• change from baseline in the individual components of the Fibromyalgia Impact Questionnaire Revised (FIQR): symptom subscore, impact subscore, and functional subscore score [ Time Frame: Baseline up to week 16 ]
  The FIQR is a commonly used instrument in the evaluation of FM patients. It contains 21 questions in 3 domains: function (9 questions), overall impact (2 questions), and symptoms (10 questions). Questions are graded on a 0 to 10 numeric scale with 10 being the worst.
• responder rate of the Patient Global Impression of Change (PGIC) rating (percentage of patients much improved or very much improved) [ Time Frame: Baseline up to week 16 ]
  Scale evaluates all aspects of patients' health and assesses if there has been an improvement or decline in clinical status since the start of the study. Improvement is recorded on a 7-point scale, with 1 indicating very much improved and 7 indicating very much worse.
• percentage of patients who experience a ≥30% reduction in the weekly average of the daily average PI-NRS score [ Time Frame: Baseline up to week 16 ]
  An 11-point pain intensity numerical rating scale where 0=no pain and 10=worst possible pain.
• percentage of patients who experience a ≥50% reduction in the weekly average of the daily average PI-NRS score [ Time Frame: Baseline up to week 16 ]
  An 11-point pain intensity numerical rating scale where 0=no pain and 10=worst possible pain.
• change from baseline in the weekly average of the daily worst PI-NRS score over the past 24 hours [ Time Frame: Baseline up to week 16 ]
  An 11-point pain intensity numerical rating scale where 0=no pain and 10=worst possible pain.
• change from baseline in the Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance Short Form (SF) 8a score [ Time Frame: Baseline up to week 16 ]
  Contains 8 items with a score range from 8 to 40. Each question has 5 response options ranging in value from 1 to 5 over the past 7 days. To find the total raw score for an SF with all questions answered, sum the values of the response to each question. For the adult 8-item form, the lowest possible raw score is 8; the highest possible raw score is 40, indicating worst sleep.
• change from baseline in the PROMIS Physical Function SF12a score [ Time Frame: Baseline up to week 16 ]
  Contains 12 items with a score ranging from 12 to 36. The PROMIS Physical Function Scale measures self-reported capability rather than actual performance of physical activities. This includes the functioning of one's upper extremities (dexterity), lower extremities (walking or mobility), and central regions (neck, back), as well as instrumental activities of daily living, such as running errands over the past over the past 7 days. A single Physical Function capability score is obtained from a SF. A lower score indicates more limited physical disability.
• change from baseline in the PROMIS Fatigue SF8a score [ Time Frame: Baseline up to week 16 ]
  Contains 8 items with a score range from 8 to 40. Each question has 5 response options ranging in value from 1 to 5 over the past 7 days. To find the total raw score for an SF with all questions answered, sum the values of the response to each question. For the adult 8-item form, the lowest possible raw score is 8; the highest possible raw score is 40, indicating worst sleep.
• number of adverse events [ Time Frame: Screening up to week 16 ]
• change from randomization in the clinical laboratory test: serum chemistry [ Time Frame: Baseline up to week 16 ]
• change from randomization in the clinical laboratory test: hematology [ Time Frame: Baseline up to week 16 ]
• change from randomization in the clinical laboratory test: urinalysis [ Time Frame: Baseline up to week 16 ]
• change from baseline in vital signs: pulse [ Time Frame: Baseline up to week 16 ]
• change from baseline in vital signs: respiratory rate [ Time Frame: Baseline up to week 16 ]
• change from baseline in vital signs: systolic blood pressure [ Time Frame: Baseline up to week 16 ]
• change from baseline in vital signs: diastolic blood pressure [ Time Frame: Baseline up to week 16 ]
• change from baseline in vital signs: oral body temperature [ Time Frame: Baseline up to week 16 ]
• clinically significant changes in physical examination including body weight [ Time Frame: Baseline up to week 16 ]
• abnormal standard 12-lead electrocardiogram (ECG) findings [ Time Frame: Baseline up to week 16 ]
• tolerability at the injection site [ Time Frame: Baseline up to week 16 ]
  including but not limited to pain, erythema, induration, and ecchymosis
• occurrence of hypersensitivity/anaphylaxis reactions using standardized criteria [ Time Frame: Baseline up to week 16 ]
  See APPENDIX C. CLINICAL CRITERIA FOR DIAGNOSING ANAPHYLAXIS
• suicidal ideation and behavior [ Time Frame: Baseline up to week 16 ]
  as measured by the Columbia-Suicide Severity Rating Scale (C-SSRS). The C-SSRS is an assessment tool that evaluates suicidal ideation and behavior. Scale range: Yes or No response to 10 questions, with minimum to maximum range of 0 to 10. Lower score represents better outcomes.
• number (%) of patients who did not complete the study (Kaplan-Meier Survival Analysis) due to adverse events [ Time Frame: Baseline up to week 16 ]
• number (%) of patients who did not complete the study (Kaplan-Meier Survival Analysis) due to lack of efficacy [ Time Frame: Baseline up to week 16 ]

