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

• Sponsor: H. Lundbeck A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04152083
• Collaborator: Alder Biopharmaceuticals, Inc. (Industry)
• Enrollment: 485
• Locations: 57
• Arms: 2
• Actual Duration (Months): 8
• Patients Per Site: 8.5
• Patients Per Site Per Month: 1.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Migraine	Drug: Eptinezumab; Drug: Placebo	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 485 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Parallel Group, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Eptinezumab Administered Intravenously in Subjects Experiencing an Acute Attack of Migraine
• Actual Study Start Date: Nov 7, 2019
• Actual Primary Completion Date: Jul 8, 2020
• Actual Study Completion Date: Jul 8, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Eptinezumab Participants will receive a single dose of eptinezumab 100 milligrams (mg) administered via intravenous (IV) infusion on Day 0.	Drug: Eptinezumab; Injection for IV administration
Placebo Comparator: Placebo Participants will receive a single dose of placebo matching to eptinezumab administered via IV infusion on Day 0.	Drug: Placebo; Injection for IV administration

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alabama Clinical Therapeutics	Birmingham	Alabama	United States	35235
2	Arizona Research Center	Phoenix	Arizona	United States	85053
3	Baptist Health Center for Clinical Research	Little Rock	Arkansas	United States	72205
4	Advanced Research Center	Anaheim	California	United States	92805
5	The Neurology Center of Southern California - Carlsbad	Carlsbad	California	United States	92011
6	Excell research Inc	Oceanside	California	United States	92056
7	Anderson Clinical Research	Redlands	California	United States	92374
8	University of Colorado Hospital	Aurora	Colorado	United States	80045
9	Denver Neurological Clinic - Denver	Denver	Colorado	United States	80210
10	Coastal Connecticut Research LLC	New London	Connecticut	United States	06320
11	Ki Health Partners LLC, dba New England Institute for Clinical Research	Stamford	Connecticut	United States	06905
12	The George Washington Medical Faculty Associates	Washington	District of Columbia	United States	20052
13	Medicinae Doctor Clinical	Hallandale Beach	Florida	United States	33009
14	AGA Clinical trials	Hialeah	Florida	United States	33012
15	Meridien Research - Maitland	Maitland	Florida	United States	32751
16	Palm Beach Neurology and Premiere Research Institute	West Palm Beach	Florida	United States	33407
17	Clinical Research of Central Florida	Winter Haven	Florida	United States	33880
18	Office of Doctor Frank Berenson	Atlanta	Georgia	United States	30328
19	iResearch Atlanta, LLC	Decatur	Georgia	United States	30030
20	Meridian Clinical Research - Savannah Neurology Specialists	Savannah	Georgia	United States	31405
21	Cedar Crosse Research Center	Chicago	Illinois	United States	60607
22	College Park Family Care Center Physicians	Overland Park	Kansas	United States	66212
23	Phoenix Medical Research	Prairie Village	Kansas	United States	66208
24	Central Kentucky Research Associates	Lexington	Kentucky	United States	40509
25	Boston Clinical Trials	Boston	Massachusetts	United States	02131
26	MedVadis Research Corporation, LLC	Waltham	Massachusetts	United States	02451
27	Michigan Head Pain and Neurological institute	Ann Arbor	Michigan	United States	48104
28	Clinical Research Institute - Minneapolis	Minneapolis	Minnesota	United States	55402
29	Headache Neurology Research Institute	Ridgeland	Mississippi	United States	39157
30	StudyMetrix Research	Saint Peters	Missouri	United States	63303
31	Clinvest Research	Springfield	Missouri	United States	65810
32	Nevada Headache Institute	Las Vegas	Nevada	United States	89113
33	Albuqerque Clinical Trials	Albuquerque	New Mexico	United States	87102
34	Dent Neurologic Institute - Amherst	Amherst	New York	United States	14226
35	Integrative Clinical Trials	Brooklyn	New York	United States	11229
36	CTI Clinical Research center	Cincinnati	Ohio	United States	45212
37	Aventiv Research - Columbus	Columbus	Ohio	United States	43213
38	Hometown Urgent Care And Research - Huber Heights	Dayton	Ohio	United States	45424
39	Neuro-Behavioral Clinical Research Inc	North Canton	Ohio	United States	44720
40	Delricht Research	Tulsa	Oklahoma	United States	74133
41	Summit Research Network	Portland	Oregon	United States	97210
42	Frontier Clinical Rsearch LLC	Smithfield	Pennsylvania	United States	15478
43	Coastal Carolina Research Center - Mount Pleasant	Mount Pleasant	South Carolina	United States	29464
44	Chattanooga Medical research LLC	Chattanooga	Tennessee	United States	37404
45	WR-ClinSearch LLC	Chattanooga	Tennessee	United States	37421
46	Holston Medical Group - Kingsport	Kingsport	Tennessee	United States	37660
47	Ventavia Research Group, LLC	Fort Worth	Texas	United States	76104
48	Texas Center for Drug Development Inc	Houston	Texas	United States	77081
49	Ventavia Research Group, LLC	Keller	Texas	United States	76248
50	J. Lewis Research, Inc. / Foothill Family Clinic	Salt Lake City	Utah	United States	84109
51	Northwest Clinical Research Center	Bellevue	Washington	United States	98007
52	Neuroscience Group	Neenah	Wisconsin	United States	54956
53	Ltd "Acad Fridon Todua Medical Center - Ltd Research Institute of Clinical Medicine"	Tbilisi		Georgia
54	Ltd "Aversi Clinic"	Tbilisi		Georgia
55	Ltd "Multiprofile Clinica Consilium Medulla"	Tbilisi		Georgia
56	Ltd Simon Khechinashvili University Clinic	Tbilisi		Georgia
57	td "Israel-Georgia Medical Research Clinic Helsicore"	Tbilisi		Georgia

