Clinical Trial Results:
A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study Comparing the Efficacy, Safety, and Tolerability of Subcutaneous Administration of Fremanezumab Versus Placebo for the Preventive Treatment of Episodic Migraine in Pediatric Patients 6 to 17 Years of Age
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Summary
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EudraCT number |
2019-002055-42 |
Trial protocol |
DE FI PL NL IT |
Global end of trial date |
13 Mar 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
26 Sep 2024
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First version publication date |
26 Sep 2024
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
TV48125-CNS-30083
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04458857 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Teva Branded Pharmaceutical Products R&D, Inc.
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Sponsor organisation address |
145 Brandywine Parkway, West Chester, United States, 19380
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Public contact |
Director, Clinical Research, Teva Branded Pharmaceutical Products, R&D Inc., MedInfo@tevaeu.com
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Scientific contact |
Director, Clinical Research, Teva Branded Pharmaceutical Products, R&D Inc., MedInfo@tevaeu.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-001877-PIP01-15 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
18 Apr 2024
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
13 Mar 2024
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Global end of trial reached? |
Yes
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Global end of trial date |
13 Mar 2024
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of the study was to evaluate the efficacy of fremanezumab as compared to placebo for the preventive treatment of episodic migraine (EM).
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Protection of trial subjects |
This trial was conducted in full accordance with the International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) Consolidated Guideline (E6) and ISO 14155: Clinical investigation of medical devices for human subjects – Good clinical practice and any applicable national and local laws and regulations.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
15 Jul 2020
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Germany: 11
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Country: Number of subjects enrolled |
Spain: 7
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Country: Number of subjects enrolled |
Canada: 10
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Country: Number of subjects enrolled |
Finland: 36
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Country: Number of subjects enrolled |
Israel: 20
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Country: Number of subjects enrolled |
Italy: 23
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Country: Number of subjects enrolled |
Netherlands: 2
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Country: Number of subjects enrolled |
Poland: 56
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Country: Number of subjects enrolled |
United States: 70
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Worldwide total number of subjects |
235
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EEA total number of subjects |
135
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
64
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Adolescents (12-17 years) |
171
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
A total of 411 participants were screened; of which 235 participants were randomized and included in the analysis. | ||||||||||||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Carer, Assessor | ||||||||||||||||||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo | ||||||||||||||||||||||||||||||||||||||||
Arm description |
Participants received placebo matched to fremanezumab subcutaneously (SC) for 3 months (Days 1, 29, and 57). | ||||||||||||||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Placebo matched to fremanezumab was administered per schedule specified in the arm description.
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Arm title
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Fremanezumab Dose A | ||||||||||||||||||||||||||||||||||||||||
Arm description |
Participants weighing <threshold weight received fremanezumab SC at dose A for 3 months (Days 1, 29, and 57). | ||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Fremanezumab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Fremanezumab was administered per schedule specified in the arm description.
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Arm title
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Fremanezumab Dose B | ||||||||||||||||||||||||||||||||||||||||
Arm description |
Participants weighing ≥threshold weight received fremanezumab SC at dose B for 3 months (Days 1, 29, and 57). | ||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Fremanezumab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Fremanezumab was administered per schedule specified in the arm description.
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Baseline characteristics reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Participants received placebo matched to fremanezumab subcutaneously (SC) for 3 months (Days 1, 29, and 57). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Fremanezumab Dose A
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Reporting group description |
Participants weighing <threshold weight received fremanezumab SC at dose A for 3 months (Days 1, 29, and 57). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Fremanezumab Dose B
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Reporting group description |
Participants weighing ≥threshold weight received fremanezumab SC at dose B for 3 months (Days 1, 29, and 57). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Participants received placebo matched to fremanezumab subcutaneously (SC) for 3 months (Days 1, 29, and 57). | ||
Reporting group title |
Fremanezumab Dose A
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Reporting group description |
Participants weighing <threshold weight received fremanezumab SC at dose A for 3 months (Days 1, 29, and 57). | ||
Reporting group title |
Fremanezumab Dose B
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Reporting group description |
Participants weighing ≥threshold weight received fremanezumab SC at dose B for 3 months (Days 1, 29, and 57). | ||
Subject analysis set title |
Fremanezumab
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Participants received fremanezumab SC for 3 months (Days 1, 29, and 57).