• change from baseline in the individual components of the Fibromyalgia Impact Questionnaire Revised (FIQR): symptom subscore, impact subscore, and functional subscore score [ Time Frame: Baseline up to week 16 ]
• responder rate of the Patient Global Impression of Change (PGIC) rating (percentage of patients much improved or very much improved) [ Time Frame: Baseline up to week 16 ]
• percentage of patients who experience a ≥30% reduction in the weekly average of the daily average PI-NRS score [ Time Frame: Baseline up to week 16 ]
• percentage of patients who experience a ≥50% reduction in the weekly average of the daily average PI-NRS score [ Time Frame: Baseline up to week 16 ]
• change from baseline in the weekly average of the daily worst PI-NRS score over the past 24 hours [ Time Frame: Baseline up to week 16 ]
• change from baseline in the Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance Short Form (SF) 8a score [ Time Frame: Baseline up to week 16 ]
• change from baseline in the PROMIS Physical Function SF12a score [ Time Frame: Baseline up to week 16 ]
• change from baseline in the PROMIS Fatigue SF8a score [ Time Frame: Baseline up to week 16 ]
• number of adverse events [ Time Frame: Baseline up to week 16 ]
• change from randomization in the clinical laboratory test: serum chemistry [ Time Frame: Baseline up to week 16 ]
• change from randomization in the clinical laboratory test: hematology [ Time Frame: Baseline up to week 16 ]
• change from randomization in the clinical laboratory test: urinalysis [ Time Frame: Baseline up to week 16 ]
• change from baseline in vital signs: pulse [ Time Frame: Baseline up to week 16 ]
• change from baseline in vital signs: respiratory rate [ Time Frame: Baseline up to week 16 ]
• change from baseline in vital signs: systolic blood pressure [ Time Frame: Baseline up to week 16 ]
• change from baseline in vital signs: diastolic blood pressure [ Time Frame: Baseline up to week 16 ]
• change from baseline in vital signs: oral body temperature [ Time Frame: Baseline up to week 16 ]
• clinically significant changes in physical examination including body weight [ Time Frame: Baseline up to week 16 ]
• abnormal standard 12-lead electrocardiogram (ECG) findings [ Time Frame: Baseline up to week 16 ]
• tolerability at the injection site [ Time Frame: Baseline up to week 16 ]
  including but not limited to pain, erythema, induration, and ecchymosis
• occurrence of hypersensitivity/anaphylaxis reactions using standardized criteria [ Time Frame: Baseline up to week 16 ]
  See APPENDIX C. CLINICAL CRITERIA FOR DIAGNOSING ANAPHYLAXIS
• suicidal ideation and behavior [ Time Frame: Baseline up to week 16 ]
  as measured by the Columbia-Suicide Severity Rating Scale (C-SSRS)
• number (%) of patients who did not complete the study (Kaplan-Meier Survival Analysis) due to adverse events [ Time Frame: Baseline up to week 16 ]

The primary objective of the study is to estimate the treatment effect of fremanezumab administered subcutaneously in reducing pain in adult patients with FM. A secondary objective is to evaluate the effect of fremanezumab on other efficacy measures, including pain, quality of life, sleep, fatigue, improvement in health, physical functioning, and mood. Another secondary objective is to evaluate the safety and tolerability of fremanezumab administered subcutaneously in adult patients with FM.

The total duration of patient participation in the study is planned to be 21 weeks, consisting of a screening period of up to 5 weeks (ranging from 17 to 35 days), and a double-blind treatment period of 16 weeks.

• Drug: Fremanezumab - Dose A
  Administered subcutaneously (sc) for 4 monthly doses at Visits 3, 4, 5, and 6.
• Drug: Fremanezumab - Dose B
  Administered subcutaneously (sc) for 4 monthly doses at Visits 3, 4, 5, and 6.
• Drug: Placebo
  Administered subcutaneously (sc) for 4 monthly doses at Visits 3, 4, 5, and 6.

• Experimental: Fremanezumab - Dose A
  Intervention: Drug: Fremanezumab - Dose A
• Experimental: Fremanezumab - Dose B
  Intervention: Drug: Fremanezumab - Dose B
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

Inclusion Criteria:

• approved for study participation by the Fibromyalgia Eligibility Review Committee
• body mass index of 18.5 to 45 kg/m2 and a body weight ≥45 kg
• agree to use only acetaminophen as rescue medication for FM-related pain (up to 1000 mg per dose and not to exceed 3000 mg/day for any indication throughout the study period)
• non-pharmacologic interventions (including normal daily exercise routines, chiropractic care, physical therapy, psychotherapy, and massage therapy) are unchanged for a minimum of 30 days prior to screening and will remain unchanged throughout the study
• agree to maintain a usual and unchanged physical exercise regimen

• must be of nonchildbearing potential or , 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 menstrual period) and
  • menopausal women confirmed by a follicle-stimulating hormone >35 U/L
  • men surgically sterile by documented vasectomy OR

If of childbearing potential, patients must meet any of the following criteria:

• must use highly effective contraception method (Appendix G) with their partners during the entire study period and for 5 months after the last dose of the IMP.
• sexual abstinence is only considered a highly effective method if defined as refraining from heterosexual intercourse in the defined period.

• 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).

  • must agree not to participate in another interventional study from the screening period through the EOS Visit o Additional criteria apply, please contact the investigator for more information

Exclusion Criteria:

• unable or unwilling to discontinue/washout of prohibited medications
• ongoing pain that would confound or interfere with the assessment of the patient's FM pain or require excluded therapies during the patient's participation in this study.
• surgery planned during the study period
• receiving prophylactic treatment for migraine-related disorders, including topiramate, valproic acid, onabotulinumtoxinA, amitriptyline, and nortriptyline
• known history of clinically significant or unstable hematologic, cardiac, or thromboembolic events
• known history of suicide attempt, suicidal behavior, or suicidal ideation within the last 12 months
• lifetime history of any psychotic and/or bipolar disorder
• current, untreated, moderate or severe major depressive disorder and/or anxiety
• known history of hypersensitivity reactions to injected proteins, including mAbs and animal venoms, or a history of Stevens-Johnson Syndrome/toxic epidermal necrolysis syndrome o Additional criteria apply, please contact the investigator for more information