mg) SC as loading dose (3 injections of fremanezumab 225 mg/1.5 milliliters \[mL\] on Day 0) followed by 11 monthly SC doses of fremanezumab at 225 mg (1 injection of fremanezumab 225 mg/1.5 mL and 2 injections of placebo 1.5 mL on Days 84, 168, and 252; and 1 injection of fremanezumab 225 mg/1.5mL on Days 28, 56, 112, 140, 196, 224, 280, and 308). Participants with EM who were randomized to the placebo treatment group or participants who do not rollover from the pivotal efficacy study, will receive 12 monthly SC doses of fremanezumab at 225 mg (1 injection of fremanezumab 225 mg/1.5 mL and 2 injections of placebo 1.5 mL on Days 0, 84, 168, and 252; and 1 injection of fremanezumab 225 mg/1.5 mL on Days 28, 56, 112, 140, 196, 224, 280, and 308).

Treatment:

Drug: Placebo

Drug: Fremanezumab

TEV-48125 225 mg Monthly: Active Rollover Participants

Experimental group

Description:

Participants with CM who were randomized to the active treatment group (Fremanezumab 675/225 mg) in the pivotal efficacy study, will receive fremanezumab 675 mg SC as loading dose (3 injections of fremanezumab 225 mg/1.5 mL on Day 0) followed by 11 monthly SC doses of fremanezumab at 225 mg (1 injection of fremanezumab 225 mg/1.5mL and 2 injections of placebo 1.5 mL on Days 84, 168, and 252; and 1 injection of fremanezumab 225 mg/1.5mL on Days 28, 56, 112, 140, 196, 224, 280, and 308). Participants with EM who were randomized to the active treatment group (Fremanezumab 225 mg) in the pivotal efficacy study, will receive 12 monthly SC doses of fremanezumab at 225 mg (1 injection of fremanezumab 225 mg/1.5 mL and 2 injections of placebo 1.5 mL on Days 0, 84, 168, and 252; and 1 injection of fremanezumab 225 mg/1.5 mL on Days 28, 56, 112, 140, 196, 224, 280, and 308).

Treatment:

Drug: Placebo

Drug: Fremanezumab

TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants

Experimental group

Description:

Participants with CM or EM who were randomized to the placebo treatment group or participants who do not rollover from the pivotal efficacy study, will receive fremanezumab 675 mg SC once every 3 months for 12 months for a total of 4 doses (3 injections of fremanezumab 225 mg/1.5 mL on Days 0, 84, 168, and 252; and 1 injection of placebo 1.5 mL on Days 28, 56, 112, 140, 196, 224, 280, and 308).

Treatment:

Drug: Placebo

Drug: Fremanezumab

TEV-48125 675 mg Quarterly: Active Rollover Participants

Experimental group

Description:

Participants with CM or EM who were randomized to the active treatment group (Fremanezumab 675 mg) in the pivotal efficacy study, will receive fremanezumab 675 mg SC once every 3 months for 12 months for a total of 4 doses (3 injections of fremanezumab 225 mg/1.5 mL on Days 0, 84, 168, and 252; and 1 injection of placebo 1.5 mL on Days 28, 56, 112, 140, 196, 224, 280, and 308).

Treatment:

Drug: Placebo

Drug: Fremanezumab