A Study to Evaluate the Efficacy and Safety of Fremanezumab for Preventive Treatment of Migraine in Patients With Major Depressive Disorder
Condition: Migraine; Major Depressive Disorder
MeSH terms: Migraine Disorders; Depressive Disorder; Depression; Depressive Disorder, Major
Intervention: Fremanezumab; Placebo
Intervention description: Monthly 225 mg subcutaneous; Matching Placebo
Phase: Phase 4
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 353.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      The primary objective is to evaluate the efficacy of monthly 225 mg sc fremanezumab in adult
      participants with migraine and major depressive disorder (MDD)

      The secondary objectives are to evaluate the efficacy of monthly 225 mg sc of fremanezumab in
      adult participants with migraine and MDD on the reduction of MDD symptoms, responder rates in
      monthly migraine days, improving quality of life, improving disability, and the safety and
      tolerability of monthly 225 mg sc and quarterly 675 mg sc fremanezumab in adult participants
      with migraine and MDD.

      The total duration of participant participation in the study is planned to be approximately
      28 weeks.
    

Eligibility criteria:

        Inclusion Criteria:

          -  The participant has a diagnosis of migraine with onset at ≤50 years of age.

          -  Prior to the screening visit 1 the participant has a 12-month history of either
             migraine or headache consistent with migraine

          -  The participant agrees not to initiate any migraine preventive during the study. Up to
             30% of participants, however, may take a single such medication previously prescribed
             for the treatment of migraine.

          -  The participant has a history of major depressive disorder (MDD) at least 12 months
             prior to the screening visit. Participants may take a single medication prescribed for
             the treatment of depression as long as the dose of that medication has been stable for
             at least 8 weeks prior to the screening visit and expects to remain at the stable dose
             throughout the study.

          -  The participant has a body weight ≥ 45 kg and a body mass index within the range of
             17.5 to 34.9 kg/m2, inclusive.

          -  Women of child-bearing potential whose male partners are potentially fertile (ie, no
             vasectomy) must use highly effective birth control methods for the duration of the
             study and for 6 months after discontinuation of IMP.

          -  Men must be sterile or, if they are potentially fertile/reproductively competent (not
             congenitally sterile) and their female partners are of child-bearing potential, must
             use a condom for the duration of the study and for 6 months after discontinuation of
             IMP.

        NOTE: Additional criteria apply, please contact the investigator for more information

        Exclusion Criteria:

          -  The participant has failed 4 or more different medication classes to treat depression
             in their lifetime.

          -  The participant has used an intervention/device (eg, scheduled nerve blocks,
             implantable vagal nerve stimulation, and transcranial magnetic stimulation) for
             migraine or depression during the 2 months prior to screening.

          -  The participant has used electroconvulsive therapy at any time.

          -  The participant suffers from constant or nearly constant headache, defined as having
             headaches for more than 80% of the time he/she is awake, and less than 4 days without
             headache per month. Daily headache is acceptable if participant has headaches 80% or
             less of the time he/she is awake on most days.

          -  The participant has a clinical history of a severe or uncontrolled psychiatric
             disorder, to include the following, or at the discretion of the investigator for any
             clinically significant psychiatric history that would likely interfere with full
             participation in the study:

               -  Lifetime exclusion: suicide attempt

               -  In the past 6 months exclusion: suicidal ideation, or other psychoactive spectrum
                  disorders including schizoaffective disorder, delusional disorder, depression
                  with psychotic features, and catatonic disorder.

          -  The participant has a known infection or history of human immunodeficiency virus,
             tuberculosis, any history of Lyme disease, or chronic hepatitis B or C infection.

          -  The participant has a past or current history of cancer, except for appropriately
             treated non-melanoma skin carcinoma.

          -  The participant is a pregnant or nursing female or plans to become pregnant during the
             study, including the 6-month period after the administration of the last dose.

          -  The participant has a history of hypersensitivity reactions to injected proteins,
             including monoclonal antibodies, or a history of Stevens-Johnson Syndrome or toxic
             epidermal necrolysis syndrome.

          -  Participant has received onabotulinumtoxinA for migraine or for any medical or
             cosmetic reasons requiring injections in the head, face, or neck during the 3 months
             before screening visit.

          -  The participant has a history of hypersensitivity reactions to injected proteins,
             including monoclonal antibodies.

          -  The participant has participated in a clinical study of a new chemical entity or a
             prescription medicine within 2 months of the screening visit or 3 months in case of
             biologics if the half-life of the biologics is unknown or 5 half-lives, whichever is
             longer, or is currently participating in another study of an IMP (or a medical
             device).

          -  The participant has failed treatment (based on tolerability and/or a lack of efficacy)
             with any monoclonal antibodies targeting the CGRP pathway (erenumab, eptinezumab,
             galcanezumab, or fremanezumab) or have taken the medications within 5 half-lives of
             the screening visit (V1) or take them during the study.

          -  The participant has any clinically significant uncontrolled medical condition (treated
             or untreated).

          -  The participant has a history of alcohol or drug abuse in the opinion of the
             investigator.

          -  The participant has evidence or medical history of psychotic symptoms as per the
             Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria
             such as delusions, hallucinations, or disorganized speech in the past 1 month.

        NOTE: Additional criteria apply, please contact the investigator for more information