NCT02945046 is a Phase 3 clinical trial of Fremanezumab in Episodic Cluster Headache, sponsored by Teva Branded Pharmaceutical Products R&D, Inc..

Who is sponsoring NCT02945046?

NCT02945046 is sponsored by Teva Branded Pharmaceutical Products R&D, Inc..

What drugs are being tested in NCT02945046?

Interventions in NCT02945046: Fremanezumab, Placebo.

What condition does NCT02945046 study?

NCT02945046 studies Episodic Cluster Headache.

Is NCT02945046 still recruiting?

NCT02945046 is currently terminated. Last updated 9 November 2021.

Are results published for NCT02945046?

Yes — primary outcome results have been posted to ClinicalTrials.gov. See the outcomes section above for details.

Last reviewed 2021-11-09 · How we verify

NCT02945046

Name: Drug Landscape Pharmaceutical Database
Creator: Drug Landscape
Published: 2026-01-01
License: https://creativecommons.org/licenses/by/4.0/

A Study to Evaluate the Efficacy and Safety of TEV-48125 (Fremanezumab) for the Prevention of Episodic Cluster Headache (ECH)

Terminated Phase 3 Results posted Last updated 9 November 2021

What this trial tests

Phase 3 trial testing Fremanezumab in Episodic Cluster Headache in 169 participants. Terminated before completion.

Timeline

19 January 2017

Primary endpoint
13 May 2019

13 May 2019

Quick facts

Lead sponsor	Teva Branded Pharmaceutical Products R&D, Inc.
Phase	Phase 3
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	169
Start date	19 January 2017
Primary completion	13 May 2019
Estimated completion	13 May 2019
Sites	82 locations across Italy, Finland, Netherlands, Sweden, United Kingdom, Germany, Israel, Poland

Drugs / interventions tested

Fremanezumab (FREMANEZUMAB) — full drug profile →
Placebo

Conditions studied

Episodic Cluster Headache — all drugs for Episodic Cluster Headache →

Sponsor

Teva Branded Pharmaceutical Products R&D, Inc. — full company profile →

Who can join

Adults 18 to 70, any sex, with Episodic Cluster Headache. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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 Primary · 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 wi

Group	Value	95% CI
Placebo	-5.7	± 1.00
Fremanezumab 675 mg/Placebo/Placebo	-5.8	± 1.02
Fremanezumab 900/225/225 mg	-7.6	± 1.01

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 Secondary · Baseline (Week 0), up to Week 4

Group	Value	95% CI
Placebo	60
Fremanezumab 675 mg/Placebo/Placebo	55
Fremanezumab 900/225/225 mg	75

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 Secondary · 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 p

Group	Value	95% CI
Placebo	-8.4	± 0.66
Fremanezumab 675 mg/Placebo/Placebo	-8.9	± 0.68
Fremanezumab 900/225/225 mg	-9.6	± 0.67

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 Secondary · 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)

Group	Value	95% CI
Placebo	-10.8	± 0.75
Fremanezumab 675 mg/Placebo/Placebo	-10.8	± 0.78
Fremanezumab 900/225/225 mg	-10.9	± 0.78

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 Secondary · 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 he

Group	Value	95% CI
Placebo	-1.6	± 0.36
Fremanezumab 675 mg/Placebo/Placebo	-2.4	± 0.36
Fremanezumab 900/225/225 mg	-2.8	± 0.36

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 Secondary · 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.

Group	Value	95% CI
Placebo	-1.1	± 0.30
Fremanezumab 675 mg/Placebo/Placebo	-1.5	± 0.31
Fremanezumab 900/225/225 mg	-1.0	± 0.30

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 Secondary · 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 vis

Baseline

Group	Value	95% CI
Placebo	10
Fremanezumab 675 mg/Placebo/Placebo	14
Fremanezumab 900/225/225 mg	7
Placebo	3
Fremanezumab 675 mg/Placebo/Placebo	5
Fremanezumab 900/225/225 mg	8
Placebo	3
Fremanezumab 675 mg/Placebo/Placebo	3
Fremanezumab 900/225/225 mg	3
Placebo	37
Fremanezumab 675 mg/Placebo/Placebo	31
Fremanezumab 900/225/225 mg	28

Week 1

Group	Value	95% CI
Placebo	2
Fremanezumab 675 mg/Placebo/Placebo	4
Fremanezumab 900/225/225 mg	1
Placebo	2
Fremanezumab 675 mg/Placebo/Placebo	2
Fremanezumab 900/225/225 mg	1
Placebo	5
Fremanezumab 675 mg/Placebo/Placebo	3
Fremanezumab 900/225/225 mg	2
Placebo	19
Fremanezumab 675 mg/Placebo/Placebo	11
Fremanezumab 900/225/225 mg	9

Week 4

Group	Value	95% CI
Placebo	1
Fremanezumab 675 mg/Placebo/Placebo	1
Fremanezumab 900/225/225 mg	2
Placebo	3
Fremanezumab 675 mg/Placebo/Placebo	0
Fremanezumab 900/225/225 mg	1
Placebo	4
Fremanezumab 675 mg/Placebo/Placebo	2
Fremanezumab 900/225/225 mg	0
Placebo	8
Fremanezumab 675 mg/Placebo/Placebo	11
Fremanezumab 900/225/225 mg	5

