Randomized, Double-Blind, Placebo-Controlled, Multiple-Attack Study with an Open-Label Extension to Evaluate the Efficacy, Safety, Tolerability, and the Consistency of Effect of Atogepant for the Acute Treatment of Migraine (ECLIPSE)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AbbVie Deutschland GmbH & Co. KG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

3 Apr 2024 → ongoing

Decision date (initial)

2024-03-25

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AbbVie Inc.

External identifiers

EU CT number

2023-506029-12-00

ClinicalTrials.gov

NCT06241313

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Safety

The primary objective of the trial is to evaluate the efficacy of a single dose of atogepant compared to placebo for the acute treatment of a single migraine attack. The first migraine attack during the DB treatment period will be used to assess efficacy of a single attack.

Secondary objectives 1

1. The secondary objective of the trial is to evaluate the safety and tolerability of atogepant for the acute treatment of migraine for a single attack and across multiple migraine attacks, and to evaluate the consistency of effect across multiple attacks.

Conditions and MedDRA coding

Migraine

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

AbbVie is committed to responsible clinical trial data sharing. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information. To learn more about the process, or to submit a request, visit https://www.abbvieclinicaltrials.com/hcp/data-sharing/ For details on when studies are available for sharing, visit https://vivli.org/ourmember/abbvie/

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Subjects must voluntarily sign and date an informed consent, approved by an IEC/IRB, prior to the initiation of any screening or study-specific procedures.
2. Female subjects (or individuals) of childbearing potential must practice at least 1 protocol-specified method of birth control, from 30 days prior to Visit 2/Randomization until 30 days after the last dose of study drug. Female subjects of nonchildbearing potential do not need to use birth control.
3. Has used prescription or nonprescription medication for the acute treatment of migraine in the past.
4. Oral migraine medications used for prophylaxis on-label or off-label (e.g., topiramate, amitriptyline, beta blockers, flunarizine, venlafaxine, etc.), and injectable onabotulinum toxin A and other therapies used for migraine prevention are permitted provided that the treatment is stable for at least 3 months prior to Visit 2/Randomization and continues without change in dose throughout the study.
5. Subjects enrolling in the Triptan-Unsuitable substudy (applicable only after completion of enrollment in the main study) must meet all the inclusion criteria listed for the main study and must not meet any of the exclusion criteria listed for the main study. In addition, subjects must meet the following inclusion criterion: Subject must be ""triptan-unsuitable"" defined as meeting 1 of the 2 following criteria: -has a contraindication to triptans based upon local label and investigator judgment, irrespective of prior triptan use OR meets the following triptan failure definition for ≥2 different triptans: Currently uses a triptan or has used a triptan in the past and has not achieved pain relief (defined as the reduction of a moderate/severe migraine headache to a mild headache or no headache) at 2 hours postdose in ≥2 out of 4 attacks based upon subject interview and investigator judgment OR -Used a triptan in the past but no longer uses a triptan due to AEs based upon subject interview and investigator judgment.
6. Ability and willingness to read, understand, and complete study questionnaires and eDiary.
7. Aged 18 to 75 years, inclusive, at Visit 1/Screening (subjects must also meet the legal age of majority per local law).
8. History of migraine (with or without aura) according to the ICHD-3 for ≥12 months prior to Visit 1/Screening.
9. Migraine onset before the age of 50.
10. History of migraines lasting between 4 to 72 hours when untreated or treated unsuccessfully and migraine episodes separated by at least 48 hours of headache pain freedom.
11. History of 2 to 8 migraine attacks per month with moderate to severe headache pain in each of the 3 months prior to Visit 1/Screening per investigator judgment.
12. Female subjects who are not pregnant or breastfeeding, and are not planning to become pregnant or donate eggs during the study and for approximately 30 days after the last dose of study drug.
13. Female subjects (or individuals) of childbearing potential must have a negative serum pregnancy test at Visit 1/Screening and a negative urine pregnancy test at Visit 2/Randomization. Subjects with a borderline serum pregnancy test at Visit 1/Screening must have absence of clinical suspicion of pregnancy or other pathological causes of borderline results and a serum pregnancy test ≥3 days later to document continued lack of a positive result (unless prohibited by local requirements). Subjects with a urine pregnancy test at Visit 2/Randomization that is borderline or ambiguous must have a serum pregnancy test. In such cases, the subjects must be excluded from participation if the serum pregnancy result is positive.

