Episodic Cluster Headache
Conditions
Brief summary
This is a 13-week, multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel-group study to compare the efficacy and safety of 2 dose regimens of TEV-48125 (Fremanezumab) versus placebo in adult participants for the prevention of ECH.
Interventions
DRUGFremanezumab
Fremanezumab will be administered per dose and schedule specified in the arm.
DRUGPlacebo
Placebo matching to fremanezumab will be administered per schedule specified in the arm.
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* The participant has a history of ECH according to the International Classification of Headache Disorders - 3 beta criteria (Headache Classification Committee of the International Headache Society \[IHS\] 2013) for ≥12 months prior to screening. * The participant has a total body weight of ≥45 kg (99 lbs.) * The participant is in good health in the opinion of the investigator * Women of childbearing potential (WOCBP) whose male partners are potentially fertile (that is, no vasectomy) must use highly effective birth control methods for the duration of the study. * Men must be sterile, or if they are potentially fertile/reproductively competent (not surgically \[for example, vasectomy\] or congenitally sterile) and their female partners are of childbearing potential, must agree to use, together with their female partners, acceptable birth control for the duration of the study. * If a participant is receiving Botox, it should be in a stable dose regimen, considered as having ≥2 cycles of Botox prior to screening. The participant should not receive Botox during the run-in period up to the evaluation period (4 weeks) where the primary endpoint is evaluated. * Additional criteria apply, please contact the investigator for more information
Exclusion criteria
* The participant has used systemic steroids for any medical reason (including treatment of the current CH cycle within ≤7 days prior to screening The participant has used an intervention/device (for example, scheduled nerve blocks) for headache during the 4 weeks prior to screening. * The participant has clinically significant hematological, renal, endocrine, immunologic, pulmonary, gastrointestinal, genitourinary, cardiovascular, neurologic, hepatic, or ocular disease at the discretion of the investigator. * The participant has evidence or medical history of clinically significant psychiatric issues determined at the discretion of the investigator. * The participant has a past or current history of cancer or malignant tumor in the past 5 years, except for appropriately treated non-melanoma skin carcinoma. * The participant is pregnant or lactating. * The participant has a history of hypersensitivity reactions to injected proteins, including monoclonal antibodies. * The participant has participated in a clinical study of a monoclonal antibody within 3 months or 5 half-lives before administration of the first dose of the IMP, whichever is longer, unless it is known that the participant received placebo during the study. * The participant has a history of prior exposure to a monoclonal antibody targeting the calcitonin gene-related peptide (CGRP) pathway (AMG 334, ALD304, LY2951742, or fremanezumab). If participant has participated in a clinical study with any of these monoclonal antibodies, it has to be confirmed that the participant received placebo in order to be eligible for this study. * The participant is an employee of the sponsor/participating study center who is directly involved in the study or is the relative of such an employee. * The participant has an active implant for neurostimulation used in the treatment of CH. * The participant is a member of a vulnerable population (for example, people kept in detention). * The participant has a history of alcohol abuse prior to screening and/or drug abuse that in the investigator's opinion could interfere with the study evaluations or the participant's safety . * Additional criteria apply, please contact the investigator for more information
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in the Weekly Average Number of Cluster Headache (CH) Attacks During the 4-Week Period After Administration of the First Dose of the IMP | Baseline (Week 0), up to Week 4 | A CH attack was defined as a severe or very severe unilateral orbital, supraorbital, and/or temporal pain lasting 15 to 180 minutes with either or both of the following 2 categories: 1) at least 1 of the following symptoms or signs, ipsilateral to the headache: -conjunctival injection and/or lacrimation; -nasal congestion and/or rhinorrhea; -eyelid edema; -forehead and facial sweating; -forehead and facial flushing; -sensation of fullness in the ear; -miosis and/or ptosis. 2) a sense of restlessness or agitation. Least Squares (LS) mean calculated using analysis of covariance (ANCOVA) model with baseline preventive medication use (yes or no), sex, region (United States \[US\]/Canada or other), and treatment as fixed effects and the baseline number of CH attacks as a covariate. Change from baseline in the overall weekly average number of CH attacks during the 4-week period after administration of the first dose of study drug (based on Week 0 to 4 data) is reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Weekly Average Number of CH Attacks During the 12-Week Period After Administration of the First Dose of the IMP | Baseline (Week 0), up to Week 12 | A CH attack was defined as a severe or very severe unilateral orbital, supraorbital, and/or temporal pain lasting 15 to 180 minutes with either or both of the following 2 categories: 1) at least 1 of the following symptoms or signs, ipsilateral to the headache: -conjunctival injection and/or lacrimation; -nasal congestion and/or rhinorrhea; -eyelid edema; -forehead and facial sweating; -forehead and facial flushing; -sensation of fullness in the ear; -miosis and/or ptosis. 2) a sense of restlessness or agitation. LS mean calculated using mixed model for repeated measures (MMRM) with baseline preventive medication use (yes or no), gender, region (US/Canada or other), treatment, month, and month-by-treatment interaction as fixed effects and baseline number of CH attacks as a covariate. Change from baseline in the overall weekly average number of CH attacks during the 12-week period after administration of the first dose of study drug (based on Week 0 to 12 data) is reported. |