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End point title |
Mean Change From Baseline in Monthly Average Number of Migraine Days During 12-Week Period After the First Dose of Study Drug [1] | ||||||||||||
End point description |
A migraine day was defined as a calendar day where a participant reported either of the following: A calendar day (0:00 to 23:59) demonstrating at least 2 consecutive hours of a headache that was accompanied by ≥1 migraine symptom(s) or a calendar day demonstrating a headache of any duration that was treated with migraine specific medications (NSAIDs, paracetamol or triptans and ergot compounds). Monthly averages were derived and normalized to 28 days equivalent by formula: (number of days of efficacy variable over 12-week period/number of days with assessments recorded in e-diary for 12-week period) * 28. Least square (LS) mean was calculated using analysis of covariance (ANCOVA). Full analysis set (FAS): all randomized participants who received at least 1 dose of study drug and had at least 10 days of diary entries postbaseline for efficacy assessments on primary endpoint. Efficacy analysis was planned to be evaluated combined for both fremanezumab dose treatment groups.
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End point type |
Primary
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End point timeframe |
Baseline (Day -28 to Day -1), up to Week 12
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| Notes [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Efficacy analysis was planned to be evaluated combined for fremanezumab low and high dose treatment groups. |
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Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Comparison groups |
Placebo v Fremanezumab
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Number of subjects included in analysis |
234
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.021 | ||||||||||||
Method |
ANCOVA | ||||||||||||
Parameter type |
LS mean Difference | ||||||||||||
Point estimate |
-1
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-1.9 | ||||||||||||
upper limit |
-0.16 | ||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.44
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End point title |
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | ||||||||||||
End point description |
An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious AEs (SAEs) were defined as death, a life-threatening AE, 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 participant and required medical intervention to prevent 1 of the outcomes listed in this definition. AEs were considered TEAEs if onset occurred on or after the first dose date. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. The safety analysis set included all randomized participants who received at least 1 dose of study drug.
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End point type |
Secondary
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End point timeframe |
Baseline up to Month 3
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of Participants With Shift From Baseline to Last Assessment in Electrocardiogram (ECG) Findings (Assessed by Investigator) | ||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The number of participants with a shift from Baseline (Normal, Abnormal CS [Clinically Significant], or Abnormal NCS [Not Clinically Significant]) in any of the following ECG parameters is reported by treatment group: Heart rate, PR interval, QRS interval, RR interval, QT interval, QT interval corrected using the Bazett's formula (QTcB), and QT interval corrected using the Fridericia formula (QTcF). Last assessment was defined as the last observed postbaseline interpretation. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. The safety analysis set included all randomized participants who received at least 1 dose of study drug.
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End point type |
Secondary
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End point timeframe |
Baseline to last assessment (up to Month 3)
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Number of Participants With Shift From Baseline to Last Assessment in ECG Findings (Assessed by Cardiologist) | ||||||||||||||||||||||||||||||||
End point description |
The number of participants with a shift from Baseline (Normal or Abnormal) in any of the following ECG parameters is reported by treatment group: Heart rate, PR interval, QRS interval, RR interval, QT interval, QTcB, and QTcF. Last assessment was defined as the last observed postbaseline interpretation. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. The safety analysis set included all randomized participants who received at least 1 dose of study drug.
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End point type |
Secondary
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End point timeframe |
Baseline to last assessment (up to Month 3)
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||
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End point title |
Number of Participants With One or More Potentially Clinically Significant Vital Signs Abnormalities | ||||||||||||
End point description |
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 ≤85 millimeters of mercury (mmHg) and decrease from baseline of ≥20 mmHg; Diastolic blood pressure ≥100 mmHg and increase from baseline of ≥15 mmHg; Respiratory rate <15 breaths/minute. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here, 'Overall number of participants analyzed' = participants with at least one Baseline and post-baseline vital sign assessment.
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End point type |
Secondary
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End point timeframe |
Baseline up to Month 3
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of Participants With Potentially Clinically Significant Abnormal Laboratory (Serum Chemistry, Hematology, Coagulation, and Urinalysis) Results | ||||||||||||||||||||||||||||
End point description |
Potentially clinically significant abnormal findings included- Serum chemistry tests: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) both ≥2*upper limit of normal (ULN); and bilirubin ≥34.2 micromole/liter (umol/L). Hematology tests: hemoglobin ≤100 grams (g)/L, leukocytes ≤3*10^9 cells/L, neutrophils ≤1*10^9 cells/L, eosinophils/leukocytes ≥10%, and platelets ≥700*10^9 cells/L or ≤75*10^9 cells/L. Coagulation parameter test: prothrombin international normalized ratio (INR) >1.5. Urinalysis laboratory tests: urine protein ≥2 units (U) increase from baseline. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here, 'Overall number of participants analyzed' and 'n'= participants with at least one Baseline and post-baseline assessment of the specified laboratory parameters.
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End point type |
Secondary
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End point timeframe |
Baseline up to Month 3
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||
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End point title |
Number of Participants With Abnormal Physical Examination Findings as Identified by the Investigator | ||||||||||||||||||||||||||||||||||||
End point description |
A complete physical examination included the following organ systems: general appearance; head, eyes, ears, nose, and throat (HEENT); chest and lungs; heart; abdomen; musculoskeletal; skin; lymph nodes; and neurological. Only the organ systems with abnormal physical findings in at least one treatment group have been reported. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. The safety analysis set included all randomized participants who received at least 1 dose of study drug. Here, 'Overall number of participants analyzed' = participants with at least one Baseline and post-baseline physical examination.