Week 8

Group	Value	95% CI
Placebo	1
Fremanezumab 675 mg/Placebo/Placebo	1
Fremanezumab 900/225/225 mg	0
Placebo	3
Fremanezumab 675 mg/Placebo/Placebo	0
Fremanezumab 900/225/225 mg	1
Placebo	0
Fremanezumab 675 mg/Placebo/Placebo	1
Fremanezumab 900/225/225 mg	1
Placebo	13
Fremanezumab 675 mg/Placebo/Placebo	8
Fremanezumab 900/225/225 mg	12

Week 12

Group	Value	95% CI
Placebo	3
Fremanezumab 675 mg/Placebo/Placebo	2
Fremanezumab 900/225/225 mg	2
Placebo	0
Fremanezumab 675 mg/Placebo/Placebo	0
Fremanezumab 900/225/225 mg	1
Placebo	2
Fremanezumab 675 mg/Placebo/Placebo	1
Fremanezumab 900/225/225 mg	0
Placebo	16
Fremanezumab 675 mg/Placebo/Placebo	16
Fremanezumab 900/225/225 mg	16

Number of Participants With Adverse Events (AEs) Secondary · 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 th

Any AEs

Group	Value	95% CI
Placebo	28
Fremanezumab 675 mg/Placebo/Placebo	26
Fremanezumab 900/225/225 mg	28

Treatment-related AEs

Group	Value	95% CI
Placebo	8
Fremanezumab 675 mg/Placebo/Placebo	11
Fremanezumab 900/225/225 mg	13

Serious AEs

Group	Value	95% CI
Placebo	5
Fremanezumab 675 mg/Placebo/Placebo	0
Fremanezumab 900/225/225 mg	1

AEs leading to discontinuation

Group	Value	95% CI
Placebo	1
Fremanezumab 675 mg/Placebo/Placebo	0
Fremanezumab 900/225/225 mg	2

Number of Participants With Potentially Clinically Significant Laboratory (Serum Chemistry, Hematology, and Urinalysis) Abnormal Results Secondary · 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

With at least 1 serum chemistry abnormality

Group	Value	95% CI
Placebo	1
Fremanezumab 675 mg/Placebo/Placebo	1
Fremanezumab 900/225/225 mg	0

With at least 1 hematology abnormality

Group	Value	95% CI
Placebo	4
Fremanezumab 675 mg/Placebo/Placebo	1
Fremanezumab 900/225/225 mg	4

With at least 1 urinalysis abnormality

Group	Value	95% CI
Placebo	0
Fremanezumab 675 mg/Placebo/Placebo	0
Fremanezumab 900/225/225 mg	0

Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results Secondary · 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.

Group	Value	95% CI
Placebo	0
Fremanezumab 675 mg/Placebo/Placebo	0
Fremanezumab 900/225/225 mg	0
Placebo	0
Fremanezumab 675 mg/Placebo/Placebo	0
Fremanezumab 900/225/225 mg	0
Placebo	0
Fremanezumab 675 mg/Placebo/Placebo	0
Fremanezumab 900/225/225 mg	0
Placebo	0
Fremanezumab 675 mg/Placebo/Placebo	0
Fremanezumab 900/225/225 mg	0

Prothrombin INR

Group	Value	95% CI
Placebo	0
Fremanezumab 675 mg/Placebo/Placebo	0
Fremanezumab 900/225/225 mg	0
Placebo	0
Fremanezumab 675 mg/Placebo/Placebo	0
Fremanezumab 900/225/225 mg	0
Placebo	0
Fremanezumab 675 mg/Placebo/Placebo	0
Fremanezumab 900/225/225 mg	0
Placebo	0
Fremanezumab 675 mg/Placebo/Placebo	0
Fremanezumab 900/225/225 mg	0

Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values Secondary · 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.

Group	Value	95% CI
Placebo	3
Fremanezumab 675 mg/Placebo/Placebo	0
Fremanezumab 900/225/225 mg	1

Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters Secondary · 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.

Group	Value	95% CI
Placebo	35
Fremanezumab 675 mg/Placebo/Placebo	33
Fremanezumab 900/225/225 mg	23
Placebo	6
Fremanezumab 675 mg/Placebo/Placebo	1
Fremanezumab 900/225/225 mg	5
Placebo	0
Fremanezumab 675 mg/Placebo/Placebo	0
Fremanezumab 900/225/225 mg	0
Placebo	4
Fremanezumab 675 mg/Placebo/Placebo	9
Fremanezumab 900/225/225 mg	4

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline up to Week 12. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo

Serious: 5/59 (8%)

Deaths: 0/59

Fremanezumab 675 mg/Placebo/Placebo

Serious: 0/55 (0%)

Deaths: 0/55

Fremanezumab 900/225/225 mg

Serious: 1/55 (2%)

Deaths: 0/55

Serious adverse events (6 terms)