Sponsors and Collaborators

• H. Lundbeck A/S
• Alder Biopharmaceuticals, Inc.

Investigators

• Study Director: Email contact via H. Lundbeck A/S, [e-mail]

Study Documents (Full-Text)

• Study Protocol - Jul 1, 2020
• Statistical Analysis Plan - Aug 4, 2020

More Information

Publications

None provided.

• Responsible Party: H. Lundbeck A/S
• ClinicalTrials.gov Identifier: NCT04152083
• Other Study ID Numbers: ALD403-CLIN-015; 18903A
• First Posted: Nov 5, 2019
• Last Update Posted: Aug 17, 2021
• Last Verified: Aug 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Migraine Disorders

Study Results

Participant Flow

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

Arm/Group Title	Eptinezumab	Placebo
Arm/Group Description	Participants received a single dose of eptinezumab 100 mg administered via intravenous (IV) infusion on Day 0.	Participants received a single dose of placebo matched to eptinezumab administered via IV infusion on Day 0.
Period Title: Overall Study
STARTED	241	244
Received at Least 1 Dose of Study Drug	238	242
COMPLETED	235	241
NOT COMPLETED	6	3

Baseline Characteristics

Arm/Group Title	Eptinezumab	Placebo	Total
Arm/Group Description	Participants received a single dose of eptinezumab 100 mg administered via IV infusion on Day 0.	Participants received a single dose of placebo matched to eptinezumab administered via IV infusion on Day 0.	Total of all reporting groups
Overall Participants	238	242	480
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.9 (11.99)	44.1 (12.12)	44.5 (12.05)
Sex: Female, Male (Count of Participants)
Female	202 84.9%	201 83.1%	403 84%
Male	36 15.1%	41 16.9%	77 16%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	29 12.2%	31 12.8%	60 12.5%
Not Hispanic or Latino	209 87.8%	211 87.2%	420 87.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
White	200 84%	213 88%	413 86%
Black or African American	30 12.6%	19 7.9%	49 10.2%
Asian	2 0.8%	3 1.2%	5 1%
American Indian or Alaska Native	2 0.8%	1 0.4%	3 0.6%
Native Hawaiian or other Pacific Islander	1 0.4%	1 0.4%	2 0.4%
Other	0 0%	1 0.4%	1 0.2%
Multiple	3 1.3%	4 1.7%	7 1.5%
Number of Migraine Days/Month (days/month) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [days/month]	7.2 (2.65)	7.2 (2.56)	7.2 (2.60)
Number of Participants With Most Bothersome Symptoms (MBS) (participants) [Number]
Photophobia	114 47.9%	114 47.1%	228 47.5%
Nausea	78 32.8%	79 32.6%	157 32.7%
Phonophobia	46 19.3%	47 19.4%	93 19.4%
Missing	0 0%	2 0.8%	2 0.4%