| Mean Change From Baseline in Weekly Average Number of CH Attacks During the 4-Week Period After Administration of the Third Dose of the IMP | Baseline (Week 0), Week 8 up to Week 12 | A CH attack was defined as a severe or very severe unilateral orbital, supraorbital, and/or temporal pain lasting 15 to 180 minutes with either or both of the following 2 categories: 1) at least 1 of the following symptoms or signs, ipsilateral to the headache: -conjunctival injection and/or lacrimation; -nasal congestion and/or rhinorrhea; -eyelid edema; -forehead and facial sweating; -forehead and facial flushing; -sensation of fullness in the ear; -miosis and/or ptosis. 2) a sense of restlessness or agitation. LS mean calculated using MMRM with baseline preventive medication use (yes or no), gender, region (US/Canada or other), treatment, month, and month-by-treatment interaction as fixed effects and baseline number of CH attacks as a covariate. Change from baseline in the overall weekly average number of CH attacks during the 4-week period after administration of the first dose of study drug (based on Week 8 to 12 data) is reported. |
| Mean Change From Baseline in the Weekly Average Number of Days With Use of Cluster-Specific Acute Headache Medications (Triptans and Ergot Compounds) During the 12-Week Period After the First Dose of the IMP | Baseline (Week 0), up to Week 12 | A maximum of 2 concomitant preventive medications for CH were allowed during the study. Participants must have been on a stable dose and regimen of the concomitant medication for at least 2 weeks before screening and throughout the study. LS mean calculated using ANCOVA model with baseline preventive medication use (yes or no), gender, region (US/Canada or other), and treatment as fixed effects and the baseline number of cluster headache attacks as a covariate. Baseline data and the mean change from baseline in the overall weekly average number of days with the use of cluster-specific acute headache medications (triptans and ergot compounds) during the 12-week period after administration of the first dose of study drug (based on Week 0 to 12 data) is reported. |
| Mean Change From Baseline in the Weekly Average Number of Days Oxygen Was Used to Treat Episodic Cluster Headache (ECH) During the 12-Week Period After the First Dose of the IMP | Baseline (Week 0), up to Week 12 | LS mean calculated using ANCOVA model with baseline preventive medication use (yes or no), gender, region (US/Canada or other), and treatment as fixed effects and the baseline number of cluster headache attacks as a covariate. Baseline data and the mean change from baseline in the overall weekly average number of days oxygen was used to treat ECH during the 12-week period after administration of the first dose of IMP (based on Week 0 to 12 data) is reported. |
| Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Baseline, Weeks 1, 4, 8, and 12 | The PPSI assessment was developed to measure pain intensity and was adjusted for CH symptoms improvement. Participants marked the level of CH-associated pain and indicated if pain is 1=much worse, 2=moderately worse, 3=slightly worse, 4=unchanged, 5=slightly improved, 6=moderately improved, or 7=much improved compared with 4 weeks prior. PPSI was defined as the change in pain that corresponds with a minimal rating of 5=slightly improved. Data at Week 1 was recorded on Day 7 in the electronic diary device at home. Week 12 data also included assessment at the early withdrawal visit for participants who discontinued the study early. |
| Number of Participants With Adverse Events (AEs) | Baseline up to Week 12 | An AE was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Relationship of AE to treatment was determined by the Investigator. Serious AEs include death, a life-threatening adverse event, 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 the participant and required medical intervention to prevent the previously listed serious outcomes. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. |
| Number of Participants With Potentially Clinically Significant Laboratory (Serum Chemistry, Hematology, and Urinalysis) Abnormal Results | Baseline up to Week 12 | Serum chemistry, hematology, urinalysis laboratory tests with potentially clinically significant abnormal findings included: alanine aminotransferase (ALP), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH) each ≥3\*upper limit of normal (ULN); blood urea nitrogen (BUN) ≥10.71 millimole (mmol)/L; Bilirubin (Total) ≥34.2 micromole/liter (umol/L); Blood Urea Nitrogen ≥10.71 millimoles (mmol)/L; creatinine ≥177 umol/L; hemoglobin less than or equal to (≤)115 grams (g)/L (males) or ≤95 g/L (females); leukocytes ≥20\*10\^9/L or ≤3\*10\^9/L; eosinophils ≥10%; hematocrit \<0.37 L/L (males) and \<0.32 L/L (females); platelets ≥700\*10\^9/L or ≤75\*10\^9/L; haemoglobin, urine glucose, ketones, urine total protein each ≥2 unit (U) increase from baseline. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. |
| Percentage of Participants With a ≥50% Reduction From Baseline in the Weekly Average Number of CH Attacks During the 4-Week Period After the First Dose of the IMP | Baseline (Week 0), up to Week 4 | A CH attack was defined as a severe or very severe unilateral orbital, supraorbital, and/or temporal pain lasting 15 to 180 minutes with either or both of the following 2 categories: 1) at least 1 of the following symptoms or signs, ipsilateral to the headache: -conjunctival injection and/or lacrimation; -nasal congestion and/or rhinorrhea; -eyelid edema; -forehead and facial sweating; -forehead and facial flushing; -sensation of fullness in the ear; -miosis and/or ptosis. 2) a sense of restlessness or agitation. |
| Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values | Baseline up to Week 12 | Potentially clinically significant abnormal vital signs findings included: pulse rate ≥120 beats per minute (bpm) and increase of 15 bpm; systolic blood pressure ≤90 millimeters of mercury (mmHg) and decrease of 20 mmHg; diastolic blood pressure ≤50 mmHg and decrease of 15 mmHg, or ≥105 mmHg and increase of 15 mmHg. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. |
| Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters | Baseline up to Week 12 | ECG parameters included: heart rate, PR interval, QRS interval, QT interval corrected using the Fridericia formula (QTcF), QT interval corrected using the Bazett's formula (QTcB) and RR interval. Shifts represented as Baseline - endpoint value (last observed post-baseline value). Abnormal NCS indicated an abnormal but not clinically significant finding. Abnormal CS indicated an abnormal and clinically significant finding. Missing ECG shift data are also presented. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. |