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End point type |
Secondary
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End point timeframe |
Baseline up to Month 3
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||
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End point title |
Number of Participants With Suicidal Ideation or Suicidal Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | ||||||||||||||||||||
End point description |
C-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. The ITT analysis set included all randomized participants. Here, 'Overall number of participants analyzed' = participants with both Baseline and Month 3 assessment.
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End point type |
Secondary
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End point timeframe |
Baseline and Month 3
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Mean Change From Baseline in Monthly Average Number of Headache Days of at Least Moderate Severity During 12-Week Period After the First Dose of Study Drug [2] | ||||||||||||
End point description |
A headache day of at least moderate severity was defined as a calendar day (00:00 to 23:59) where the participant reported either of the following: A day with headache pain that lasted ≥2 hours with a peak severity of at least moderate severity or a day where the participant used acute medication (triptans, ergots, NSAIDs or paracetamol) to treat a headache of any severity or duration. Monthly averages were derived and normalized to 28 days equivalent by formula: (number of days of efficacy variable over 12-week period/number of days with assessments recorded in e-diary for 12-week period) * 28. LS mean was calculated using ANCOVA. The FAS included all randomized participants who received at least 1 dose of study drug and had at least 10 days of diary entries postbaseline for efficacy assessments on the primary endpoint. Efficacy analysis was planned to be evaluated combined for both fremanezumab dose treatment groups.
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End point type |
Secondary
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End point timeframe |
Baseline (Day -28 to Day -1), up to Week 12
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| Notes [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Efficacy analysis was planned to be evaluated combined for fremanezumab low and high dose treatment groups. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of Participants Reaching at Least 50% Reduction in the Monthly Average Number of Migraine Days during the 12-week Period After the First Dose of Study Drug [3] | |||||||||
End point description |
A migraine day was defined as a calendar day where the participant reported either of the following: A calendar day (0:00 to 23:59) demonstrating at least 2 consecutive hours of a headache that was accompanied by ≥1 migraine symptom(s) or a calendar day (0:00 to 23:59) demonstrating a headache of any duration that was treated with migraine specific medications (NSAIDs, paracetamol or triptans and ergot compounds). Monthly averages were derived and normalized to 28 days equivalent by formula: (number of days of efficacy variable over 12-week period/number of days with assessments recorded in e-diary for 12-week period) * 28. The FAS included all randomized participants who received at least 1 dose of study drug and had at least 10 days of diary entries postbaseline for efficacy assessments on the primary endpoint. Efficacy analysis was planned to be evaluated combined for both fremanezumab dose treatment groups.
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End point type |
Secondary
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End point timeframe |
Baseline (Day -28 to Day -1) up to Week 12
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| Notes [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Efficacy analysis was planned to be evaluated combined for fremanezumab low and high dose treatment groups. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Mean Change From Baseline in Migraine-related Disability Score at Week 12, as Measured by the Pediatric Migraine Disability Assessment (PedMIDAS) Questionnaire [4] | ||||||||||||
End point description |
PedMIDAS questionnaire is a 6-item instrument developed to assess headache-related disability. It has been validated in participants aged 4 through 18 years and includes questions related to the impact of headache on school performance, disability at home (for example, inability to do chores or homework), and social/sport functioning. Total score: that is, the sum of 6 questions, was used for grading of disability, with scores of 0 to 10, 11 to 30, 31 to 50, and >50 interpreted as disability grades 1 (little or no disability), 2 (mild disability), 3 (moderate disability), and 4 (severe disability), respectively. Higher scores indicated severe disability. LS mean was calculated using ANCOVA. FAS included all randomized participants who received at least 1 dose of study drug and had at least 10 days of diary entries postbaseline for efficacy assessments on the primary endpoint. Efficacy analysis was planned to be evaluated combined for both fremanezumab dose treatment groups.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 12
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| Notes [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Efficacy analysis was planned to be evaluated combined for fremanezumab low and high dose treatment groups. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Mean Change From Baseline in Monthly Average Number of Days of Use of Any Acute Headache Medications During 12-Week Period After the First Dose of Study Drug [5] | ||||||||||||
End point description |
Participants recorded any headache medications (name of drug, number of tablets/capsules, and the dose in milligrams per tablet/capsule) taken each day in their electronic headache diary device. Acute headache medication included triptans and ergot compounds, NSAIDs or paracetamol. Monthly averages were derived and normalized to 28 days equivalent by formula: (number of days of efficacy variable over 12-week period/number of days with assessments recorded in e-diary for 12-week period) * 28. LS mean was calculated using ANCOVA. The FAS included all randomized participants who received at least 1 dose of study drug and had at least 10 days of diary entries postbaseline for efficacy assessments on the primary endpoint. Efficacy analysis was planned to be evaluated combined for both fremanezumab dose treatment groups.
