A Functional MRI Study on Erenumab Treatment Effects in Episodic Migraine Patients

NCT03977649 | Completed Phase 4 FDA Drug

• 1 other identifier: CAMG334AIT03
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to investigate the effects of erenumab on central sensitization and brain networks connectivity of migraine patients

Conditions

Migraine Disorders

Keywords

AMG334; erenumab; functional MRI; connectivity

Outcome Measures

Primary Outcomes (2)

• z-score maps change difference between-treatment-groups

  z score maps are measures of resting state functional connectivity strength in the brain areas involved in pain processing

  baseline, month 3, month 6

• z-score maps difference between clinical response groups within the two treatment groups.

  clinical response assessed as reduction by 50% in monthly migraine days ,MMD, in the last month vs baseline. z score maps relative to resting state functional connectivity strength in the brain areas involved in pain processing

  baseline, month 3, month 6

Secondary Outcomes (5)

• Correlation (by treatment groups and in all patients) between the changes in the resting state functional connectivity strength, measured as z-score maps, and clinical outcomes

  month 3, month 6

• Between-treatment-groups difference in change of resting state functional connectivity strength, from baseline to month 3 of treatment, measured as z-score maps. in the brain regions involved in migraine symptoms

  baseline, month 3, month 6

• Correlation (by treatment group and in all patients) between of the changes in the resting state functional connectivity strength of the areas involved in migraine symptoms and the reduction of the respective symptoms

  month 3, month 6

• Baseline resting state functional connectivity strength will be evaluated by treatment group and in all patients as potential predictors of treatment clinical response defined by the achievement of at least 50% reduction of monthly migraine days

  baseline, month 3, month 6

• Changes in z-score maps from baseline to month 3 of erenumab treatment and from baseline to month 6 with 3 months with erenumab followed by 3 months of placebo

  baseline, month 3, month 6

Study Arms (2)

erenumab

EXPERIMENTAL

monthly subcutaneous erenumab 140 mg for 12 weeks

Drug: erenumab

placebo

PLACEBO COMPARATOR

monthly subcutaneous masked placebo for 12 weeks.

Drug: placebo

Interventions

erenumab DRUG

erenumab 140 mg sc every 4 weeks

erenumab

placebo DRUG

placebo sc every 4 weeks

placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent must be obtained prior to participation in the study History of migraine with or without aura for at least 12 months prior to screening 4. Migraine frequency: ≥ 4 and \< 15 migraine days per month on average across the 3 months prior to screening and confirmed during the baseline phase based on diary calculation
• Headache frequency: \<15 headache days per month on average across the 3 months prior to screening and confirmed during the baseline phase based on diary calculation
• Failure to 2 or more previous treatment categories locally indicated for migraine prophylaxis due to either lack of efficacy or poor tolerability

You may not qualify if:

• History of cluster headache or hemiplegic migraine headache
• History of chronic pain disorders and neuropathic pain
• History of head trauma or seizure or major psychiatric disorders or suicidal ideation/behavior at any time before screening
• Currently, receiving any other prophylactic treatment for migraine and/or prohibited medications, non-pharmacologic interventions or devices (any substance, non-pharmacologic intervention or device acting at central nervous system), or less than 60 days or 5 half-lives prior to the start of the baseline period, during the baseline period, or treatment period
• Exposure to botulinum toxin in the head and/or neck region within 4 months prior to the start of the baseline period, during the baseline period, or treatment period.
• Taken the following for any indication in any month during the 2 months prior to the start of the baseline period:
• Ergotamines or triptans on ≥ 10 days per month, or
• Simple analgesics (non-steroidal anti-inflammatory drugs \[NSAIDs\], acetaminophen) on ≥ 15 days per month, or
• Opioid- or butalbital-containing analgesics on ≥4 days per month.
• Previous exposure to erenumab or exposure to any other prophylactic CGRP-targeted therapy (prior to and during the study)
• History or evidence of any other unstable or clinically significant medical condition that in the opinion of the investigator would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion
• Subject has any clinically significant vital sign, laboratory, or electrocardiogram (ECG) abnormality during screening that, in the opinion of the investigator, could pose a risk to subject safety or interfere with the study evaluation
• Evidence of drug or alcohol abuse or dependence within 12 months prior to screening, based on medical records or patient self-report
• Pregnant or breastfeeding
• All the clinical conditions for which undergoing an MRI scan is contraindicated

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (5)

Novartis Investigative Site

Milan, MI, 20132, Italy

Location

Novartis Investigative Site

Milan, MI, 20133, Italy

Location

Novartis Investigative Site

Pavia, PV, 27100, Italy

Location

Novartis Investigative Site

L’Aquila, Italy

Location

Novartis Investigative Site

Napoli, 80138, Italy

Location

MeSH Terms

Conditions

Migraine Disorders

Interventions

erenumab

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Study treatments will be all identical in packaging, labeling, schedule of administration, appearance, taste and odor
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: After a run-in phase of 4 weeks, patients will be randomized, according to a 1:1 ratio, to a 24 weeks of treatment, as follow: * Sequence 1: A/B * Sequence 2: B/A where: A=monthly subcutaneous erenumab 140 mg for 12 weeks; B=monthly subcutaneous masked placebo for 12 weeks.

Study Record Dates

• First Submitted: June 4, 2019
• First Posted: June 6, 2019
• Study Start: July 30, 2019
• Primary Completion: July 5, 2021
• Study Completion: July 5, 2021
• Last Updated: August 13, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will share

Locations

IT (5)