| Number of Participants Who Received Concomitant Medications | Baseline up to Week 12 | Concomitant medications included: agents acting on the renin-angiotensin system, all other therapeutic products (for example: homeopathic preparation), allergens, analgesics, anesthetics, anti-parkinson drugs, antianemic preparations, antibacterials for systemic use, antibiotics and chemotherapeutics for dermatological use, antidiarrheals, intestinal antiinflammatory/antiinfective agents, antiemetic, antiepileptics, antifungals for dermatologiocal use, antigout preparations, antihemorrhagics, antihistamines for systemic use, antihypertensives, antiinflammatory and antirheumatic products, antimycotics for systemic use, antipruritics, antipsoriatics, antivirals for systemic use, beta blocking agents, blood substitutes and perfusion solutions, cardiac therapy, corticosteroids, cough and cold preparations, diagnostic radiopharmaceuticals, diuretics, thyroid therapy, urologicals, vaccines, psycoleptics, psycoanaleptics, ophthalmologicals, muscle relaxants, drugs used in diabetes etc. |
| Number of Participants With Injection Site Reactions | Baseline up to Week 12 | Number of participants who reported treatment-emergent injection site reactions are summarized. Preferred terms from Medical Dictionary for Regulatory Activities (MedDRA) version 18.1 were offered without a threshold applied. Injection site reactions included injection site erythema, induration, pain, haemorrhage, swelling, and pruritus. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. |
| Number of Participants With Hypersensitivity/Anaphylaxis Reactions | Baseline up to Week 12 | A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. |
| Number of Participants With Suicidal Ideation and Suicidal Behavior as Assessed by the Electronic Columbia Suicide Severity Rating Scale (eC-SSRS) | Baseline up to Week 12 | eC-SSRS is a questionnaire to assess suicidal ideation and suicidal behavior. Suicidal behavior was defined as a yes answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation was defined as a yes answer to any one of 5 suicidal ideation questions: wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent, any self-injurious behavior with no suicidal intent. |
| Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Baseline up to Week 12 | Coagulation parameters included: prothrombin time (PT) (seconds) and prothrombin international normalized ratio (INR). Shifts represented as Baseline - endpoint value (last observed post-baseline value). Shifts from baseline to endpoint were summarized using participant counts grouped into three categories: - Low (below normal range) - Normal (within the normal range of 9.4 to 12.5 seconds) - High (above normal range). Missing PT and prothrombin INR shift data are also presented. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. |
Countries
Australia, Canada, Finland, Germany, Israel, Italy, Netherlands, Poland, Spain, Sweden, United Kingdom, United States
Participant flow
Pre-assignment details
A total of 169 participants were randomized in a 1:1:1 ratio to placebo, fremanezumab 675 milligrams (mg)/placebo/placebo, or fremanezumab 900/225/225 mg groups.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo administered via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injection at Weeks 4 and 8, respectively. | 59 |
| Fremanezumab 675 mg/Placebo/Placebo Participants received placebo as an approximately 1-hour intravenous infusion followed by fremanezumab at 675 mg administered as 3 subcutaneous injections (225 mg/1.5 mL) at Week 0 and placebo administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively. | 55 |
| Fremanezumab 900/225/225 mg Participants received fremanezumab at 900 mg administered via an approximately 1-hour intravenous infusion followed by 3 placebo subcutaneous injections at Week 0 and fremanezumab at 225 mg administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively. | 55 |
| Total | 169 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 2 |
| Overall Study | Lack of Efficacy | 1 | 2 | 1 |
| Overall Study | Lost to Follow-up | 1 | 1 | 0 |
| Overall Study | Other than specified | 5 | 4 | 7 |
| Overall Study | Protocol Violation | 2 | 3 | 2 |
| Overall Study | Withdrawal by Subject | 3 | 3 | 3 |
Baseline characteristics
| Characteristic | Fremanezumab 900/225/225 mg | Placebo | Fremanezumab 675 mg/Placebo/Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 43.5 years STANDARD_DEVIATION 11.48 | 43.1 years STANDARD_DEVIATION 10.39 | 45.4 years STANDARD_DEVIATION 11.23 | 43.9 years STANDARD_DEVIATION 11.01 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 2 Participants | 3 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 49 Participants | 56 Participants | 52 Participants | 157 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Number of CH Attacks | 14.5 CH attacks STANDARD_DEVIATION 7.55 | 14.8 CH attacks STANDARD_DEVIATION 10.5 | 15.9 CH attacks STANDARD_DEVIATION 9.18 | 15.1 CH attacks STANDARD_DEVIATION 9.15 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 3 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 51 Participants | 54 Participants | 55 Participants | 160 Participants |
| Sex: Female, Male Female | 17 Participants | 16 Participants | 17 Participants | 50 Participants |
| Sex: Female, Male Male | 38 Participants | 43 Participants | 38 Participants | 119 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 59 | 0 / 55 | 0 / 55 |
| other Total, other adverse events | 7 / 59 | 9 / 55 | 16 / 55 |
| serious Total, serious adverse events | 5 / 59 | 0 / 55 | 1 / 55 |
Outcome results
Primary
Mean Change From Baseline in the Weekly Average Number of Cluster Headache (CH) Attacks During the 4-Week Period After Administration of the First Dose of the IMP
A CH attack was defined as a severe or very severe unilateral orbital, supraorbital, and/or temporal pain lasting 15 to 180 minutes with either or both of the following 2 categories: 1) at least 1 of the following symptoms or signs, ipsilateral to the headache: -conjunctival injection and/or lacrimation; -nasal congestion and/or rhinorrhea; -eyelid edema; -forehead and facial sweating; -forehead and facial flushing; -sensation of fullness in the ear; -miosis and/or ptosis. 2) a sense of restlessness or agitation. Least Squares (LS) mean calculated using analysis of covariance (ANCOVA) model with baseline preventive medication use (yes or no), sex, region (United States \[US\]/Canada or other), and treatment as fixed effects and the baseline number of CH attacks as a covariate. Change from baseline in the overall weekly average number of CH attacks during the 4-week period after administration of the first dose of study drug (based on Week 0 to 4 data) is reported.
