A Study to Test the Effectiveness and Safety of Fremanezumab on Participants With Fibromyalgia

Study Overview
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Brief Summary
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The primary objective of the study is to estimate the treatment effect of fremanezumab administered subcutaneously (SC) in reducing pain in adult participants with fibromyalgia (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 SC in adult participants with FM. The total duration of participant 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.

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Proof of Concept Study of the Efficacy and Safety of Fremanezumab for Treatment of Patients With Fibromyalgia

Conditions
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Fibromyalgia

Intervention / Treatment
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* Drug: Fremanezumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: approved for study participation by the Fibromyalgia Eligibility Review Committee body mass index of 18.5 to 45 kilograms (kg)/square meter (m^2) 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 units (U)/liter (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 with their partners during the entire study period and for 5 months after the last dose of the study drug. sexual abstinence is only considered a highly effective method if defined as refraining from heterosexual intercourse in the defined period. female participants 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 end of study (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 participant's FM pain or require excluded therapies during the participant'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 monoclonal antibodies (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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants will receive placebo matching to fremanezumab SC on Days 1, 29, 57, and 85. | Drug: Placebo<br>* Placebo matching to fremanezumab will be administered per schedule specified in the arm description.<br>|
| Experimental: Fremanezumab Dose A<br>Participants will receive fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85. | Drug: Fremanezumab<br>* Fremanezumab will be administered per dose and schedule specified in the arm description.<br>|
| Experimental: Fremanezumab Dose B<br>Participants will receive fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85. | Drug: Fremanezumab<br>* Fremanezumab will be administered per dose and schedule specified in the arm description.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Weekly Average of the Daily Average Pain Intensity-Numerical Rating Scale (PI-NRS) Score Over the Past 24 Hours at Week 12 | The PI-NRS is an 11-point pain intensity numerical rating scale where 0=no pain and 10=worst possible pain; higher scores indicating more pain. Weekly average of the daily average PI-NRS pain score over the past 24 hours was derived using formula: Summation of non-missing efficacy variable in an analysis week divided by the number of days with non-missing efficacy variable in the analysis week. Baseline was defined as the last 14 days before the first dose of study drug. | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Individual Components of the Fibromyalgia Impact Questionnaire Revised (FIQR) Score: Symptom Subscore, Impact Subscore, and Functional Subscore at Week 12 | The FIQR is a commonly used instrument in the evaluation of fibromyalgia participants. 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. All questions are framed in the context of the last 7 days. The sub-total score for each domain is the summation of scores in the domain. The function sub-total score ranges from 0 (better) to 90 (worst), with a lower score indicating better (higher) function; overall impact sub-total score ranges from 0 to 20, with a lower score indicating better (lower) impact; the symptoms sub-total score ranges from 0 to 100, with a lower score indicating a better (lower) level of symptoms. Baseline was defined as the last 14 days before the first dose of study drug. | Baseline, Week 12 | 
| Responder Rate of the Patient Global Impression of Change (PGIC) Rating: Number of Participants Who Were Much Improved or Very Much Improved at Week 12 | The PGIC scale evaluates all aspects of participants' health and assesses if there has been an improvement or decline in clinical status since the start of the study. Participants recorded responses to the PGIC scale at Week 12. Improvement was recorded on a 7-point scale, with 1 = very much improved, 2 = Much Improved, 3 = Minimally Improved, 4 = No Change, 5 = Minimally Worse, 6 = Much Worse, and 7 = Very Much Worse. Scale much improved or very much improved were considered improved. | Week 12 | 
| Number of Participants Who Experienced ≥30% Reduction From Baseline in Weekly Average of Daily Average PI-NRS Score at Week 12 | The PI-NRS is an 11-point pain intensity numerical rating scale where 0=no pain and 10=worst possible pain; higher scores indication more pain. Weekly average of the daily average PI-NRS pain score over the past 24 hours was derived using formula: Summation of non-missing efficacy variable in an analysis week divided by the number of days with non-missing efficacy variable in the analysis week. | Week 12 | 
| Number of Participants Who Experienced ≥50% Reduction From Baseline in Weekly Average of Daily Average PI-NRS Score at Week 12 | The PI-NRS is an 11-point pain intensity numerical rating scale where 0=no pain and 10=worst possible pain; higher scores indication more pain. Weekly average of the daily average PI-NRS pain score over the past 24 hours was derived using formula: Summation of non-missing efficacy variable in an analysis week divided by the number of days with non-missing efficacy variable in the analysis week. | Week 12 | 
