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

Cluster Headache Clinical Trial

— ENFORCE  

Official title:

A Multicenter, Double-Blind, Double-Dummy Study to Explore the Long-Term Safety and Efficacy of TEV-48125 for the Prevention of Cluster Headache

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03107052
• Other study ID #: TV48125-CNS-30058
• Secondary ID: 2016-003172-43
• Status: Terminated
• Phase: Phase 3
• Start date: April 27, 2017
• Est. completion date: June 11, 2019

Study information

• Verified date: November 2021
• Source: Teva Branded Pharmaceutical Products R&D, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a 68-week study to evaluate the long-term safety and efficacy of fremanezumab in participants with cluster headache (CH). Participants who complete the pivotal studies TV48125-CNS-30056 (NCT02945046) and TV48125-CNS-30057 (NCT02964338) and enroll into the current study will visit the investigational center for investigational medicinal product (IMP) administration, safety and efficacy assessments, and blood and urine collections for pharmacokinetics, immunogenicity (anti-drug antibodies [ADAs]), and biomarker analyses. Participants will return to the investigational center for a follow-up visit to evaluate ADAs, fremanezumab concentrations, biomarkers, and safety (adverse events and concomitant medications) approximately 7.5 months after the last dose of IMP.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 275
• Est. completion date: June 11, 2019
• Est. primary completion date: June 11, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• The participant completes either the Phase 3 pivotal study for ECH (Study TV48125-CNS-30056) or the Phase 3 pivotal study for CCH (Study TV48125-CNS-30057) without important protocol deviations related to participant safety and participant compliance.
• Prior to 15 June 2018, participants from the ECH study and the CCH study were enrolled. After 15 June 2018, only participants who participated in the ECH study (Study TV48125-CNS-30056) will be enrolled for active treatment.
• In addition, participants who do not complete the pivotal efficacy studies, and participants who complete the pivotal efficacy studies but will not continue treatment during this long-term safety study, will be offered to enroll in this study for the purpose of evaluating ADAs, and safety (adverse events and concomitant medications) approximately 7.5 months after administration of the last dose of the IMP.
• Additional criteria apply, please contact the investigator for more information

Exclusion Criteria:

• Any finding that, in the judgment of the investigator, is a clinically significant abnormality, including serum chemistry, hematology, coagulation, and urinalysis test values (abnormal tests may be repeated for confirmation)
• Additional criteria apply, please contact the investigator for more information

