A Multicenter Assessment of LBR-101 in High Frequency Episodic Migraine

• ClinicalTrials.gov Identifier: NCT02025556
• Recruitment Status: Completed
• First Posted: January 1, 2014
• Results First Posted: January 24, 2022
• Last Update Posted: January 24, 2022
• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
• Collaborator: NCGS, Inc.
• Information provided by (Responsible Party): Teva Branded Pharmaceutical Products R&D, Inc.

Tracking Information

• First Submitted Date: December 20, 2013
• First Posted Date: January 1, 2014
• Results First Submitted Date: December 1, 2021
• Results First Posted Date: January 24, 2022
• Last Update Posted Date: January 24, 2022
• Actual Study Start Date: January 31, 2014
• Actual Primary Completion Date: January 31, 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 18, 2022)

• Mean Change From Baseline in the Monthly Migraine Days During the 28-day Post Treatment Period Ending With Week 12 [ Time Frame: Baseline to week 12 ]
  A migraine day was endorsed when at least 1 of the following situations occurred: 1) A calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache endorsing criteria for migraine, or 2) a calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache endorsing criteria for probable migraine, a migraine subtype where only one migraine criterion is missing, or 3) the participant used acute migraine medication (triptans and ergot compounds) to treat a headache of any duration, or 4) any of the above days preceded or followed by a day with a headache of any duration. This calculation was defined as the change from baseline in the number of headache days during the 28-day post treatment period ending at week 12. Headache severity was rated daily by the participant as either no pain, mild, moderate, or severe.
• Number of Participants With at Least One Adverse Event [ Time Frame: Baseline 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 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.
• Number of Participants Reporting Mild, Moderate, and Severe Adverse Events (AEs) [ Time Frame: Up to week 12 ]
  Adverse events were rated based on the investigator's clinical judgment. Mild: awareness of a sign or symptom that was easily tolerated Moderate: sign or symptom intense enough to interfere with usual activity Severe: interfered significantly with ability to do work or usual activity

Original Primary Outcome Measures (submitted: December 30, 2013)

• Efficacy of two distinct doses of subcutaneous LBR-101 in the preventive treatment of HFEM, measured by mean change from baseline in the monthly migraine days during the 28-day post treatment period ending with week 12 [ Time Frame: 12 weeks after first dose of blinded study drug ]
• Evaluate the safety and tolerability (ie: by measuring the change from baseline in the frequency and severity of adverse events) of LBR-101 in the preventive treatment of HFEM. [ Time Frame: 12 weeks after first dose of blinded study drug ]

Current Secondary Outcome Measures (submitted: January 18, 2022)

Change From Baseline in Number of Days With Headache of Any Severity [ Time Frame: Baseline to week 12 ]

A headache day was defined as when at least 1 of the following situations occurred: A calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache of any severity or the participant used acute migraine medication (triptans and ergot compounds) to treat a headache. This calculation was defined as the change from baseline in the number of headache days during the 28-day post treatment period ending at week 12. Headache severity was rated daily by the participant as either no pain, mild, moderate, or severe.

• Original Secondary Outcome Measures (submitted: December 30, 2013): Efficacy of two distinct doses of subcutaneous LBR-101 in the preventive treatment of HFEM, measured by mean change from baseline on the number of days with headache of any severity during the 28-day post treatment period ending with week 12 [ Time Frame: 12 weeks after first dose of blinded study drug ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Multicenter Assessment of LBR-101 in High Frequency Episodic Migraine
• Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Study Comparing the Efficacy and Safety of Two Doses of Subcutaneous LBR-101 With Placebo for the Preventive Treatment of High Frequency Episodic Migraine
• Brief Summary: The purpose of this study is to determine whether monthly subcutaneous administration of LBR-101 (fremanezumab) is safe and provides migraine prevention in subjects with high frequency episodic migraine.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Episodic Migraine Headache

Intervention

• Drug: LBR-101 High Dose
  Subcutaneously Administered High Dose LBR-101 Monthly x 3
  Other Name: Fremanezumab
• Drug: LBR-101 Low Dose
  Subcutaneously Administered Low Dose LBR-101 Monthly x 3
  Other Name: Fremanezumab
• Drug: Placebo
  Subcutaneously Administered Placebo (Vehicle) Monthly x 3

Study Arms

• Experimental: LBR-101 High Dose
  Subcutaneous High Dose LBR-101 Administered Monthly x 3
  Intervention: Drug: LBR-101 High Dose
• Experimental: LBR-101 Low Dose
  Subcutaneous Low Dose LBR-101 Administered Monthly x 3
  Intervention: Drug: LBR-101 Low Dose
• Placebo Comparator: Placebo
  Subcutaneous Placebo Administered Monthly x 3
  Intervention: Drug: Placebo