Time frame: Baseline (Week 0), up to Week 4
Population: Full analysis set included all randomized participants who received at least 1 dose of IMP and had at least 10 days of postbaseline efficacy assessment in the first 4 weeks on the primary endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in the Weekly Average Number of Cluster Headache (CH) Attacks During the 4-Week Period After Administration of the First Dose of the IMP | -5.7 CH attacks/week | Standard Error 1 |
| Fremanezumab 675 mg/Placebo/Placebo | Mean Change From Baseline in the Weekly Average Number of Cluster Headache (CH) Attacks During the 4-Week Period After Administration of the First Dose of the IMP | -5.8 CH attacks/week | Standard Error 1.02 |
| Fremanezumab 900/225/225 mg | Mean Change From Baseline in the Weekly Average Number of Cluster Headache (CH) Attacks During the 4-Week Period After Administration of the First Dose of the IMP | -7.6 CH attacks/week | Standard Error 1.01 |
p-value: 0.909395% CI: [-2.72, 2.42]ANCOVA
p-value: 0.134595% CI: [-4.49, 0.61]ANCOVA
Secondary
Mean Change From Baseline in the Weekly Average Number of Days Oxygen Was Used to Treat Episodic Cluster Headache (ECH) During the 12-Week Period After the First Dose of the IMP
LS mean calculated using ANCOVA model with baseline preventive medication use (yes or no), gender, region (US/Canada or other), and treatment as fixed effects and the baseline number of cluster headache attacks as a covariate. Baseline data and the mean change from baseline in the overall weekly average number of days oxygen was used to treat ECH during the 12-week period after administration of the first dose of IMP (based on Week 0 to 12 data) is reported.
Time frame: Baseline (Week 0), up to Week 12
Population: Full analysis set included all randomized participants who received at least 1 dose of IMP and had at least 10 days of postbaseline efficacy assessment in the first 4 weeks on the primary endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in the Weekly Average Number of Days Oxygen Was Used to Treat Episodic Cluster Headache (ECH) During the 12-Week Period After the First Dose of the IMP | -1.1 days of use/week | Standard Error 0.3 |
| Fremanezumab 675 mg/Placebo/Placebo | Mean Change From Baseline in the Weekly Average Number of Days Oxygen Was Used to Treat Episodic Cluster Headache (ECH) During the 12-Week Period After the First Dose of the IMP | -1.5 days of use/week | Standard Error 0.31 |
| Fremanezumab 900/225/225 mg | Mean Change From Baseline in the Weekly Average Number of Days Oxygen Was Used to Treat Episodic Cluster Headache (ECH) During the 12-Week Period After the First Dose of the IMP | -1.0 days of use/week | Standard Error 0.3 |
Secondary
Mean Change From Baseline in the Weekly Average Number of Days With Use of Cluster-Specific Acute Headache Medications (Triptans and Ergot Compounds) During the 12-Week Period After the First Dose of the IMP
A maximum of 2 concomitant preventive medications for CH were allowed during the study. Participants must have been on a stable dose and regimen of the concomitant medication for at least 2 weeks before screening and throughout the study. LS mean calculated using ANCOVA model with baseline preventive medication use (yes or no), gender, region (US/Canada or other), and treatment as fixed effects and the baseline number of cluster headache attacks as a covariate. Baseline data and the mean change from baseline in the overall weekly average number of days with the use of cluster-specific acute headache medications (triptans and ergot compounds) during the 12-week period after administration of the first dose of study drug (based on Week 0 to 12 data) is reported.
Time frame: Baseline (Week 0), up to Week 12
Population: Full analysis set included all randomized participants who received at least 1 dose of IMP and had at least 10 days of postbaseline efficacy assessment in the first 4 weeks on the primary endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in the Weekly Average Number of Days With Use of Cluster-Specific Acute Headache Medications (Triptans and Ergot Compounds) During the 12-Week Period After the First Dose of the IMP | -1.6 days of use/week | Standard Error 0.36 |
| Fremanezumab 675 mg/Placebo/Placebo | Mean Change From Baseline in the Weekly Average Number of Days With Use of Cluster-Specific Acute Headache Medications (Triptans and Ergot Compounds) During the 12-Week Period After the First Dose of the IMP | -2.4 days of use/week | Standard Error 0.36 |
| Fremanezumab 900/225/225 mg | Mean Change From Baseline in the Weekly Average Number of Days With Use of Cluster-Specific Acute Headache Medications (Triptans and Ergot Compounds) During the 12-Week Period After the First Dose of the IMP | -2.8 days of use/week | Standard Error 0.36 |
Secondary
Mean Change From Baseline in Weekly Average Number of CH Attacks During the 12-Week Period After Administration of the First Dose of the IMP
A CH attack was defined as a severe or very severe unilateral orbital, supraorbital, and/or temporal pain lasting 15 to 180 minutes with either or both of the following 2 categories: 1) at least 1 of the following symptoms or signs, ipsilateral to the headache: -conjunctival injection and/or lacrimation; -nasal congestion and/or rhinorrhea; -eyelid edema; -forehead and facial sweating; -forehead and facial flushing; -sensation of fullness in the ear; -miosis and/or ptosis. 2) a sense of restlessness or agitation. LS mean calculated using mixed model for repeated measures (MMRM) with baseline preventive medication use (yes or no), gender, region (US/Canada or other), treatment, month, and month-by-treatment interaction as fixed effects and baseline number of CH attacks as a covariate. Change from baseline in the overall weekly average number of CH attacks during the 12-week period after administration of the first dose of study drug (based on Week 0 to 12 data) is reported.