| Change From Baseline in the Weekly Average of Daily Worst PI-NRS Score Over Past 24 Hours at Week 12 | The PI-NRS is an 11-point pain intensity numerical rating scale where 0=no pain and 10=worst possible pain; higher scores indication more pain. Weekly average of the daily worst PI-NRS pain score over the past 24 hours was derived using formula: Summation of non-missing efficacy variable in an analysis week divided by the number of days with non-missing efficacy variable in the analysis week. Baseline was defined as the last 14 days before the first dose of study drug. | Baseline, Week 12 | 
| Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance Short Form (SF) 8a T-score at Week 12 | The PROMIS SF8a scale contains 8 items and assesses sleep disturbance over the past 7 days. One item assessing overall sleep quality use a scale of very poor, poor, fair, good, or very good. Other 7 items use a scale of not at all, a little bit, somewhat, quite a bit, or very much. Each item of the PROMIS sleep disturbance SF8a is on 5-point scales (1 to 5), with 1 for the lowest sleep disturbance and 5 for the highest sleep disturbance. The total score ranging from 8 (lowest sleep disturbance) to 40 (highest sleep disturbance) was calculated as the summation of 8 non-missing scores. T-score was calculated from the total raw score using the scoring table (PROMIS-Sleep Disturbance Scoring Manual) with a mean of 50 and a standard deviation of 10. Possible range for T-score is 30 to 80, with higher scores indicating greater severity of sleep impairment. | Baseline, Week 12 | 
| Change From Baseline in the PROMIS Physical Function SF 12a Scale Score at Week 12 | The PROMIS physical function scale measures self-reported capability. 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 7 days. A single physical function capability score is obtained from a SF. The PROMIS physical function SF12a scale contains 12 items with 5-point scales (1 [not at all] to 5 [very much]) for each item with a total score ranging from 12 (poor physical function) to 60 (better physical function). A higher score indicates greater level of physical capability. Total raw score was calculated as the summation of 12 non-missing scores for participants who can walk 25 feet or summation of 6 non-missing scores for participants who cannot walk for 25 feet. The calculated total raw score was converted into scale score using the scoring tables (PROMIS-Physical Function Scoring Manual). | Baseline, Week 12 | 
| Change From Baseline in the PROMIS Fatigue SF 8a T-Score at Week 12 | The PROMIS Fatigue SF8a contains 8 items with 5-point scales (1 [never] to 5 [always]) for each item over the past 7 days. The total raw score ranges from 8 (lowest level of fatigue) to 40 (highest level of fatigue) was calculated as the summation of 8 non-missing scores. T-score was calculated from the total raw score using the scoring table (PROMIS-Fatigue Scoring Manual) with a mean of 50 and a standard deviation of 10; scores higher than 50 indicate greater fatigue compared to the reference population. | Baseline, Week 12 | 
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse events (SAEs) were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. Any AE occurring on or after the first dose of study drug is considered a treatment-emergent AE (TEAE). A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. | Baseline up to Week 16 | 
| Number of Participants With at Least 1 Potentially Clinically Significant Abnormal Serum Chemistry Value | Potentially clinically significant serum chemistry abnormalities included: Blood urea nitrogen ≥10.71 millimoles (mmol)/liter (L) and Gamma-glutamyl transpeptidase (GGT) ≥3 * upper limit of normal (ULN). | Baseline up to Week 16 | 
| Number of Participants With at Least 1 Potentially Clinically Significant Abnormal Hematology Value | Potentially clinically significant hematological abnormalities included: White blood cells (WBCs) count ≤3.0 * 10^9/L; Hemoglobin ≤95 grams (g)/L in females; Hematocrit <0.32 L/L in females; Platelets ≥700 * 10^9/L; and Eosinophils/Leukocytes ≥10%. | Baseline up to Week 16 | 
| Number of Participants With at Least 1 Potentially Clinically Significant Urinalysis Abnormalities |  | Baseline up to Week 16 | 
| Number of Participants With at Least 1 Clinically Significant Abnormal Vital Signs Value | Clinically significant vital signs abnormalities included: Systolic blood pressure (BP): ≤90 millimeters of mercury (mmHg) and decrease from baseline of 20 mm Hg; Diastolic BP: ≥105 mmHg and increase from baseline of ≥15 mmHg or ≤50 mmHg and decrease from baseline of ≥15 mmHg. | Baseline up to Week 16 | 
| Number of Participants With at Least 1 Physical Examination Abnormal Finding | Physical examination included: General appearance, HEENT (head, ears, eyes, nose, and throat examination), chest and lungs, heart, cardiovascular, abdomen, musculoskeletal, skin, lymph nodes, neurological, and extremities/back. | Baseline up to Week 16 | 
| Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | The number of participants with a difference (shift) from baseline in any of the following ECG parameters is reported by group: heart rate, PR interval, QRS interval, RR interval, QT interval corrected usingthe Fridericia formula (QTcF) and QT interval corrected using the Bazett's formula (QTcB). Shifts represented as Baseline - endpoint value (last observed post-baseline value). | Baseline to Week 16 | 
| Number of Participants With at Least 1 Injection Site AE | Injection site AEs included injection site pain, injection site erythema, injection site induration, injection site pruritus, injection site bruising, injection site nodule, injection site swelling, and injection site warmth. | Baseline up to Week 16 | 
| Number of Participants With Hypersensitivity/Anaphylaxis Reactions |  | Baseline up to Week 16 | 
| Time to Withdrawal of Treatment Due to Lack of Efficacy |  | Baseline up to Week 16 | 
| Time to Withdrawal of Treatment Due to AEs |  | Baseline up to Week 16 |