A Study to Evaluate the Efficacy and Safety of Eptinezumab Administered Intravenously in Participants Experiencing Acute Attack of Migraine

Conditions

Migraine

Brief summary

The purpose of this study is to evaluate the efficacy and safety of eptinezumab administered intravenously in participants experiencing an acute attack of migraine.

Detailed description

This will be a parallel group, double-blind, randomized, placebo-controlled study assessing the efficacy of eptinezumab for acute migraine, defined as an active intercurrent migraine occurring in those participants who are candidates for preventive therapy. Participants will be randomized to receive a single dose of eptinezumab or placebo in a 1:1 ratio. The total study duration will be approximately 4 to 12 weeks, including up to an 8-week screening period and 4-week of safety follow-up, with clinic visits occurring on Screening, Day 0 (dosing day), and Week 4.

Roger Cady, Richard B. Lipton, Dawn C. Buse, Mette Krog Josiassen, Annika Lindstén et al. (6 authors)

The Journal of Headache and Pain2022-07-288 citations

10.1186/s10194-022-01463-3

Rapid resolution of migraine symptoms after initiating the preventive treatment eptinezumab during a migraine attack: results from the randomized RELIEF trial

Jessica Ailani, Peter McAllister, Paul Winner, George Chakhava, Mette Krog Josiassen et al. (9 authors)

BMC Neurology2022-06-0320 citations

10.1186/s12883-022-02714-1

P.017 Optimization of acute treatment and headache-related impact following eptinezumab initiated during a migraine attack: post hoc analysis of the RELIEF study

DC Buse, RB Lipton, A Ettrup, MK Josiassen, A Lindsten et al. (8 authors)

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques2022-06-01

10.1017/cjn.2022.120

Eptinezumab treatment initiated during a migraine attack is associated with meaningful improvement in patient-reported outcome measures: secondary results from the randomized controlled RELIEF study.

McAllister P, Winner PK, Ailani J, Buse DC, Lipton RB, Chakhava G, Josiassen MK, Lindsten A, Mehta L, Ettrup A, Cady R.

2022-02-079 citations

10.1186/s10194-021-01376-7

P.027 Efficacy and Safety of Eptinezumab Initiated During a Migraine Attack: Results from the RELIEF Study

P. K. Winner, Peter McAllister, George Chakhava, Jessica Ailani, Lahar Mehta et al. (10 authors)

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques2021-11-011 citations

10.1017/cjn.2021.309

Effects of Intravenous Eptinezumab vs Placebo on Headache Pain and Most Bothersome Symptom When Initiated During a Migraine Attack

Paul Winner, Peter McAllister, George Chakhava, Jessica Ailani, Anders Ettrup et al. (9 authors)

JAMA2021-06-1596 citations

10.1001/jama.2021.7665

Antibodies to watch in 2020.

Kaplon H, Muralidharan M, Schneider Z, Reichert JM.

2020-01-01328 citations

10.1080/19420862.2019.1703531

Interventions

DRUGEptinezumab

Injection for IV administration

DRUGPlacebo

Injection for IV administration

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

No

Inclusion criteria

* Greater than 1-year history of migraine, with or without aura, with onset of first migraine before age 50. * Migraine on 4 to 15 days per month in the 3 months prior to screening. * Headache free for at least 24 hours prior to onset of a qualifying migraine.

Exclusion criteria

* Unable to differentiate migraine from other headache or pain disorders. * Use of the following medication, for any indication, within the 24-hour period prior to dosing with study drug: 1. triptans, ergotamines and ergot-derivatives 2. analgesics (including but not limited to acetaminophen, tramadol, nonsteroidal anti-inflammatory drugs \[NSAIDs\], combination analgesics, caffeine-containing analgesics, and opioids/narcotics) and other acute migraine medication(s) 3. antiemetic medications (including but not limited to prochlorperazine, promethazine, droperidol, chlorpromazine, metoclopramide) 4. antihistamines 5. devices, neuromodulation, neurostimulation, or injectable therapy (trigger point injections, extracranial nerve blocks, facet joint injections, spinal manipulation) * Use of the following medication, for any indication, in each of the 3 months prior to screening: 1. opioids/narcotics or butalbital containing products (including combinations) on more than 4 days per month; 2. triptans, ergotamines, or combination analgesics for 10 or more days per month; 3. acetaminophen, aspirin or NSAIDs for 15 or more days per month (except if participant is taking 81 mg dose of aspirin for cardiac prophylaxis) * History or diagnosis of chronic tension-type headache, hypnic headache, cluster headache, hemicrania continua, new daily persistent headache, or unusual migraine subtypes such as hemiplegic migraine (sporadic and familial), ophthalmoplegic migraine and migraine with neurological accompaniments that are not typical of migraine aura (for example, diplopia, altered consciousness, or long duration). * Any changes to preventive migraine treatment(s) within 1 month prior to screening and up to treatment with the study drug (Day 0). * Any use of approved devices, neuromodulation, neurostimulation, or injectable therapy (trigger point injections, extracranial nerve blocks, facet joint injections) within the 24-hour period prior to treatment with study drug (Day 0). * Any use of botulinum toxin for migraine or for any other medical/cosmetic reasons requiring injections within 7 days prior to treatment with study drug (Day 0). * Any use of systemic corticosteroid for migraine or any other reason within 3 months prior to treatment with study drug (Day 0). * Evidence or medical history of clinically significant psychiatric diseases that are uncontrolled and/or untreated. * Receipt of any monoclonal antibody treatment, for migraine or any other indication, (within or outside a clinical study) within 6 months prior to screening.