Time frame: Baseline (Week 0), up to Week 12
Population: Full analysis set included all randomized participants who received at least 1 dose of IMP and had at least 10 days of postbaseline efficacy assessment in the first 4 weeks on the primary endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in Weekly Average Number of CH Attacks During the 12-Week Period After Administration of the First Dose of the IMP | -8.4 CH attacks/week | Standard Error 0.66 |
| Fremanezumab 675 mg/Placebo/Placebo | Mean Change From Baseline in Weekly Average Number of CH Attacks During the 12-Week Period After Administration of the First Dose of the IMP | -8.9 CH attacks/week | Standard Error 0.68 |
| Fremanezumab 900/225/225 mg | Mean Change From Baseline in Weekly Average Number of CH Attacks During the 12-Week Period After Administration of the First Dose of the IMP | -9.6 CH attacks/week | Standard Error 0.67 |
Secondary
Mean Change From Baseline in Weekly Average Number of CH Attacks During the 4-Week Period After Administration of the Third Dose of the IMP
A CH attack was defined as a severe or very severe unilateral orbital, supraorbital, and/or temporal pain lasting 15 to 180 minutes with either or both of the following 2 categories: 1) at least 1 of the following symptoms or signs, ipsilateral to the headache: -conjunctival injection and/or lacrimation; -nasal congestion and/or rhinorrhea; -eyelid edema; -forehead and facial sweating; -forehead and facial flushing; -sensation of fullness in the ear; -miosis and/or ptosis. 2) a sense of restlessness or agitation. LS mean calculated using MMRM with baseline preventive medication use (yes or no), gender, region (US/Canada or other), treatment, month, and month-by-treatment interaction as fixed effects and baseline number of CH attacks as a covariate. Change from baseline in the overall weekly average number of CH attacks during the 4-week period after administration of the first dose of study drug (based on Week 8 to 12 data) is reported.
Time frame: Baseline (Week 0), Week 8 up to Week 12
Population: Full analysis set included all randomized participants who received at least 1 dose of IMP and had at least 10 days of postbaseline efficacy assessment in the first 4 weeks on the primary endpoint. Here, 'overall number of participants analyzed'=participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in Weekly Average Number of CH Attacks During the 4-Week Period After Administration of the Third Dose of the IMP | -10.8 CH attacks/week | Standard Error 0.75 |
| Fremanezumab 675 mg/Placebo/Placebo | Mean Change From Baseline in Weekly Average Number of CH Attacks During the 4-Week Period After Administration of the Third Dose of the IMP | -10.8 CH attacks/week | Standard Error 0.78 |
| Fremanezumab 900/225/225 mg | Mean Change From Baseline in Weekly Average Number of CH Attacks During the 4-Week Period After Administration of the Third Dose of the IMP | -10.9 CH attacks/week | Standard Error 0.78 |
Secondary
Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12
The PPSI assessment was developed to measure pain intensity and was adjusted for CH symptoms improvement. Participants marked the level of CH-associated pain and indicated if pain is 1=much worse, 2=moderately worse, 3=slightly worse, 4=unchanged, 5=slightly improved, 6=moderately improved, or 7=much improved compared with 4 weeks prior. PPSI was defined as the change in pain that corresponds with a minimal rating of 5=slightly improved. Data at Week 1 was recorded on Day 7 in the electronic diary device at home. Week 12 data also included assessment at the early withdrawal visit for participants who discontinued the study early.
Time frame: Baseline, Weeks 1, 4, 8, and 12
Population: Full analysis set included all randomized participants who received at least 1 dose of IMP and had at least 10 days of postbaseline efficacy assessment in the first 4 weeks on the primary endpoint.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Baseline | Much worse | 10 Participants |
| Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 8 | Unchanged | 13 Participants |
| Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 1 | Moderately worse | 2 Participants |
| Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 8 | Slightly improved | 1 Participants |
| Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 8 | Moderately improved | 7 Participants |
| Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Baseline | Unchanged | 37 Participants |
| Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 8 | Much improved | 20 Participants |
| Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 1 | Slightly worse | 5 Participants |
| Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 8 | Missing | 12 Participants |
| Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 12 | Much worse | 3 Participants |
| Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 12 | Moderately worse | 0 Participants |
| Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 1 | Unchanged | 19 Participants |
| Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 12 | Slightly worse | 2 Participants |
| Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 12 | Unchanged | 16 Participants |
| Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Baseline | Moderately worse | 3 Participants |
| Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 12 | Slightly improved | 5 Participants |
| Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 1 | Slightly improved | 11 Participants |
| Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 12 | Moderately improved | 8 Participants |
| Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 12 | Much improved | 17 Participants |
| Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Baseline | Slightly improved | 3 Participants |
| Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 12 | Missing | 6 Participants |
| Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 1 | Moderately improved | 5 Participants |
| Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 1 | Much improved | 6 Participants |
| Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 1 | Missing | 7 Participants |
| Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Baseline | Moderately improved | 1 Participants |
| Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 4 | Much worse | 1 Participants |
| Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 4 | Moderately worse | 3 Participants |
| Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 4 | Slightly worse | 4 Participants |
| Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Baseline | Much improved | 0 Participants |
| Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 4 | Unchanged | 8 Participants |
| Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 4 | Slightly improved | 9 Participants |
| Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Baseline | Slightly worse | 3 Participants |
| Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 4 | Moderately improved | 5 Participants |
| Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Baseline | Missing | 0 Participants |
| Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 4 | Much improved | 23 Participants |
| Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 4 | Missing | 4 Participants |
| Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 8 | Much worse | 1 Participants |
| Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 1 | Much worse | 2 Participants |
| Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 8 | Moderately worse | 3 Participants |
| Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 8 | Slightly worse | 0 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 4 | Slightly improved | 9 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 1 | Moderately improved | 3 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 8 | Unchanged | 8 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Baseline | Slightly improved | 0 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Baseline | Slightly worse | 3 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 8 | Slightly improved | 6 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 1 | Moderately worse | 2 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 1 | Much improved | 12 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 8 | Moderately improved | 6 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Baseline | Moderately worse | 5 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 8 | Moderately worse | 0 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 8 | Much improved | 20 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 1 | Missing | 10 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 4 | Moderately improved | 7 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 8 | Missing | 11 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 1 | Slightly worse | 3 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 8 | Much worse | 1 