Related Conditions & MeSH terms

• Cluster Headache
• Headache

Intervention

Drug:
• Fremanezumab
Fremanezumab

Locations

Country	Name	City	State
Australia	Teva Investigational Site 78120	Auchenflower
Australia	Teva Investigational Site 78118	Clayton
Australia	Teva Investigational Site 78123	Melbourne
Australia	Teva Investigational Site 78122	Parkville
Australia	Teva Investigational Site 78121	Randwick
Canada	Teva Investigational Site 11130	Calgary
Canada	Teva Investigational Site 11132	Newmarket	Ontario
Finland	Teva Investigational Site 40030	Helsinki
Finland	Teva Investigational Site 40031	Oulu
Finland	Teva Investigational Site 40029	Turku
Germany	Teva Investigational Site 32666	Berlin
Germany	Teva Investigational Site 32667	Bochum
Germany	Teva Investigational Site 32660	Essen
Germany	Teva Investigational Site 32665	Hamburg
Germany	Teva Investigational Site 32662	Kiel
Germany	Teva Investigational Site 32661	Konigstein im Taunus
Germany	Teva Investigational Site 32663	Rostock
Israel	Teva Investigational Site 80124	Ashkelon
Israel	Teva Investigational Site 80122	Hadera
Israel	Teva Investigational Site 80125	Holon
Israel	Teva Investigational Site 80121	Jerusalem
Israel	Teva Investigational Site 80123	Netanya
Israel	Teva Investigational Site 80120	Ramat Gan
Israel	Teva Investigational Site 80127	Tel Aviv
Israel	Teva Investigational Site 80126	Tel-Aviv
Italy	Teva Investigational Site 30190	Milan
Italy	Teva Investigational Site 30192	Modena
Italy	Teva Investigational Site 30194	Napoli
Italy	Teva Investigational Site 30193	Pavia
Italy	Teva Investigational Site 30189	Rome
Italy	Teva Investigational Site 30191	Rome
Netherlands	Teva Investigational Site 38118	Leiden
Netherlands	Teva Investigational Site 38119	Nijmegen
Netherlands	Teva Investigational Site 38117	Zwolle
Poland	Teva Investigational Site 53380	Bialystok
Poland	Teva Investigational Site 53379	Krakow
Poland	Teva Investigational Site 53383	Krakow
Poland	Teva Investigational Site 53382	Lodz
Poland	Teva Investigational Site 53381	Szczecin
Spain	Teva Investigational Site 31211	Galdakao.
Spain	Teva Investigational Site 31214	Madrid
Spain	Teva Investigational Site 31213	Sevilla
Spain	Teva Investigational Site 31212	Valladolid
Spain	Teva Investigational Site 31215	Zaragoza
Sweden	Teva Investigational Site 42047	Huddinge
Sweden	Teva Investigational Site 42045	Vallingby
United Kingdom	Teva Investigational Site 34224	Glasgow
United Kingdom	Teva Investigational Site 34222	Liverpool
United Kingdom	Teva Investigational Site 34220	London
United Kingdom	Teva Investigational Site 34223	London
United Kingdom	Teva Investigational Site 34221	Oxford
United States	Teva Investigational Site 13827	Albuquerque	New Mexico
United States	Teva Investigational Site 13816	Amherst	New York
United States	Teva Investigational Site 13818	Ann Arbor	Michigan
United States	Teva Investigational Site 13837	Aurora	Colorado
United States	Teva Investigational Site 13819	Canoga Park	California
United States	Teva Investigational Site 13826	Chicago	Illinois
United States	Teva Investigational Site 13825	Cleveland	Ohio
United States	Teva Investigational Site 13814	Colorado Springs	Colorado
United States	Teva Investigational Site 13833	Columbus	Georgia
United States	Teva Investigational Site 13836	Denver	Colorado
United States	Teva Investigational Site 13813	Englewood	Colorado
United States	Teva Investigational Site 13810	Gainesville	Florida
United States	Teva Investigational Site 13832	Las Vegas	Nevada
United States	Teva Investigational Site 13835	Las Vegas	Nevada
United States	Teva Investigational Site 13831	Lebanon	New Hampshire
United States	Teva Investigational Site 13821	New Haven	Connecticut
United States	Teva Investigational Site 13817	New York	New York
United States	Teva Investigational Site 13815	Orlando	Florida
United States	Teva Investigational Site 13829	Ormond Beach	Florida
United States	Teva Investigational Site 13824	Philadelphia	Pennsylvania
United States	Teva Investigational Site 13834	Phoenix	Arizona
United States	Teva Investigational Site 13820	Princeton	New Jersey
United States	Teva Investigational Site 13809	Raleigh	North Carolina
United States	Teva Investigational Site 13841	Richmond	Texas
United States	Teva Investigational Site 13830	Saint Petersburg	Florida
United States	Teva Investigational Site 13839	Salisbury	North Carolina
United States	Teva Investigational Site 13811	Santa Monica	California
United States	Teva Investigational Site 13812	Stamford	Connecticut
United States	Teva Investigational Site 13823	Stanford	California
United States	Teva Investigational Site 13840	Tampa	Florida
United States	Teva Investigational Site 13842	Tampa	Florida
United States	Teva Investigational Site 13822	Virginia Beach	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Teva Branded Pharmaceutical Products R&D, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Finland,  Germany,  Israel,  Italy,  Netherlands,  Poland,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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. Baseline refers to the baseline values from the pivotal studies.	Baseline up to follow-up (Week 68)
Primary	Number of Participants With Potentially Clinically Significant Abnormal Laboratory Results: Serum Chemistry	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.	Baseline up to end of treatment (Week 40)
Primary	Number of Participants With Potentially Clinically Significant Abnormal Laboratory Results: Hematology	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.	Baseline up to end of treatment (Week 40)
Primary	Number of Participants With Potentially Clinically Significant Abnormal Laboratory Results: Urinalysis	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.	Baseline up to end of treatment (Week 40)
Primary	Number of Participants With Shift From Baseline to Endpoint (Last Assessment) 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. Baseline refers to the baseline values from the pivotal studies.	Baseline up to end of treatment (Week 40)
Primary	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 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.	Baseline up to follow-up (Week 68)
Primary	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. Baseline refers to the baseline values from the pivotal studies.	Baseline up to follow-up (Week 68)
Primary	Number of Participants With Abnormal Physical Examination Findings	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.	Baseline up to follow-up (Week 68)
Primary	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, 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.	Baseline up to Week 36
Primary	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. Baseline refers to the baseline values from the pivotal studies.	Baseline up to Week 36
Primary	Number of Participants Who Received Concomitant Medications	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.	Baseline up to follow-up (Week 68)
Primary	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. Baseline refers to the baseline values from the pivotal studies.	Baseline up to follow-up (Week 68)