Design outcomes

Primary

Measure	Time frame	Description
Time to Headache Pain Freedom	Up to 48 hours postdose	Time to headache pain freedom defined as the time that the participant reported freedom of pain, meaning their headache pain had gone from moderate to severe at baseline to no pain.
Time to Absence of Most Bothersome Symptom (MBS)	Up to 48 hours postdose	Time to absence of most bothersome symptom defined as the time that the participant reported absence of MBS (of nausea, photophobia, or phonophobia).

Secondary

Measure	Time frame	Description
Headache Pain Freedom at 2 Hours	2 hours	Number of participants with freedom from headache pain at 2 hours postdose are reported. Freedom from headache pain meaning that the headache pain that had gone from moderate to severe at baseline to no pain with no administration of rescue medications.
Absence of MBS at 2 Hours	2 hours	Number of participants with absence of MBS (of nausea, photophobia, or phonophobia) at 2 hours postdose are reported.
Headache Pain Freedom at 4 Hours	4 hours	Number of participants with freedom from headache pain at 4 hours postdose are reported. Freedom from headache pain meaning that the headache pain that had gone from moderate to severe at baseline to no pain with no administration of rescue medications.
Absence of MBS at 4 Hours	4 hours	Number of participants with absence of MBS (of nausea, photophobia, or phonophobia) at 4 hours postdose are reported.
Use of Rescue Medication Within the First 24 Hours	Up to 24 hours postdose	Rescue medication was defined as any medication to treat migraine or migraine-associated symptoms, which could have been provided to the participant any time after 2 hours post-start of infusion. Use of rescue medication was captured in the eDiary. Number of participants who used rescue medication up to 24 hours postdose are reported.

Countries

Georgia, United States

Participant flow

Pre-assignment details

Participants were randomized to receive either 100 milligrams (mg) eptinezumab or placebo in a 1:1 ratio.

Participants by arm

Arm	Count
Eptinezumab Participants received a single dose of eptinezumab 100 mg administered via IV infusion on Day 0.	238
Placebo Participants received a single dose of placebo matched to eptinezumab administered via IV infusion on Day 0.	242
Total	480

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	1	0
Overall Study	Lost to Follow-up	2	1
Overall Study	Randomized but not treated	3	2

Baseline characteristics

Characteristic	Eptinezumab	Total	Placebo
Age, Continuous	44.9 years STANDARD_DEVIATION 11.99	44.5 years STANDARD_DEVIATION 12.05	44.1 years STANDARD_DEVIATION 12.12
Ethnicity (NIH/OMB) Hispanic or Latino	29 Participants	60 Participants	31 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	209 Participants	420 Participants	211 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Number of Migraine Days/Month	7.2 days/month STANDARD_DEVIATION 2.65	7.2 days/month STANDARD_DEVIATION 2.6	7.2 days/month STANDARD_DEVIATION 2.56
Number of Participants With Most Bothersome Symptoms (MBS) Missing	0 participants	2 participants	2 participants
Number of Participants With Most Bothersome Symptoms (MBS) Nausea	78 participants	157 participants	79 participants
Number of Participants With Most Bothersome Symptoms (MBS) Phonophobia	46 participants	93 participants	47 participants
Number of Participants With Most Bothersome Symptoms (MBS) Photophobia	114 participants	228 participants	114 participants
Race/Ethnicity, Customized Race American Indian or Alaska Native	2 Participants	3 Participants	1 Participants
Race/Ethnicity, Customized Race Asian	2 Participants	5 Participants	3 Participants
Race/Ethnicity, Customized Race Black or African American	30 Participants	49 Participants	19 Participants
Race/Ethnicity, Customized Race Multiple	3 Participants	7 Participants	4 Participants
Race/Ethnicity, Customized Race Native Hawaiian or other Pacific Islander	1 Participants	2 Participants	1 Participants
Race/Ethnicity, Customized Race Other	0 Participants	1 Participants	1 Participants
Race/Ethnicity, Customized Race White	200 Participants	413 Participants	213 Participants
Sex: Female, Male Female	202 Participants	403 Participants	201 Participants
Sex: Female, Male Male	36 Participants	77 Participants	41 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 238	0 / 242
other Total, other adverse events	5 / 238	0 / 242
serious Total, serious adverse events	0 / 238	0 / 242

Outcome results

Primary

Time to Absence of Most Bothersome Symptom (MBS)

Time to absence of most bothersome symptom defined as the time that the participant reported absence of MBS (of nausea, photophobia, or phonophobia).

Time frame: Up to 48 hours postdose

Population: FAP included all randomized participants who received eptinezumab or placebo. Here, 'Overall number of participants analyzed' signifies participants with both baseline and post-baseline data (the symptom that was most bothersome).

