A Study to Explore the Long-Term Safety and Efficacy of Fremanezumab (TEV-48125) for the Prevention of Cluster Headache

Concomitant medications included: agents acting on the renin-angiotensin system, all other therapeutic products (homeopathic), allergens, analgesics, anesthetics, anti-parkinson drugs, antianemic preparations, antibacterials, 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. Baseline refers to values from the pivotal studies.

Time frame: Baseline up to follow-up (Week 68)

Population: Safety analysis set included all participants who received at least 1 dose of study drug.

A complete physical examination included the following organ systems: general appearance; head, eyes, ears, nose, and throat; chest and lungs; heart; abdomen; musculoskeletal; skin; lymph nodes; and neurological. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. Baseline refers to the baseline values from the pivotal studies.

Time frame: Baseline up to follow-up (Week 68)

Population: ITT analysis set included all participants who were enrolled in this study for long-term safety evaluation, regardless if they received study treatment or not.

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. Baseline refers to the baseline values from the pivotal studies.

Time frame: Baseline up to follow-up (Week 68)

Population: Safety analysis set included all participants who received at least 1 dose of study drug.

A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. Baseline refers to the baseline values from the pivotal studies.

Time frame: Baseline up to Week 36

Population: Safety analysis set included all participants who received at least 1 dose of study drug.

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, bruising, rash, warmth, and pruritus. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. Baseline refers to the baseline values from the pivotal studies.

Time frame: Baseline up to Week 36

Population: Safety analysis set included all participants who received at least 1 dose of study drug.

Hematology tests with potentially clinically significant abnormal findings included: hemoglobin less than or equal to (≤)115 grams (g)/L (males) or ≤95 g/L (females), leukocytes count ≥20\*10\^9/L or ≤3\*10\^9/L, eosinophils ≥10%, hematocrit \<0.37 L/L (males) and \<0.32 L/L (females), platelets count ≥700\*10\^9/L or ≤75\*10\^9/L, absolute neutrophil count (ANC) ≤1\*10\^9/L. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. Baseline refers to the baseline values from the pivotal studies.

Time frame: Baseline up to end of treatment (Week 40)

Population: Safety analysis set included all participants who received at least 1 dose of study drug. Here, 'Overall number of participants analyzed' signifies participants with a laboratory result.

Serum chemistry tests with potentially clinically significant abnormal findings included: alanine aminotransferase (ALT), 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); and Creatinine ≥177 umol/L. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. Baseline refers to the baseline values from the pivotal studies.

Time frame: Baseline up to end of treatment (Week 40)

Population: Safety analysis set included all participants who received at least 1 dose of study drug. Here, 'Overall number of participants analyzed' signifies participants with a laboratory result.

Urinalysis laboratory tests with potentially clinically significant abnormal findings included: 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. Baseline refers to the baseline values from the pivotal studies.

Time frame: Baseline up to end of treatment (Week 40)

Population: Safety analysis set included all participants who received at least 1 dose of study drug. Here, 'Overall number of participants analyzed' signifies participants with a laboratory result.

Potentially clinically significant abnormal vital signs findings included: Pulse rate ≥120 beats per minute (bpm) and increase from baseline of ≥15 bpm, or ≤50 bpm and decrease from baseline of ≥15 bpm; Systolic blood pressure ≤90 millimeters of mercury (mmHg) and decrease from baseline of ≥20 mmHg, or ≥180 mmHg and increase from baseline of ≥20 mmHg; Diastolic blood pressure ≤50 mmHg and decrease from baseline of ≥15 mmHg, or ≥105 mmHg and increase from baseline of ≥15 mmHg; Temperature \>38.3 degrees celsius (°C). A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. Baseline refers to the baseline values from the pivotal studies.

Time frame: Baseline up to follow-up (Week 68)

Population: Safety analysis set included all participants who received at least 1 dose of study drug. Here, 'Overall number of participants analyzed' signifies participants with a vital sign result.

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. Baseline refers to the baseline values from the pivotal studies.

Time frame: Baseline up to end of treatment (Week 40)

Population: Safety analysis set included all participants who received at least 1 dose of study drug.

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. Baseline refers to the baseline values from the pivotal studies.

Time frame: Baseline up to follow-up (Week 68)

Population: Safety analysis set included all participants who received at least 1 dose of study drug.

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. Baseline refers to the baseline values from the pivotal studies.

Time frame: Baseline up to follow-up (Week 68)

Population: ITT analysis set included all participants who were enrolled in this study for long-term safety evaluation, regardless if they received study treatment or not.