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End point type |
Secondary
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End point timeframe |
Baseline (Day -28 to Day -1), up to Week 12
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| Notes [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Efficacy analysis was planned to be evaluated combined for fremanezumab low and high dose treatment groups. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Mean Change From Baseline in Quality of Life at Week 12, as Measured by Pediatric Quality of Life Inventory (PedsQL) Questionnaire [6] | ||||||||||||||||||||||||||||||
End point description |
PedsQL 4.0 (23-item health-related quality of life [QoL]) evaluates QoL in 4 areas: physical, emotional, social, and school functioning. For child and adolescent (8-18 years) and parent, a 5-point Likert scale was used to rate item severity (0=never a problem;1=almost never a problem; 2=sometimes a problem; 3=often a problem; 4=almost always a problem). For younger children (5-7 years), a 3-point Likert scale, anchored with a happy and a sad face, was used (0=not at all a problem; 2=sometimes a problem; 4=a lot of a problem). PedsQL yields a total QoL score and 2 summary scores: Physical Health Summary Score and Psychosocial Health Summary Score. To obtain scores, items were reverse scored, transformed to a 0 to 100 scale (0=100, 1=75, 2=50, 3=25, 4=0), and averaged; total scores near 0 indicated lower QoL, while scores approaching 100 indicated higher QoL. Analysis population: FAS. Efficacy analysis was planned to be evaluated combined for both fremanezumab dose groups.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 12
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| Notes [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Efficacy analysis was planned to be evaluated combined for fremanezumab low and high dose treatment groups. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
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End point title |
Number of Participants Developing Anti-drug Antibodies (ADAs) Throughout the Study [7] | |||||||||
End point description |
Number of participants who developed ADAs were reported. The FAS included all randomized participants who received at least 1 dose of study drug and had at least 10 days of diary entries postbaseline for efficacy assessments on the primary endpoint. Here, 'Overall number of participants analyzed' = Participants who had Baseline and at least 1 postbaseline ADA assessment.
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End point type |
Secondary
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End point timeframe |
Baseline up to Month 3
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| Notes [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The end point is reporting statistics for the specified arms only. |
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| No statistical analyses for this end point | ||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Baseline up to Month 3
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Adverse event reporting additional description |
The safety analysis set included all randomized participants who received at least 1 dose of study drug.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
26.0
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Reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Participants received placebo matched to fremanezumab SC for 3 months (Days 1, 29, and 57). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Fremanezumab Dose B
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Reporting group description |
Participants weighing ≥threshold weight received fremanezumab SC at dose B for 3 months (Days 1, 29, and 57). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Fremanezumab Dose A
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Reporting group description |
Participants weighing <threshold weight received fremanezumab SC at dose A for 3 months (Days 1, 29, and 57). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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21 Jun 2019 |
The primary reasons for this amendment were to improve the feasibility of the diary compliance requirement, to clarify the exclusion criterion for nerve stimulation or device, and to clarify the timing of injection site reaction assessment. |
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05 Dec 2019 |
The primary reason for this amendment was to update the protocol with the dose to be used for participants <45.0 kg (120 mg SC monthly) following the completion of the Phase 1 pediatric pharmacokinetic study (TV48125-CNS-10141). |
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20 Apr 2020 |
The primary reason for this amendment was to revise an exclusion criterion to exclude participants with a history of Stevens-Johnson Syndrome or toxic epidermal necrolysis syndrome. |
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20 Aug 2020 |
The primary reason for this amendment was to provide guidance for remote assessments to minimize the time that participants and caregivers were required to spend at the study site. This consideration was triggered by the COVID-19 pandemic; however, remote assessments could be carried out on a regular basis to provide flexibility for participants, caregivers, and site staff. Patient reported outcomes assessed in this study, including the PedMIDAS, PedsQL, and Patient Global Impression of Improvement (PGI-I), as well as the C-SSRS, were valid to be conducted remotely, as confirmed by the scale authors. Instructions on remote data collection were available in the site operational manual. |
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09 Dec 2021 |
The primary reason for this amendment was to revise the protocol to allow combined oral progestin and estrogen contraceptives, to expand the body mass index (BMI) upper limit to 120% of the 95th percentile in order reflect the real-world participant population, and to clarify potential sample size changes subsequent to the planned interim analysis. |
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24 Sep 2023 |
- The primary reason for this amendment was to reduce the size of the study population and to update the inclusion criteria in order to help with enrollment and study completion.
- Updated study timelines according to new projections and reduced study population. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