Publications *

• Silberstein SD, Rapoport AM, Loupe PS, Aycardi E, McDonald M, Yang R, Bigal ME. The Effect of Beginning Treatment With Fremanezumab on Headache and Associated Symptoms in the Randomized Phase 2 Study of High Frequency Episodic Migraine: Post-Hoc Analyses on the First 3 Weeks of Treatment. Headache. 2019 Mar;59(3):383-393. doi: 10.1111/head.13446. Epub 2018 Nov 18.
• VanderPluym J, Dodick DW, Lipton RB, Ma Y, Loupe PS, Bigal ME. Fremanezumab for preventive treatment of migraine: Functional status on headache-free days. Neurology. 2018 Sep 18;91(12):e1152-e1165. doi: 10.1212/01.wnl.0000544321.19316.40. Epub 2018 Aug 17.
• Halker Singh RB, Aycardi E, Bigal ME, Loupe PS, McDonald M, Dodick DW. Sustained reductions in migraine days, moderate-to-severe headache days and days with acute medication use for HFEM and CM patients taking fremanezumab: Post-hoc analyses from phase 2 trials. Cephalalgia. 2019 Jan;39(1):52-60. doi: 10.1177/0333102418772585. Epub 2018 May 3.
• Cohen JM, Dodick DW, Yang R, Newman LC, Li T, Aycardi E, Bigal ME. Fremanezumab as Add-On Treatment for Patients Treated With Other Migraine Preventive Medicines. Headache. 2017 Oct;57(9):1375-1384. doi: 10.1111/head.13156. Epub 2017 Sep 1.
• Bigal ME, Dodick DW, Rapoport AM, Silberstein SD, Ma Y, Yang R, Loupe PS, Burstein R, Newman LC, Lipton RB. Safety, tolerability, and efficacy of TEV-48125 for preventive treatment of high-frequency episodic migraine: a multicentre, randomised, double-blind, placebo-controlled, phase 2b study. Lancet Neurol. 2015 Nov;14(11):1081-90. doi: 10.1016/S1474-4422(15)00249-5. Epub 2015 Sep 30.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 8, 2021): 297
• Original Estimated Enrollment (submitted: December 30, 2013): 270
• Actual Study Completion Date: March 31, 2015
• Actual Primary Completion Date: January 31, 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Males or females aged 18 to 65 years of age.
• A signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study including any known and potential risks and available alternative treatments.

• Subjects fulfilling criteria for episodic migraine as per the Second Edition of The International Headache Society (Olesen and Steiner 2004), who experience migraine at high frequency as follows:

  i. History of headaches on more than 8 days per month for at least 3 months prior to screening

ii. Verification of headache frequency through prospectively collected baseline information during the 28-day run-in phase demonstrating headaches (of any type) on at least 8 days with at total of 8 to 14 days* fulfilling criteria for migraine.

*Operational definition for migraine and probable migraine days are presented in the statistical section of this protocol.

• Body Mass Index (BMI) of 17.5 to 37.5 kg/m2, and a total body weight between 50 kg and 120 kg, inclusive.
• Demonstrated compliance with the electronic headache diary during the run-in period by entry of headache data on a minimum of 22/28 days (80% compliance).

Exclusion Criteria:

• Subject has received onabotulinum toxin A for migraine or for any medical or cosmetic reasons requiring injections in the head, face, or neck during the six months prior to screening.
• Subject uses medications containing opioids (including codeine) or barbiturates (including Fiorinal®, Fioricet®, or any other combination containing butalbital) on more than 4 days per month for the treatment of migraine or for any other reason.
• Failed > 2 medication categories or > 3 preventive medications (within two medication categories) due to lack of efficacy for prophylactic treatment of episodic or chronic migraine after an adequate therapeutic trial
• Treatment with an investigational drug or device within 30 days of study entry or any prior exposure to a monoclonal antibody targeting the CGRP pathway.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02025556
• Other Study ID Numbers: LBR-101-022
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Teva Branded Pharmaceutical Products R&D, Inc.
• Original Responsible Party: Labrys Biologics Inc.
• Current Study Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
• Original Study Sponsor: Labrys Biologics Inc.
• Collaborators: NCGS, Inc.

Investigators

• Study Director: Teva Medical Expert, MD; Teva Pharmaceuticals USA

• PRS Account: Teva Branded Pharmaceutical Products R&D, Inc.
• Verification Date: January 2022