Chronic Cluster Headache Clinical Trial
Official title:
A Multicenter, Randomized, Double-Blind, Double-Dummy, Placebo-Controlled, Parallel-Group Study Comparing the Efficacy and Safety of 2 Dose Regimens (Intravenous/Subcutaneous and Subcutaneous) of TEV-48125 Versus Placebo for the Prevention of Chronic Cluster Headache
Verified date | November 2021 |
Source | Teva Branded Pharmaceutical Products R&D, Inc. |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
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. |
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 |
Lead Sponsor | Collaborator |
---|---|
Teva Branded Pharmaceutical Products R&D, Inc. |
United States, Australia, Canada, Finland, Germany, Israel, Italy, Netherlands, Poland, Spain, Sweden, United Kingdom,
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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