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 12 | Much worse | 2 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Baseline | Unchanged | 31 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 4 | Much worse | 1 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 12 | Moderately worse | 0 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Baseline | Moderately improved | 0 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 1 | Much worse | 4 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 12 | Slightly worse | 1 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 1 | Unchanged | 11 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 4 | Moderately worse | 0 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 12 | Unchanged | 16 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Baseline | Much worse | 14 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 4 | Much improved | 19 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 12 | Slightly improved | 5 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Baseline | Missing | 0 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 8 | Slightly worse | 1 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 12 | Moderately improved | 7 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 1 | Slightly improved | 8 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 4 | Unchanged | 11 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 12 | Much improved | 19 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Baseline | Much improved | 0 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 4 | Missing | 4 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 12 | Missing | 3 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 4 | Slightly worse | 2 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 12 | Missing | 3 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Baseline | Much worse | 7 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Baseline | Moderately worse | 8 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Baseline | Slightly worse | 3 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Baseline | Unchanged | 28 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Baseline | Slightly improved | 6 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Baseline | Moderately improved | 1 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Baseline | Much improved | 2 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Baseline | Missing | 0 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 1 | Much worse | 1 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 1 | Moderately worse | 1 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 1 | Slightly worse | 2 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 1 | Unchanged | 9 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 1 | Slightly improved | 14 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 1 | Moderately improved | 6 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 1 | Much improved | 12 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 1 | Missing | 10 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 4 | Much worse | 2 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 4 | Moderately worse | 1 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 4 | Slightly worse | 0 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 4 | Unchanged | 5 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 4 | Slightly improved | 8 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 4 | Moderately improved | 8 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 4 | Much improved | 27 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 4 | Missing | 4 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 8 | Much worse | 0 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 8 | Moderately worse | 1 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 8 | Slightly worse | 1 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 8 | Unchanged | 12 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 8 | Slightly improved | 5 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 8 | Moderately improved | 7 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 8 | Much improved | 17 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 8 | Missing | 12 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 12 | Much worse | 2 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 12 | Moderately worse | 1 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 12 | Slightly worse | 0 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 12 | Unchanged | 16 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 12 | Slightly improved | 4 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 12 | Moderately improved | 5 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 | Week 12 | Much improved | 24 Participants |
Secondary
Number of Participants Who Received Concomitant Medications
Concomitant medications included: agents acting on the renin-angiotensin system, all other therapeutic products (for example: homeopathic preparation), allergens, analgesics, anesthetics, anti-parkinson drugs, antianemic preparations, antibacterials for systemic use, antibiotics and chemotherapeutics for dermatological use, antidiarrheals, intestinal antiinflammatory/antiinfective agents, antiemetic, antiepileptics, antifungals for dermatologiocal use, antigout preparations, antihemorrhagics, antihistamines for systemic use, antihypertensives, antiinflammatory and antirheumatic products, antimycotics for systemic use, antipruritics, antipsoriatics, antivirals for systemic use, beta blocking agents, blood substitutes and perfusion solutions, cardiac therapy, corticosteroids, cough and cold preparations, diagnostic radiopharmaceuticals, diuretics, thyroid therapy, urologicals, vaccines, psycoleptics, psycoanaleptics, ophthalmologicals, muscle relaxants, drugs used in diabetes etc.
Time frame: Baseline up to Week 12
Population: Safety analysis set included all randomized participants who received at least 1 dose of the IMP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Who Received Concomitant Medications | 57 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants Who Received Concomitant Medications | 52 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants Who Received Concomitant Medications | 52 Participants |
Secondary
Number of Participants With Adverse Events (AEs)
An AE was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Relationship of AE to treatment was determined by the Investigator. Serious AEs include death, a life-threatening adverse event, 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 the participant and required medical intervention to prevent the previously listed serious outcomes. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time frame: Baseline up to Week 12
Population: Safety analysis set included all randomized participants who received at least 1 dose of the IMP.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Adverse Events (AEs) | Serious AEs | 5 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) | Any AEs | 28 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) | AEs leading to discontinuation | 1 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) | Treatment-related AEs | 8 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Adverse Events (AEs) | Serious AEs | 0 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Adverse Events (AEs) | Treatment-related AEs | 11 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Adverse Events (AEs) | AEs leading to discontinuation | 0 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Adverse Events (AEs) | Any AEs | 26 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Adverse Events (AEs) | AEs leading to discontinuation | 2 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Adverse Events (AEs) | Any AEs | 28 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Adverse Events (AEs) | Treatment-related AEs | 13 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Adverse Events (AEs) | Serious AEs | 1 Participants |
Secondary
Number of Participants With Hypersensitivity/Anaphylaxis Reactions
A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time frame: Baseline up to Week 12
Population: Safety analysis set included all randomized participants who received at least 1 dose of the IMP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Hypersensitivity/Anaphylaxis Reactions | 0 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Hypersensitivity/Anaphylaxis Reactions | 0 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Hypersensitivity/Anaphylaxis Reactions | 0 Participants |
Secondary
Number of Participants With Injection Site Reactions
Number of participants who reported treatment-emergent injection site reactions are summarized. Preferred terms from Medical Dictionary for Regulatory Activities (MedDRA) version 18.1 were offered without a threshold applied. Injection site reactions included injection site erythema, induration, pain, haemorrhage, swelling, and pruritus. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time frame: Baseline up to Week 12