Reaction	System	Placebo	Fremanezumab 675 mg/Placeb…	Fremanezumab 900/225/225 mg
Cluster headache	Nervous system disorders	—	—	—
Vertigo	Ear and labyrinth disorders	—	—	—
Duodenitis	Gastrointestinal disorders	—	—	—
Chest pain	General disorders	—	—	—
Lumbar vertebral fracture	Injury, poisoning and procedural complications	—	—	—
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—

Other adverse events (4 terms — click to expand)

Reaction	System	Placebo	Fremanezumab 675 mg/Placeb…	Fremanezumab 900/225/225 mg
Injection site induration	General disorders	—	—	—
Injection site pain	General disorders	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—
Influenza	Infections and infestations	—	—	—

Most-reported serious reactions: Cluster headache, Vertigo, Duodenitis, Chest pain, Lumbar vertebral fracture, Breast cancer.

Data from ClinicalTrials.gov NCT02945046 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

CGRP and the Trigeminal System in Migraine.
Iyengar S, Johnson KW, Ossipov MH, Aurora SK. · · 2019 · cited 309× · PMID 30982963 · DOI 10.1111/head.13529
Antibodies to watch in 2017.
Reichert JM. · · 2017 · cited 194× · PMID 27960628 · DOI 10.1080/19420862.2016.1269580
New Trends in Migraine Pharmacology: Targeting Calcitonin Gene-Related Peptide (CGRP) With Monoclonal Antibodies.
Scuteri D, Adornetto A, Rombolà L, Naturale MD, et al · · 2019 · cited 63× · PMID 31024319 · DOI 10.3389/fphar.2019.00363
Fremanezumab: First Global Approval.
Hoy SM. · · 2018 · cited 35× · PMID 30406901 · DOI 10.1007/s40265-018-1004-5
Debate: Are cluster headache and migraine distinct headache disorders?
Al-Karagholi MA, Peng KP, Petersen AS, De Boer I, et al · · 2022 · cited 18× · PMID 36447146 · DOI 10.1186/s10194-022-01504-x
Challenges and complexities in designing cluster headache prevention clinical trials: A narrative review.
Dodick DW, Goadsby PJ, Ashina M, Tassorelli C, et al · · 2022 · cited 17× · PMID 35363381 · DOI 10.1111/head.14292
Treatment of Cluster Headache.
Kingston WS, Dodick DW. · · 2018 · cited 11× · PMID 29720813 · DOI 10.4103/aian.aian_17_18
Cranial autonomic symptoms and response to monoclonal antibodies targeting the Calcitonin gene-related peptide pathway: A real-world study.
De Matteis E, Caponnetto V, Casalena A, Frattale I, et al · · 2022 · cited 6× · PMID 36212640 · DOI 10.3389/fneur.2022.973226

Verify or expand the search:

Other trials of Fremanezumab

Trials testing the same drug.

NCT07029126 — Improving the Perception of Stress and Mutuality in Caregivers (MI-DEAR Study) of Migraine Patients With Depressive Symp · recruiting
NCT06659120 — Fremanezumab for the Prevention of Menstrually-related Migraine Attacks · recruiting
NCT05281770 — Monoclonal CGRP Antibodies for Migraine Prevention - a Nationwide Real Life Study · unknown
NCT05458011 — A Randomized, Double-Blind, Placebo-Controlled Study With an Open-Label Period on Efficacy and Safety of Fremanezumab in · Phase 3 · completed
NCT05284019 — Real World Effectiveness of Eptinezumab in Participants With Migraine · Phase 4 · terminated

Other Teva Branded Pharmaceutical Products R&D, Inc. trials

Trials by the same sponsor.

NCT06664619 — A Randomized, Double-Blind, Placebo-Controlled Trial on Efficacy and Safety of Fluticasone Propionate/Albuterol Sulfate · Phase 3 · recruiting
NCT06627231 — Mass Balance Clinical Trial With TEV-56286 · Phase 1 · completed
NCT06480552 — An Open-label Dose Escalation/Expansion Trial to Evaluate the Safety and Anti-tumor Activity of TEV-56278 Alone or in Co · Phase 1 · recruiting
NCT06290102 — Pharmacokinetic Profile and Safety of Fluticasone Propionate and Albuterol Sulfate in Combination When Compared to Fluti · Phase 1 · completed
NCT06253546 — Safety, Tolerability, and Pharmacokinetic Study of TV-44749 in Chinese Patients With Schizophrenia · Phase 1 · completed

Verify against primary sources

ClinicalTrials.gov — authoritative US registry record
WHO ICTRP — international registry index
EU Clinical Trials Register
Sponsor press releases (Google)

Data sources for this page

Trial protocol + status: ClinicalTrials.gov NCT02945046 (US National Library of Medicine, public domain)
Publications: Europe PMC API search by NCT ID, retrieved 10 June 2026
Drug + disease cross-links: matched in real time against Drug Landscape's normalised drug + company + condition tables
Sponsor: as reported to ClinicalTrials.gov by Teva Branded Pharmaceutical Products R&D, Inc.
Last refreshed: 9 November 2021

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02945046.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing