Study of Erenumab in Adults with Chronic Migraine and MOH

• Research type

  Research Study

• Full title

  A Phase 4, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Erenumab in Adults With Chronic Migraine and Medication Overuse Headache

• IRAS ID

  257176

• Contact name

  Peter Goadsby

• Contact email

  peter.goadsby@kcl.ac.uk

• Sponsor organisation

  Amgen Ltd

• Eudract number

  2018-003342-16

• Clinicaltrials.gov Identifier

  NCT03971071

• Duration of Study in the UK

  2 years, 7 months, 27 days

• Research summary

  20170703 is a study in adult participants with Chronic Migraine (CM) and Medication Overuse Headache (MOH). The purpose of conducting the study is to better understand the effectiveness and safety of erenumab compared to placebo when given to a targeted population diagnosed with CM and MOH that have at least one preventative treatment failure, to see if it makes any changes in the number of days participants suffer from monthly headache days (MHD) and are able to revert the medication overuse status.

  After consenting, participants will enter the screening period (up to 7 weeks), following which eligible participants (approximately 687) will be randomised in a 1:1:1 fashion to either placebo, erenumab 70mg or erenumab 140mg for 24 weeks (double blind treatment phase (DBTP)), the participants then have the option to enter the open-label treatment phase (OLTP) for 28 weeks. Participants on erenumab will continue with the same treatment whereas those participants previously on placebo will be randomised into either erenumab 70mg or erenumab 140mg. At the end of treatment, participants will have an End of Study visit 4 weeks after the last dose.

  Participants are expected to complete 12 on site study visits and 4 telephone calls. The planned length of participation for each participant is up to 59 weeks.

  Participants will use an electronic diary daily during the DBTP and then part of the OLTP in order to collect information about headaches, medication and complete questionnaires.

  Erenumab works by blocking a cell receptor, which is a key factor in causing migraines. Participants that suffer from migraines, frequently take pain medication that overtime can become less effective in treating migraines and lead to a condition known as MOH, by taking erenumab the study is trying to see if it will revert the medication overuse status.

  Lay summary of study results: Clinical Study Results

  1. Study Name
  Title of the Study: A Phase 4, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Erenumab in Adults With Chronic Migraine and Medication Overuse Headache
  Brief Title: A Study to Evaluate the Efficacy and Safety of Erenumab in Adults With Medication Overuse Headache
  Protocol Number: 20170703
  EU Trial Number: 2018-003342-16
  Other Identifiers: NCT03971071
  Date of This Summary: 02 April 2024

  What does this summary cover?
  This summary shows the main results from 1 clinical study. The results are only for this study. Other studies may find different results. Researchers and health authorities look at the results of many studies to decide which medicines work best and are safest for patients.
  Amgen has committed to make research results available to the public. This summary has been provided as part of that commitment and should not be used for any other purpose. It should not be considered to make a claim for any product or to guide treatment decisions.
  Some information in this summary may be different from the approved labelling for erenumab. Your healthcare professional should refer to the full prescribing information for proper use of erenumab.

  2. Who Sponsored This Study?

  Amgen Inc.
  One Amgen Center Drive
  Thousand Oaks, CA 91320-1799 USA Phone (United States): +1 805-447-1000 Amgen Inc. is the sponsor of the study who made erenumab, the medicine tested in the study. Amgen would like to thank everyone who participated in this study and feels it is important to share the results of this study.

  3. General Information About the Clinical Study

  Where and when was the study done?

  • This study took place in Austria, Czech Republic, Finland, France, Hungary, Italy, Poland, Portugal, Spain, United Kingdom, Australia, and United States.
  • The study began in October 2019 and ended in June 2023.
  • The study was completed as planned.

  Why was the study done?

  • Chronic migraine is a condition where people have frequent or long-lasting episodes of headaches and migraines. With chronic migraines, a person’s symptoms can shift daily (or even hour to hour). The repeated use of pain medications (for example simple pain reliever, prescription medication and/or opioids) for a long period of time may lead to more frequent and severe headaches, also known as chronic migraine-medication overuse headaches (CM-MOH).
  • Calcitonin gene-related peptide (CGRP) is a brain hormone thought to be implicated in migraines. In the brain, increased levels of CGRP can cause expansion (dilation) of blood vessels and inflammation, leading to the headache symptoms.
  • Erenumab works by blocking the receptors for CGRP in the body to either prevent migraines/headaches, reduce the likelihood of a migraine to occur, or decrease the severity of migraines.
  • This was a phase 4 study, which is an additional study done after a medicine has been approved by a government health authority for doctors to prescribe to patients. Researchers compared the study medicine, erenumab, to a placebo. A placebo does not contain any medicine but does contain other parts of the solution used in the study medicine, which is called a matched placebo. Matched placebo injections help researchers understand if the study medicine is effective or if any improvements are just because of natural changes in health over time.
  • The main purpose of this study was to see if erenumab provides additional beneficial effects in CM-MOH participants as compared to placebo. The study key measurement was achievement of MOH remission at month 6 as compared to placebo.