Population: Safety analysis set included all randomized participants who received at least 1 dose of the IMP.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Injection Site Reactions | Injection site pruritus | 1 Participants |
| Placebo | Number of Participants With Injection Site Reactions | Injection site pain | 4 Participants |
| Placebo | Number of Participants With Injection Site Reactions | Injection site swelling | 0 Participants |
| Placebo | Number of Participants With Injection Site Reactions | Injection site erythema | 2 Participants |
| Placebo | Number of Participants With Injection Site Reactions | Injection site haemorrhage | 0 Participants |
| Placebo | Number of Participants With Injection Site Reactions | Injection site induration | 1 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Injection Site Reactions | Injection site induration | 3 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Injection Site Reactions | Injection site pruritus | 0 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Injection Site Reactions | Injection site haemorrhage | 0 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Injection Site Reactions | Injection site erythema | 0 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Injection Site Reactions | Injection site swelling | 1 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Injection Site Reactions | Injection site pain | 2 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Injection Site Reactions | Injection site swelling | 0 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Injection Site Reactions | Injection site induration | 6 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Injection Site Reactions | Injection site pain | 6 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Injection Site Reactions | Injection site haemorrhage | 1 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Injection Site Reactions | Injection site pruritus | 1 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Injection Site Reactions | Injection site erythema | 2 Participants |
Secondary
Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values
Potentially clinically significant abnormal vital signs findings included: pulse rate ≥120 beats per minute (bpm) and increase of 15 bpm; systolic blood pressure ≤90 millimeters of mercury (mmHg) and decrease of 20 mmHg; diastolic blood pressure ≤50 mmHg and decrease of 15 mmHg, or ≥105 mmHg and increase of 15 mmHg. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time frame: Baseline up to Week 12
Population: Safety analysis set included all randomized participants who received at least 1 dose of the IMP. Here, 'overall number of participants analyzed'=participants evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values | 3 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values | 0 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values | 1 Participants |
Secondary
Number of Participants With Potentially Clinically Significant Laboratory (Serum Chemistry, Hematology, and Urinalysis) Abnormal Results
Serum chemistry, hematology, urinalysis laboratory tests with potentially clinically significant abnormal findings included: alanine aminotransferase (ALP), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH) each ≥3\*upper limit of normal (ULN); blood urea nitrogen (BUN) ≥10.71 millimole (mmol)/L; Bilirubin (Total) ≥34.2 micromole/liter (umol/L); Blood Urea Nitrogen ≥10.71 millimoles (mmol)/L; creatinine ≥177 umol/L; hemoglobin less than or equal to (≤)115 grams (g)/L (males) or ≤95 g/L (females); leukocytes ≥20\*10\^9/L or ≤3\*10\^9/L; eosinophils ≥10%; hematocrit \<0.37 L/L (males) and \<0.32 L/L (females); platelets ≥700\*10\^9/L or ≤75\*10\^9/L; haemoglobin, urine glucose, ketones, urine total protein each ≥2 unit (U) increase from baseline. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time frame: Baseline up to Week 12
Population: Safety analysis set included all randomized participants who received at least 1 dose of the IMP. Here, 'overall number of participants analyzed'=participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Potentially Clinically Significant Laboratory (Serum Chemistry, Hematology, and Urinalysis) Abnormal Results | With at least 1 hematology abnormality | 4 Participants |
| Placebo | Number of Participants With Potentially Clinically Significant Laboratory (Serum Chemistry, Hematology, and Urinalysis) Abnormal Results | With at least 1 serum chemistry abnormality | 1 Participants |
| Placebo | Number of Participants With Potentially Clinically Significant Laboratory (Serum Chemistry, Hematology, and Urinalysis) Abnormal Results | With at least 1 urinalysis abnormality | 0 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Potentially Clinically Significant Laboratory (Serum Chemistry, Hematology, and Urinalysis) Abnormal Results | With at least 1 hematology abnormality | 1 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Potentially Clinically Significant Laboratory (Serum Chemistry, Hematology, and Urinalysis) Abnormal Results | With at least 1 serum chemistry abnormality | 1 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Potentially Clinically Significant Laboratory (Serum Chemistry, Hematology, and Urinalysis) Abnormal Results | With at least 1 urinalysis abnormality | 0 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Potentially Clinically Significant Laboratory (Serum Chemistry, Hematology, and Urinalysis) Abnormal Results | With at least 1 serum chemistry abnormality | 0 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Potentially Clinically Significant Laboratory (Serum Chemistry, Hematology, and Urinalysis) Abnormal Results | With at least 1 urinalysis abnormality | 0 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Potentially Clinically Significant Laboratory (Serum Chemistry, Hematology, and Urinalysis) Abnormal Results | With at least 1 hematology abnormality | 4 Participants |
Secondary
Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results
Coagulation parameters included: prothrombin time (PT) (seconds) and prothrombin international normalized ratio (INR). Shifts represented as Baseline - endpoint value (last observed post-baseline value). Shifts from baseline to endpoint were summarized using participant counts grouped into three categories: - Low (below normal range) - Normal (within the normal range of 9.4 to 12.5 seconds) - High (above normal range). Missing PT and prothrombin INR shift data are also presented. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time frame: Baseline up to Week 12
Population: Safety analysis set included all randomized participants who received at least 1 dose of the IMP.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Placebo | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Normal-Normal | 48 Participants |
| Placebo | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | High-Normal | 4 Participants |
| Placebo | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Low-Low | 0 Participants |
| Placebo | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Normal-Low | 0 Participants |
| Placebo | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | High-High | 1 Participants |
| Placebo | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Normal-Low | 0 Participants |
| Placebo | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Low-High | 0 Participants |
| Placebo | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Missing | 5 Participants |
| Placebo | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Missing | 5 Participants |
| Placebo | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Low-Normal | 0 Participants |
| Placebo | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Low-Low | 0 Participants |
| Placebo | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | High-Normal | 3 Participants |
| Placebo | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Normal-Normal | 47 Participants |
| Placebo | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | High-High | 1 Participants |
| Placebo | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | High-Low | 0 Participants |
| Placebo | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Normal-High | 2 Participants |
| Placebo | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Low-High | 0 Participants |
| Placebo | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Normal-High | 2 Participants |
| Placebo | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | High-Low | 0 Participants |
