The Effect of Anti-calcitonin Gene-related Peptide (CGRP) Receptor Antibodies on the Headache Inducing Properties of CGRP and Cilostazol in Migraine Patients

A randomized, double-blind, placebo-controlled, parallel study to investigate the effect of erenumab in calcitonin-gene related peptide and cilostazol experimental models of migraine in humans. Followed by a 6-month open-label extension.

Study Overview

• Status: Unknown
• Conditions: Migraine; Migraine Without Aura; Migraine With Aura
• Intervention / Treatment: Drug: Erenumab; Drug: Calcitonin gene-related peptide; Drug: Cilostazol; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 72
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Thien P Do, MD; Phone Number: 004541414117; Email: tdoo0001@regionh.dk

Study Locations

• Denmark
  • Glostrup, Denmark, 2600
    • Recruiting
    • Danish Headache Center
    • Contact: Thien P Do, MD; Phone Number: 004541414117; Email: tdoo0001@regionh.dk
    • Sub-Investigator: Thien P Do, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 58 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with migraine with or without aura according to the International Classification of Headache Disorders with a frequency of ≥4 migraine days per month
• 50-100 kg weight
• Participants of childbearing potential must use safe contraception (birth control) or be sexually abstinent

Exclusion Criteria:

• Any other primary headache disorder according to the International Classification of Headache Disorders except for tension-type headache
• Any secondary headache disorder according to the International Classification of Headache Disorders
• Migraine attack during the preceding 48 hours on provocation day
• Headache during the preceding 24 hours on provocation day
• Treatment with monoclonal antibodies or participation in clinical trials with monoclonal antibodies during the preceding year
• Daily consumption of any other drug/medication than oral contraception (birth control)
• Consumption of any other drug/medication later than four times the plasma half-time of the drug on provocation day except for oral contraception
• Pregnant or active breastfeeding participants
• Any cardiovascular diseases including cerebrovascular disorders
• Information in patient history or during physical examination indicating psychiatric disorders or substance abuse
• Information in patient history or during physical examination that the screening physician deems relevant for participation in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Randomized treatment phase: Erenumab; Erenumab 140 mg single subcutaneous injection at baseline	Drug: Erenumab; Subcutaneous injection of 140 mg erenumab.; Other Names: Aimovig®; Drug: Calcitonin gene-related peptide; Intravenous infusion of 1.5ug/min calcitonin gene-related peptide over 20 minutes.; Drug: Cilostazol; Oral intake of 200 mg cilostazol.
Placebo Comparator: Randomized treatment phase: Placebo; Saline placebo single subcutaneous injection at baseline	Drug: Calcitonin gene-related peptide; Intravenous infusion of 1.5ug/min calcitonin gene-related peptide over 20 minutes.; Drug: Cilostazol; Oral intake of 200 mg cilostazol.; Drug: Placebo; Subcutaneous injection of saline placebo.; Other Names: Saline placebo
Other: Open-label extension treatment phase: Erenumab; Erenumab 140 mg monthly subcutaneous injection for six months after completion of the randomized, double-blinded, placebo-controlled study phase during the open-label extension	Drug: Erenumab; Subcutaneous injection of 140 mg erenumab.; Other Names: Aimovig®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Migraine-like attack	The incidence of migraine-like attack after administration of calcitonin-gene related peptide or cilostazol in patients with migraine pretreated with erenumab compared to patients with migraine pretreated with placebo. A migraine-like attack is defined attack fulfilling either (i) or (ii): (i) Headache fulfilling criteria C and D for migraine without aura according to the International Headache Society criteria: C. Headache has at least two of the following characteristics: unilateral location; pulsating quality; moderate or severe pain intensity (moderate to severe pain intensity is considered ≥4 on verbal rating scale); aggravation by cough (in-hospital phase) or causing avoidance of routine physical activity (out-hospital phase); D. During headache at least one of the following: nausea and/or vomiting; photophobia and phonophobia; and (ii) Headache described as mimicking the patient's usual migraine attack and treated with acute migraine medication (rescue medication).	Before (-5 min) and after administration of (+12 hours) of experimental trigger