Exclusion criteria 31

1. Subject has difficulty in distinguishing migraine headache from tension-type or other headaches per the investigator's judgment.
2. History of an average of 15 or more headache days per month in the 6 months prior to Visit 1/Screening per the investigator's judgment, or a current diagnosis of chronic migraine as defined by ICHD-3. (Note: subjects with a diagnosis of chronic migraine who, in the opinion of the investigator, have fewer than 15 headache days per month due to concomitant prophylactic treatment are allowed to participate in the study).
3. Current diagnosis of new persistent daily headache, trigeminal autonomic cephalalgia (e.g., cluster headache), and painful cranial neuropathy as defined by ICHD-3.
4. Subject required hospital/emergency room treatment for migraine attacks on 3 or more occasions within 6 months prior to Visit 1/Screening.
5. ECG with clinically significant abnormalities at Visit 1/Screening, as determined by the investigator.
6. QTcF > 450 msec for males or QTcF > 470 msec for females at Visit 1/Screening based on the report of the central reviewer.
7. Hypertension defined as sitting systolic blood pressure > 160 mm Hg or sitting diastolic blood pressure > 100 mm Hg at Visit 1/Screening or Visit 2/Randomization. Blood pressure measurements that exceed these limits may be repeated only once.
8. Clinically significant abnormalities in the physical examination as determined by the investigator.
9. Clinically significant laboratory abnormalities as determined by the investigator, or laboratory values meeting any of the following criteria at Visit 1/Screening: ALT or AST > 1 × ULN; Total bilirubin > 1 × ULN (except for subjects with a diagnosis of Gilbert's disease); Serum albumin < 2.8 g/dL [4.06 µmol/L]
10. Positive result on the urine drug screen at Visit 1/Screening unless explained by allowed concomitant medication use (e.g., opioids prescribed for migraine pain, use of benzodiazepines for insomnia).
11. Positive result on the hepatitis B surface antigen or the anti-hepatitis C antibody testing at Visit 1/Screening.
12. Presence of other confounding pain syndromes, confounding psychiatric conditions, dementia, epilepsy and other significant neurological disorders other than migraine per investigator judgment.
13. Presence of chronic, nonheadache pain condition requiring daily pain medication.
14. Clinically significant cardiovascular, cerebrovascular, hematologic, endocrine, pulmonary, renal, hepatic, gastrointestinal, psychiatric, or neurologic disease. -If there is a history of such disease but the condition has been stable for more than 6 months prior to Visit 1/Screening and is judged by the investigator as not likely to interfere with the subject's participation in the study, the subject may be included. -Subjects on dialysis for renal failure are not allowed to participate in the study.
15. Significant risk of self-harm, based on clinical interview or responses on the C-SSRS, or harm to others per the opinion of the investigator; subjects must be excluded if they report suicidal ideation with intent, with or without a plan (i.e., Type 4 or 5 on the C-SSRS) in the past 6 months or report suicidal behavior in the last 6 months prior to Visit 1/Screening or Visit 2/Randomization.
16. History of malignancy in the 5 years prior to Visit 1/Screening, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer.
17. History of any prior gastrointestinal conditions (e.g., diarrhea syndromes, inflammatory bowel disease) that may affect the absorption or metabolism of study drug. -Subjects with prior gastric bariatric interventions (e.g., Lap Band) which have been reversed may participate.
18. History of acute hepatitis within 6 months of Visit 1/Screening or any history of chronic liver disease (including nonalcoholic fatty liver disease, viral chronic hepatitis, and cirrhosis).
19. History of hypersensitivity or clinically significant adverse reaction to a CGRP receptor antagonist.
20. Subject is an employee or immediate family member (parents, spouses, siblings, or children) of one of the investigators, study staff, or AbbVie.
21. Subject has condition or situation, which the investigator feels will compromise the safety of the subject or the quality of the data and renders the subject an unsuitable candidate for the study.
22. Subject has taken medication for acute treatment of headache (including acetaminophen, NSAIDs, triptans, ditans, ergotamine, opioids, gepants, or combination analgesics) 10 or more days per month in any of the 3 months prior to Visit 2/Randomization.
23. Subject has taken strong CYP3A4 inhibitors, including but not limited to systemic (oral/IV) itraconazole, ketoconazole, clarithromycin, telithromycin, nefazodone, and HIV protease inhibitors within 30 days or 5 half-lives of the drug (whichever is longer) prior to Visit 2/Randomization.
24. Subject has taken strong or moderate CYP3A4 inducers, including but not limited to barbiturates (e.g., phenobarbital and primidone), efavirenz, carbamazepine, phenytoin, rifampin, and St John's wort within 30 days or 5 half-lives of the drug (whichever is longer) prior to Visit 2/Randomization.
25. Subject has taken strong OATP1B1/OATP1B3 inhibitors (e.g., cyclosporine, telmisartan) within 30 days or 5 half-lives (whichever is longer) of the drug prior to Visit 2/Randomization.
26. Subject has taken drugs with narrow therapeutic margins with theoretical potential for CYP drug interactions (e.g., warfarin) within 30 days or 5 half-lives (whichever is longer) of the drug prior to Visit 2/Randomization.
27. Subject has been exposed to any gepant within 30 days prior to Visit 2/Randomization.
28. Subject has been exposed to injectable monoclonal antibodies blocking the CGRP pathway within 6 months prior to Visit 2/Randomization.
29. History of clinically significant drug or alcohol abuse or dependency in the 12 months prior to Visit 1/Screening, or subject had concomitant cannabis or ingested CBD oil use, either recreational or for medical reasons, within 30 days prior to Visit 2/Randomization.
30. Subject has been treated with any investigational drug within 30 days or 5 half-lives of the drug (whichever is longer) prior to Visit 2/Randomization or is currently enrolled in another clinical study or was previously enrolled in this study.
31. Subject has been treated with oral herbal medicine including, but not limited to, traditional Chinese medicine within 30 days or 5 half-lives (whichever is longer) prior to Visit 2/Randomization.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Pain freedom (defined as a reduction in headache severity from moderate/severe at baseline [predose] to no pain) at 2 hours after the DB dose for the first attack