| Placebo | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Low-Normal | 0 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | High-Normal | 3 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Low-Low | 0 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Low-Normal | 0 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Low-High | 0 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Normal-Low | 0 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Normal-Normal | 46 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Normal-High | 2 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | High-Low | 0 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | High-Normal | 4 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | High-High | 1 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Missing | 2 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Low-Low | 0 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Low-Normal | 0 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Low-High | 0 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Normal-Low | 0 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Normal-Normal | 48 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Normal-High | 2 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | High-Low | 0 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | High-High | 0 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Missing | 2 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Low-Normal | 0 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Normal-Low | 0 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | High-Low | 0 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Missing | 2 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Normal-Normal | 47 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Normal-High | 3 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | High-High | 2 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Normal-High | 1 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Normal-Normal | 44 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Low-Low | 0 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | High-Low | 0 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Normal-Low | 0 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Low-Low | 0 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Missing | 2 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Low-High | 0 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Low-Normal | 0 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | High-High | 2 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | High-Normal | 3 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Low-High | 0 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | High-Normal | 4 Participants |
Secondary
Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters
ECG parameters included: heart rate, PR interval, QRS interval, QT interval corrected using the Fridericia formula (QTcF), QT interval corrected using the Bazett's formula (QTcB) and RR interval. Shifts represented as Baseline - endpoint value (last observed post-baseline value). Abnormal NCS indicated an abnormal but not clinically significant finding. Abnormal CS indicated an abnormal and clinically significant finding. Missing ECG shift data are also presented. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time frame: Baseline up to Week 12
Population: Safety analysis set included all randomized participants who received at least 1 dose of the IMP.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters | Abnormal CS / Normal | 0 Participants |
| Placebo | Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters | Normal / Abnormal CS | 0 Participants |
| Placebo | Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters | Abnormal CS / Abnormal NCS | 0 Participants |
| Placebo | Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters | Abnormal CS / Abnormal CS | 0 Participants |
| Placebo | Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters | Normal / Normal | 35 Participants |
| Placebo | Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters | Missing | 7 Participants |
| Placebo | Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters | Abnormal NCS / Normal | 4 Participants |
| Placebo | Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters | Normal / Abnormal NCS | 6 Participants |
| Placebo | Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters | Abnormal NCS / Abnormal NCS | 7 Participants |
| Placebo | Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters | Abnormal NCS / Abnormal CS | 0 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters | Abnormal CS / Normal | 0 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters | Abnormal NCS / Normal | 9 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters | Abnormal NCS / Abnormal CS | 0 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters | Abnormal CS / Abnormal NCS | 0 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters | Normal / Abnormal CS | 0 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters | Normal / Normal | 33 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters | Abnormal CS / Abnormal CS | 0 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters | Abnormal NCS / Abnormal NCS | 9 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters | Normal / Abnormal NCS | 1 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters | Missing | 3 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters | Missing | 5 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters | Normal / Normal | 23 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters | Normal / Abnormal NCS | 5 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters | Normal / Abnormal CS | 0 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters | Abnormal NCS / Normal | 4 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters | Abnormal NCS / Abnormal NCS | 18 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters | Abnormal NCS / Abnormal CS | 0 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters | Abnormal CS / Normal | 0 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters | Abnormal CS / Abnormal NCS | 0 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters | Abnormal CS / Abnormal CS | 0 Participants |
Secondary
Number of Participants With Suicidal Ideation and Suicidal Behavior as Assessed by the Electronic Columbia Suicide Severity Rating Scale (eC-SSRS)
eC-SSRS is a questionnaire to assess suicidal ideation and suicidal behavior. Suicidal behavior was defined as a yes answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation was defined as a yes answer to any one of 5 suicidal ideation questions: wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent, any self-injurious behavior with no suicidal intent.
Time frame: Baseline up to Week 12
Population: Safety analysis set included all randomized participants who received at least 1 dose of the IMP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Suicidal Ideation and Suicidal Behavior as Assessed by the Electronic Columbia Suicide Severity Rating Scale (eC-SSRS) | 0 Participants |
| Fremanezumab 675 mg/Placebo/Placebo | Number of Participants With Suicidal Ideation and Suicidal Behavior as Assessed by the Electronic Columbia Suicide Severity Rating Scale (eC-SSRS) | 1 Participants |
| Fremanezumab 900/225/225 mg | Number of Participants With Suicidal Ideation and Suicidal Behavior as Assessed by the Electronic Columbia Suicide Severity Rating Scale (eC-SSRS) | 4 Participants |
Secondary
Percentage of Participants With a ≥50% Reduction From Baseline in the Weekly Average Number of CH Attacks During the 4-Week Period After the First Dose of the IMP
A CH attack was defined as a severe or very severe unilateral orbital, supraorbital, and/or temporal pain lasting 15 to 180 minutes with either or both of the following 2 categories: 1) at least 1 of the following symptoms or signs, ipsilateral to the headache: -conjunctival injection and/or lacrimation; -nasal congestion and/or rhinorrhea; -eyelid edema; -forehead and facial sweating; -forehead and facial flushing; -sensation of fullness in the ear; -miosis and/or ptosis. 2) a sense of restlessness or agitation.
Time frame: Baseline (Week 0), up to Week 4
Population: Full analysis set included all randomized participants who received at least 1 dose of IMP and had at least 10 days of postbaseline efficacy assessment in the first 4 weeks on the primary endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With a ≥50% Reduction From Baseline in the Weekly Average Number of CH Attacks During the 4-Week Period After the First Dose of the IMP | 60 percentage of participants |
| Fremanezumab 675 mg/Placebo/Placebo | Percentage of Participants With a ≥50% Reduction From Baseline in the Weekly Average Number of CH Attacks During the 4-Week Period After the First Dose of the IMP | 55 percentage of participants |
| Fremanezumab 900/225/225 mg | Percentage of Participants With a ≥50% Reduction From Baseline in the Weekly Average Number of CH Attacks During the 4-Week Period After the First Dose of the IMP | 75 percentage of participants |