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Headache intensity	Change in headache intensity after administration of calcitonin-gene related peptide or cilostazol in patients with migraine pretreated with erenumab compared to patients with migraine pretreated with placebo. Headache intensity scores are measured by a numerical rating scale (NRS). It is a verbally declared scale from 0 to 10, where 0 is no pain; 10 is the worst pain imaginable.	Before (-5 min) and after administration of (+12 hours) of experimental trigger
Hemodynamics (superficial temporal artery)	Change in diameter (mm) of superficial temporal artery after administration of calcitonin-gene related peptide or cilostazol in patients with migraine pretreated with erenumab compared to patients with migraine pretreated with placebo.	Before (-5 min) and after administration of (+90 minutes) of experimental trigger
Hemodynamics (radial artery)	Change in diameter (mm) of radial artery after administration of calcitonin-gene related peptide or cilostazol in patients with migraine pretreated with erenumab compared to patients with migraine pretreated with placebo.	Before (-5 min) and after administration of (+90 minutes) of experimental trigger
Neuropeptide plasma concentrations (CGRP)	Change in plasma concentrations of calcitonin gene-related peptide (CGRP) after administration of calcitonin-gene related peptide or cilostazol in patients with migraine pretreated with erenumab compared to patients with migraine pretreated with placebo.; Change in plasma concentrations of calcitonin gene-related peptide during the open-label treatment phase.	(1) Before (-5 min) and after administration of (+60 minutes) of experimental trigger; (2) 24-week open-label treatment phase
Neuropeptide plasma concentrations (VIP)	Change in plasma concentrations of vasoactive intestinal peptide (VIP) after administration of calcitonin-gene related peptide or cilostazol in patients with migraine pretreated with erenumab compared to patients with migraine pretreated with placebo.; Change in plasma concentrations of vasoactive intestinal peptide (VIP) during the open-label treatment phase.	(1) Before (-5 min) and after administration of (+60 minutes) of experimental trigger; (2) 24-week open-label treatment phase
Neuropeptide plasma concentrations (PACAP)	Change in plasma concentrations of pituitary adenylate cyclase-activating peptide (PACAP) after administration of calcitonin-gene related peptide or cilostazol in patients with migraine pretreated with erenumab compared to patients with migraine pretreated with placebo.; Change in plasma concentrations of pituitary adenylate cyclase-activating peptide (PACAP) during the open-label treatment phase.	(1) Before (-5 min) and after administration of (+60 minutes) of experimental trigger; (2) 24-week open-label treatment phase
Facial flushing	Change in facial skin flushing after administration of calcitonin-gene related peptide or cilostazol in patients with migraine pretreated with erenumab compared to patients with migraine pretreated with placebo.	Before (-5 min) and after administration of (+90 minutes) of experimental trigger
Facial temperature	Change in facial temperature after administration of calcitonin-gene related peptide or cilostazol in patients with migraine pretreated with erenumab compared to patients with migraine pretreated with placebo.	Before (-5 min) and after administration of (+90 minutes) of experimental trigger
Headache day	Change in number of headache days per month after administration of erenumab from baseline compared to the last 3 months (months 4, 5, and 6) of the 24-week open-label treatment phase.	Baseline and the last 3 months (months 4, 5, and 6) of the 24-week open-label treatment phase
Migraine day	Change in number of migraine days per month after administration of erenumab from baseline compared to the last 3 months (months 4, 5, and 6) of the 24-week open-label treatment phase.	Baseline and the last 3 months (months 4, 5, and 6) of the 24-week open-label treatment phase
≥50% responder rate	Proportion of participants with a ≥50% reduction in number of migraine days per month after administration of erenumab from baseline compared to the last 3 months (months 4, 5, and 6) of the 24-week open-label treatment phase.	Baseline and the last 3 months (months 4, 5, and 6) of the 24-week open-label treatment phase

Collaborators and Investigators

• Sponsor: Danish Headache Center
• Collaborators: Novartis Pharmaceuticals
• Investigators: Study Director: Thien P Do, MD, Danish Headache Center

Study record dates

Study Major Dates

• Study Start (Actual): July 22, 2020
• Primary Completion (Anticipated): February 1, 2022
• Study Completion (Anticipated): July 1, 2022

Study Registration Dates

• First Submitted: June 22, 2020
• First Submitted That Met QC Criteria: June 29, 2020
• First Posted (Actual): July 1, 2020

Study Record Updates

• Last Update Posted (Actual): October 8, 2020
• Last Update Submitted That Met QC Criteria: October 6, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Headache; Migraine without Aura; Migraine with Aura; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Neuroprotective Agents; Protective Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Phosphodiesterase Inhibitors; Calcitonin Gene-Related Peptide Receptor Antagonists; Phosphodiesterase 3 Inhibitors; Erenumab; Cilostazol; Calcitonin; Salmon calcitonin; Calcitonin Gene-Related Peptide; Katacalcin
• Other Study ID Numbers: CGRP2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No