  4. Who Was Included in This Study?

  Who took part in the study?

  This study enrolled 620 participants with MOH. 510 participants (82%, or about
  82 out of 100) were women and 110 participants (18%, or about 18 out of 100) were men. They ranged in age from 18 to 82 years.

  This study took place at 67 study centers across Austria, Czech Republic, Finland, France, Hungary, Italy, Poland, Portugal, Spain, United Kingdom, Australia, and United States.
  The number of participants enrolled in each country are shown below:
  NORTH AMERICA:
  United States: 47

  EUROPE:
  Austria: 10
  Czech Republic: 121
  Finland: 33
  France: 105
  Hungary: 60
  Italy: 57
  Poland: 88
  Portugal: 46
  Spain: 46
  United Kingdom: 6

  OCEANIA:
  Australia: 1

  Participants were examined by a study doctor and chosen to be in the study if they:
  • Were 18 years or older
  • Had a history of migraine for at least 12 months before the study screening
  • Had a history of chronic migraine for at least 6 months before the study screening
  • Were diagnosed with MOH by a doctor
  • Had a history of treatment failure for chronic migraines, with at least 1 preventive treatment
  • Met these additional criteria in the 28 days before being given study medicine (the baseline period):
  o had at least 14 headache days, including 8 or more migraine days
  o overused their migraine medicine
  o took headache medicine on at least 2 days per week for each week
  o completed the electronic diary (eDiary) on at least 23 days

  5. Which Medicines Were Studied?

  • In this study, 2 commercially available doses of erenumab were compared to placebo. Neither the participants nor the study doctors could choose which treatment participants were given. Participants agreed to be put into a group by chance (ie, at random or “randomized”). The process of randomized treatment allocation is like the rolling of a dice or drawing numbers out of a hat and is automatically generated by a computer without interference from the doctor or site staff.
  • This was a “double-blind” study, which means that the participants and the study doctors could only find out whether the participant was given erenumab or placebo after the study was over and information provided by participants could no longer be changed. This is done to make sure that knowledge about study treatment would not influence reported results in any way.
  • At the beginning of the study (screening period), participants were separated into 2 groups (“cohorts”) based on their history of opioid medication use.
  • Within each cohort, participants were randomly placed into 1 of 3 treatment groups and received either 70 mg of erenumab, 140 mg of erenumab, or placebo once a month between week 0 and week 24. There was a 2 out of 3 chance of being placed in an erenumab treatment group.
  • At the end of the double-blind treatment part of the study, participants were offered an opportunity to take part in an “open-label” part of the study where everyone received erenumab. During the open-label part of the study both the participant and the doctor knew which medicine and how much medicine was being given. The open-label part was an exploratory phase of the study and measurements made at this phase were not part of the analysis of key study results.

  • The number of participants in each treatment group is shown below:
  SCREENING (includes an initial Screening period and baseline period): Up to 3 weeks for the screening period and 4 weeks baseline period
  • 620 participants:
  - Cohort A: 584 nonopioid – treated participants
  - Cohort B: 36 opioid – treated participants

  GROUPS (Randomised):
  • Erenumab (414 participants, *2 participants did not receive erenumab)
  • Placebo (206 participants)

  DOUBLE - BLIND TREATMENT: Weeks 0 to 24
  • 70mg Erenumab (every month, 206 participants)
  • 140mg Erenumab (every month, 206 participants)
  • Placebo (every month, 206 participants)

  OPTIONAL OPEN-LABELLED TREATMENT: Weeks 24 to 52
  • 70mg (every month, 291 participants)
  • 140mg Erenumab (every month, 296 participants)

  587 participants continued in the open-labelled part of the study and were given either 70mg or 140mg of Erenumab.

