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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT02964338
Other study ID # TV48125-CNS-30057
Secondary ID 2016-003171-21
Status Terminated
Phase Phase 3
First received
Last updated
Start date January 17, 2017
Est. completion date July 18, 2018

Study information

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

Clinical Trial Summary

The purpose of the current study is to evaluate the efficacy and safety of Fremanezumab (TEV-48125), in the prevention of CCH in adult participants.


Recruitment information / eligibility

Status Terminated
Enrollment 259
Est. completion date July 18, 2018
Est. primary completion date July 18, 2018
Accepts healthy volunteers No
Gender All
Age group 18 Years to 70 Years
Eligibility Inclusion Criteria: - The participant has a history of CCH according to the International Classification of Headache Disorders - 3 beta criteria (Headache Classification Committee of the International Headache Society [IHS] 2013) for greater than or equal to (=)12 months prior to screening. - The participant has a total body weight of =45 kilograms (kg) (99 pounds [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. - If a participant is receiving Botox, it should be in a stable dose regimen, which is 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 (12 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 cluster headache (CH) cycle within less than or equal to (=)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 investigational medicinal product (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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Fremanezumab
Fremanezumab will be administered as per the dose and schedule specified in the respective arms.
Placebo
Placebo matching to fremanezumab will be administered as per the schedule specified in the respective arms.

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
Canada Teva Investigational Site 11131 Toronto
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 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 34222 Augusta Georgia
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 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 Mean Change From Baseline in the Overall Monthly Average Number of CH Attacks 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. 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 monthly 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. Baseline Period (from at least Week -4 to Week 0), Up to Week 12
Secondary Percentage of Participants With a =50% Reduction From Baseline in the Monthly Average Number of CH Attacks 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. Baseline Period (from at least Week -4 to Week 0) up to Week 12
Secondary Mean Change From Baseline in the Monthly Average Number of CH Attacks at Week 4 and 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) =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. Mean change from baseline in monthly average number of CH attacks during 4-week period after administration of first dose of study drug (based on Week 0 to 4 data) and during 4-week period after administration of third dose of study drug (based on Week 8 to 12 data) is reported. Baseline Period (from at least Week -4 to Week 0), Week 4 and Week 12
Secondary Mean Change From Baseline in the Overall Weekly Average Number of Days With Use of Cluster-Specific Acute Headache Medications (Triptans and Ergot Compounds) 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. 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. Baseline Period (from at least Week -4 to Week 0), Up to Week 12
Secondary Mean Change From Baseline in the Weekly Average Number of Days Oxygen Was Used to Treat CCH Up to Week 12 Baseline data and the mean change from baseline in the overall weekly average number of days oxygen was used to treat CCH during the 12-week period after administration of the first dose of study drug (based on Week 0 to 12 data) is reported. Baseline Period (from at least Week -4 to Week 0), Up to Week 12
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. Baseline and Weeks 1, 4, 8, and 12
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. Severity was rated by the Investigator on a scale of mild, moderate and severe, with severe as an AE that prevents usual activities. 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 up to Week 12
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 (units/liter [U/L]) =3*upper limit of normal (ULN); Aspartate Aminotransferase (U/L) =3*ULN; Bilirubin (Total) =34.2 micromole/liter (umol/L); Blood Urea Nitrogen =10.71 millimole (mmol)/L; Creatinine =177 umol/L; Gamma Glutamyl Transferase (U/L) =3*ULN; hemoglobin less than (<)115 grams (g)/L (males) or less than or equal to (=)95 g/L (females); leukocytes =20*10^9/L or =3*10^9/L; Eosinophils/Leukocytes =10%; Hematocrit <0.37 L/L (males) and <0.32 L/L (females); platelets =700*10^9/L or =75*10^9/L; blood =2 unit increase from baseline; urine glucose (milligrams/decilitre [mg/dL]) =2 U increase from baseline; ketones (mg/dL) =2 U increase from baseline; urine protein (mg/dL) =2 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 up to Week 12
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. Baseline up to Week 12
Secondary Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values Potentially clinically significant abnormal vital signs findings included: pulse rate =50 beats/minute (bpm) and decrease of =15 bpm, or =120 bpm and increase of =15 bpm; systolic blood pressure =90 millimeters of mercury (mmHg) and decrease of =20 mmHg, or =180 mmHg and increase of =20 mmHg; diastolic blood pressure =50 mmHg and decrease of =15 mmHg, or =105 mmHg and increase of =15 mmHg; respiratory rate <10 breaths/minute; and body temperature =38.3 degrees centigrade and change of =1.1 degrees centigrade. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. Baseline up to Week 12
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. Baseline to Week 12
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, bruising, hypersensitivity, swelling, rash, and flushing. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. Baseline up to Week 12
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. Baseline up to Week 12
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