Arm	Measure	Value (MEDIAN)
Eptinezumab	Time to Absence of Most Bothersome Symptom (MBS)	2.0 hours
Placebo	Time to Absence of Most Bothersome Symptom (MBS)	3.0 hours

Comparison: The median estimate for each treatment group, hazard ratio, and its 95% CI were based on the stratified Cox model with Efron's method of tie handling. The analysis was censored at the time point of first rescue medication. The stratification factors were concomitant migraine preventive treatment use and region.p-value: <0.000195% CI: [1.41, 2.19]Likelihood ratio test

Primary

Time to Headache Pain Freedom

Time to headache pain freedom defined as the time that the participant reported freedom of pain, meaning their headache pain had gone from moderate to severe at baseline to no pain.

Time frame: Up to 48 hours postdose

Population: Full analysis population (FAP) included all randomized participants who received eptinezumab or placebo.

Arm	Measure	Value (MEDIAN)
Eptinezumab	Time to Headache Pain Freedom	4.0 hours
Placebo	Time to Headache Pain Freedom	9.0 hours

Comparison: The median estimate for each treatment group, hazard ratio, and its 95% confidence interval (CI) were based on the stratified Cox model with Efron's method of tie handling. The analysis was censored at the time point of first rescue medication. The stratification factors were concomitant migraine preventive treatment use and region.p-value: 0.000695% CI: [1.2, 1.98]Likelihood ratio test

Secondary

Absence of MBS at 2 Hours

Number of participants with absence of MBS (of nausea, photophobia, or phonophobia) at 2 hours postdose are reported.

Time frame: 2 hours

Population: FAP included all randomized participants who received eptinezumab or placebo. Here, 'Overall number of participants analyzed' signifies participants with both baseline and post-baseline data (the symptom that was most bothersome).

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Eptinezumab	Absence of MBS at 2 Hours	132 Participants
Placebo	Absence of MBS at 2 Hours	86 Participants

Comparison: Odds ratio and 95% CI were based on CMH test adjusted for the study's stratification factors of concomitant migraine preventive treatment use and region.p-value: <0.000195% CI: [1.55, 3.25]Cochran-Mantel-Haenszel

Secondary

Absence of MBS at 4 Hours

Number of participants with absence of MBS (of nausea, photophobia, or phonophobia) at 4 hours postdose are reported.

Time frame: 4 hours

Population: FAP included all randomized participants who received eptinezumab or placebo. Here, 'Overall number of participants analyzed' signifies participants with both baseline and post-baseline data (the symptom that was most bothersome).

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Eptinezumab	Absence of MBS at 4 Hours	155 Participants
Placebo	Absence of MBS at 4 Hours	90 Participants

Secondary

Headache Pain Freedom at 2 Hours

Number of participants with freedom from headache pain at 2 hours postdose are reported. Freedom from headache pain meaning that the headache pain that had gone from moderate to severe at baseline to no pain with no administration of rescue medications.

Time frame: 2 hours

Population: FAP included all randomized participants who received eptinezumab or placebo.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Eptinezumab	Headache Pain Freedom at 2 Hours	56 Participants
Placebo	Headache Pain Freedom at 2 Hours	29 Participants

Comparison: Odds ratio and 95% CI were based on Cochran-Mantel-Haenszel (CMH) test adjusted for the study's stratification factors of concomitant migraine preventive treatment use and region.p-value: 0.000995% CI: [1.39, 3.72]Cochran-Mantel-Haenszel

Secondary

Headache Pain Freedom at 4 Hours

Number of participants with freedom from headache pain at 4 hours postdose are reported. Freedom from headache pain meaning that the headache pain that had gone from moderate to severe at baseline to no pain with no administration of rescue medications.

Time frame: 4 hours

Population: FAP included all randomized participants who received eptinezumab or placebo.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Eptinezumab	Headache Pain Freedom at 4 Hours	111 Participants
Placebo	Headache Pain Freedom at 4 Hours	64 Participants

Secondary

Use of Rescue Medication Within the First 24 Hours

Rescue medication was defined as any medication to treat migraine or migraine-associated symptoms, which could have been provided to the participant any time after 2 hours post-start of infusion. Use of rescue medication was captured in the eDiary. Number of participants who used rescue medication up to 24 hours postdose are reported.

Time frame: Up to 24 hours postdose

Population: FAP included all randomized participants who received eptinezumab or placebo.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Eptinezumab	Use of Rescue Medication Within the First 24 Hours	75 Participants
Placebo	Use of Rescue Medication Within the First 24 Hours	145 Participants

A Study to Evaluate the Efficacy and Safety of Eptinezumab Administered Intravenously in Participants Experiencing Acute Attack of Migraine

Conditions

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Time to Absence of Most Bothersome Symptom (MBS)

Time to Headache Pain Freedom

Absence of MBS at 2 Hours

Absence of MBS at 4 Hours

Headache Pain Freedom at 2 Hours

Headache Pain Freedom at 4 Hours

Use of Rescue Medication Within the First 24 Hours