  6. What Were the Side Effects?

  What is a side effect?

  All medicines can cause side effects, or unwanted medical problems that may happen when you take a medicine. In this study, doctors reported all the medical problems participants had. Doctors believed some of the problems could have been caused by the study medicine(s). These possible side effects are listed below.

  What side effects were seen?

  When reporting side effects during the double-blind part of this study, the study doctor did not know which study medicine a participant was receiving.
  The tables below show how many participants had side effects.

  Side Effects During the Double-blind Part of the Study
  70 mg Erenumab (206 participants)
  140 mg Erenumab (206 participants)
  Placebo (206 participants)

  How many participants had serious side effects?
  70 mg Erenumab (206 participants) - 0 participants (0%)
  140 mg Erenumab (206 participants) - 0 participants (0%) Placebo (206 participants) - 1 participant (less than 1%)

  How many participants had non- serious side effects?
  70 mg Erenumab (206 participants) - 65 participants (32%)
  140 mg Erenumab (206 participants) - 64 participants (31%) Placebo (206 participants) - 35 participants (17%)

  How many participants died from side effects?
  70 mg Erenumab (206 participants) - 0 participants (0%)
  140 mg Erenumab (206 participants) - 0 participants (0%) Placebo (206 participants) - 0 participants (0%)

  How many participants stopped taking the study medicine because of side effects?
  70 mg Erenumab (206 participants) - 3 participants (2%)
  140 mg Erenumab (206 participants) - 3 participants (2%) Placebo (206 participants) - 2 participants (1%)

  Side Effects During the Open-label Part of the Study
  70 mg Erenumab (291 participants)
  140 mg Erenumab (296 participants)

  How many participants had serious side effects?
  70 mg Erenumab (291 participants) - 0 participants (0%)
  140 mg Erenumab (296 participants) - 1 participant (less than 1%)

  How many participants had non- serious side effects?
  70 mg Erenumab (291 participants) - 59 participants (20%)
  140 mg Erenumab (296 participants) - 57 participants (19%)

  How many participants died from side effects?
  70 mg Erenumab (291 participants) - 0 participants (0%)
  140 mg Erenumab (296 participants) - 0 participants (0%)

  How many participants stopped taking the study medicine because of side effects?
  70 mg Erenumab (291 participants) - 1 participant (less than 1%)
  140 mg Erenumab (296 participants) - 3 participants (1%)

  A side effect was serious if a participant had to stay in the hospital, experience substantial disruption in the ability to conduct normal life functions, died, or was at risk of death because of a side effect. No participants died during the study.
  The table below shows the serious side effects.

  Serious Side Effects During the Double-blind Part of the Study

  Serious side effect
  70 mg Erenumab (206 participants)
  140 mg Erenumab (206 participants)
  Placebo (206 participants)

  Heart Attack
  70 mg Erenumab (206 participants) - 0 participants (0%)
  140 mg Erenumab (206 participants) - 0 participants (0%) Placebo (206 participants) - 1 participant (less than 1%)

  Serious Side Effects During the Open-label Part of the Study

  Serious side effect
  70 mg Erenumab (291 participants)
  140 mg Erenumab (296 participants)

  Temporary Stroke
  70 mg Erenumab (291 participants) - 0 participants (0%)
  140 mg Erenumab (296 participants) - 1 participant (less than 1%)

  The tables below show the non-serious side effects that occurred in more than 2% of the participants (or about 2 out of 100) during the double-blind and open-label part of the study.

  Non-serious Side Effects During the Double-blind Part of Study

  Non-serious side effect
  70 mg Erenumab (206 participants)
  140 mg Erenumab (206 participants)
  Placebo (206 participants)

  Constipation
  70 mg Erenumab (206 participants) - 27 participants (13%)
  140 mg Erenumab (206 participants) - 30 participants (15%) Placebo (206 participants) - 8 participants (4%)

  Redness at site of injection
  70 mg Erenumab (206 participants) - 6 participants (3%)
  140 mg Erenumab (206 participants) - 7 participants (3%) Placebo (206 participants) - 3 participants (2%)

  Firmness of skin at site of injection
  70 mg Erenumab (206 participants) - 2 participants (1%)
  140 mg Erenumab (206 participants) - 5 participants (2%) Placebo (206 participants) - 3 participants (2%)

  Pain at site of injection
  70 mg Erenumab (206 participants) - 9 participants (4%)
  140 mg Erenumab (206 participants) - 9 participants (4%) Placebo (206 participants) - 6 participants (3%)