Secondary endpoints 16

1. Absence of the MBS at 2 hours after the DB dose for the first attack (coprimary endpoint for China)
2. Pain relief (defined as the reduction of a moderate/severe migraine headache at baseline [predose] to a mild headache or to no headache) at 2 hours after the DB dose for the first attack
3. Sustained pain relief from 2 to 24 hours (defined as pain relief at 2 hours after the DB dose with no administration of rescue medication and no occurrence of a moderate/severe headache from 2 to 24 hours) after the DB dose for the first attack
4. Sustained pain relief from 2 to 48 hours after the DB dose for the first attack
5. Use of rescue medication within 24 hours after the DB dose for the first attack
6. Ability to function normally at 2 hours after the DB dose for the first attack
7. Sustained pain freedom from 2 to 24 hours (defined as pain freedom at 2 hours after the DB dose with no administration of rescue medication and no occurrence of a mild/moderate/severe headache from 2 to 24 hours) after the DB dose for the first attack
8. Sustained pain freedom from 2 to 48 hours after the DB dose for the first attack
9. Absence of photophobia at 2 hours after the DB dose for the first attack
10. Absence of phonophobia at 2 hours after the DB dose for the first attack
11. Pain freedom at 8 hours after the DB dose for the first attack
12. Ability to function normally 8 hours after the DB dose for the first attack
13. Pain relief at 1 hour after the DB dose for the first attack
14. Absence of nausea at 2 hours after the DB dose for the first attack
15. Pain relief at 30 minutes after the DB dose for the first attack
16. Ability to function normally at 1 hour after the DB dose for the first attack

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AbbVie Deutschland GmbH & Co. KG

Sponsor organisation

AbbVie Deutschland GmbH & Co. KG

Address

Knollstrasse

City

Ludwigshafen Am Rhein

Postcode

67061

Country

Germany

Scientific contact point

Organisation

AbbVie Deutschland GmbH & Co. KG

Contact name

Global Clinical Trials Helpdesk

Public contact point

Organisation

AbbVie Deutschland GmbH & Co. KG

Contact name

Global Clinical Trials Helpdesk

Third parties 10

Locations

10 EU/EEA countries · 75 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 144 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

18 submissions — initial application plus substantial / non-substantial modifications