  Non-serious Side Effects During the Open-label Part of Study Non-serious side effect
  70 mg Erenumab (291 participants)
  140 mg Erenumab (296 participants)

  Constipation
  70 mg Erenumab (291 participants) - 20 participants (7%)
  140 mg Erenumab (296 participants) - 22 participants (7%)

  Redness at site of injection
  70 mg Erenumab (291 participants) - 13 participants (5%)
  140 mg Erenumab (296 participants) - 9 participants (3%)

  Firmness of skin at site of injection
  70 mg Erenumab (291 participants) - 2 participants (less than 1%)
  140 mg Erenumab (296 participants) - 5 participants (2%)

  Pain at site of injection
  70 mg Erenumab (291 participants) - 6 participants (2%)
  140 mg Erenumab (296 participants) - 7 participants (2%)

  Itching at site of injection
  70 mg Erenumab (291 participants) - 2 participants (less than 1%)
  140 mg Erenumab (296 participants) - 6 participants (2%)

  This section only shows the most often reported side effects considered by the study doctor as related to study medicine. No single clinical study can give a complete picture of the benefits and risks of a medicine. Information about other side effects may be available at the websites listed at the end of this summary.

  7. What Were the Overall Results of the Study?

  Did erenumab have an effect compared with placebo in achieving MOH remission?

  • To answer this question, the researchers observed if there was an absence of MOH at month 6. An absence of MOH was considered to be when the average monthly acute headache medication days (AHMD) were less than 10 days over months 4, 5, and 6, or the average monthly headache days were less than 14 days over months 4, 5, and 6. An AHMD was defined as a calendar day when the participant took at least 1 acute headache medicine.
  • The researchers looked at the results from the non-opioid treated cohort of participants during the double-blind part of the study to answer this question. This cohort included 194 participants treated with 70 mg of erenumab, 194 participants treated with 140 mg erenumab, and 194 participants treated with placebo.
  • In this study, 117 participants (60%) treated with 70 mg of erenumab, 134 participants (69%) treated with 140 mg of erenumab, and 102 participants (53%) treated with placebo achieved absence of MOH at month 6.
  • The results for the 140 mg erenumab-treated participants were not likely due to chance.
  • The results did not statistically show that treatment with 70 mg of erenumab was better than placebo. The differences seen could have been due to chance.
  • This study was completed as planned.
  • More results may be available at the websites listed at the end of this summary.

  8. How Has This Study Helped Participants and Researchers?

  What else is important to know about these results?
  These results are only for this clinical study, which looked at a sample of 620 people with MOH. Not all participants in the study had the same outcome. The outcome for any single participant could have been better or worse than the results for their group. Other studies may find different results. These results do not explain how a study medicine may work for each individual person. Many studies are usually needed to allow for a characterization of benefits and risks of a medicine in its intended indication. Erenumab is approved for the prevention of migraine in adults on the basis of multiple studies that had been previously completed involving participants with both episodic and chronic migraine. This research may help future participants and families by helping doctors understand more about the study medicine being studied.

  9. Are There Plans for Further Studies?

  If more clinical studies are done, they may be listed on public websites, such as those below. Search for erenumab (Aimovig®) on the websites below.

  10. Where Can I Find More Information About This Study?

  To find out more about this study, check these websites:

  • https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrialsregister.eu%2F&data=05%7C02%7Criverside.rec%40hra.nhs.uk%7C4d4dc743973849611b2a08dc8edb24dd%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638542319069897422%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=r86pbOz%2BCm2jZb0R%2FzMa6dThfaiGG%2BVdk%2BIXV33ldXs%3D&reserved=0. Use the study identifier 2018-003342-16.
  • https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrials.gov%2F&data=05%7C02%7Criverside.rec%40hra.nhs.uk%7C4d4dc743973849611b2a08dc8edb24dd%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638542319069901102%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=Ev3kk3IfQLg9AblYlZW0st2Tju%2FdCOHzhX9L8LDnstQ%3D&reserved=0. Use the study identifier NCT03971071

  If you participated in the study and have questions about the study results, the doctor or staff at your study center may be able to answer them.

• REC name

  London - Riverside Research Ethics Committee

• REC reference

  19/LO/1381

• Date of REC Opinion

  2 Oct 2019

• REC opinion

  Further Information Favourable Opinion