Outcome Measures

1. Primary Outcome

Title	Time to Headache Pain Freedom
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Eptinezumab	Placebo
Arm/Group Description	Participants received a single dose of eptinezumab 100 mg administered via IV infusion on Day 0.	Participants received a single dose of placebo matched to eptinezumab administered via IV infusion on Day 0.
Measure Participants	238	242
Median (Inter-Quartile Range) [hours]	4.0	9.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eptinezumab, Placebo
	Comments	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.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0006
	Comments	Threshold for significance at 0.05 level.
	Method	Likelihood ratio test
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.54
	Confidence Interval	(2-Sided) 95%; 1.20 to 1.98
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Time to Absence of Most Bothersome Symptom (MBS)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Eptinezumab	Placebo
Arm/Group Description	Participants received a single dose of eptinezumab 100 mg administered via IV infusion on Day 0.	Participants received a single dose of placebo matched to eptinezumab administered via IV infusion on Day 0.
Measure Participants	238	240
Median (Inter-Quartile Range) [hours]	2.0	3.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eptinezumab, Placebo
	Comments	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.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance at 0.05 level.
	Method	Likelihood ratio test
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.75
	Confidence Interval	(2-Sided) 95%; 1.41 to 2.19
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Headache Pain Freedom at 2 Hours
Description	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

Outcome Measure Data

Analysis Population Description

FAP included all randomized participants who received eptinezumab or placebo.

Arm/Group Title	Eptinezumab	Placebo
Arm/Group Description	Participants received a single dose of eptinezumab 100 mg administered via IV infusion on Day 0.	Participants received a single dose of placebo matched to eptinezumab administered via IV infusion on Day 0.
Measure Participants	238	242
Count of Participants [Participants]	56 23.5%	29 12%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eptinezumab, Placebo
	Comments	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.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0009
	Comments	Threshold for significance at 0.05 level.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.27
	Confidence Interval	(2-Sided) 95%; 1.39 to 3.72
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Absence of MBS at 2 Hours
Description	Number of participants with absence of MBS (of nausea, photophobia, or phonophobia) at 2 hours postdose are reported.
Time Frame	2 hours

Outcome Measure Data

Analysis Population Description

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/Group Title	Eptinezumab	Placebo
Arm/Group Description	Participants received a single dose of eptinezumab 100 mg administered via IV infusion on Day 0.	Participants received a single dose of placebo matched to eptinezumab administered via IV infusion on Day 0.
Measure Participants	238	240
Count of Participants [Participants]	132 55.5%	86 35.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eptinezumab, Placebo
	Comments	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.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance at 0.05 level.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.25
	Confidence Interval	(2-Sided) 95%; 1.55 to 3.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Headache Pain Freedom at 4 Hours
Description	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

Outcome Measure Data

Analysis Population Description

FAP included all randomized participants who received eptinezumab or placebo.

Arm/Group Title	Eptinezumab	Placebo
Arm/Group Description	Participants received a single dose of eptinezumab 100 mg administered via IV infusion on Day 0.	Participants received a single dose of placebo matched to eptinezumab administered via IV infusion on Day 0.
Measure Participants	238	242
Count of Participants [Participants]	111 46.6%	64 26.4%

6. Secondary Outcome

Title	Absence of MBS at 4 Hours
Description	Number of participants with absence of MBS (of nausea, photophobia, or phonophobia) at 4 hours postdose are reported.
Time Frame	4 hours

Outcome Measure Data

Analysis Population Description

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/Group Title	Eptinezumab	Placebo
Arm/Group Description	Participants received a single dose of eptinezumab 100 mg administered via IV infusion on Day 0.	Participants received a single dose of placebo matched to eptinezumab administered via IV infusion on Day 0.
Measure Participants	238	240
Count of Participants [Participants]	155 65.1%	90 37.2%

7. Secondary Outcome

Title	Use of Rescue Medication Within the First 24 Hours
Description	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

Outcome Measure Data

Analysis Population Description

FAP included all randomized participants who received eptinezumab or placebo.

Arm/Group Title	Eptinezumab	Placebo
Arm/Group Description	Participants received a single dose of eptinezumab 100 mg administered via IV infusion on Day 0.	Participants received a single dose of placebo matched to eptinezumab administered via IV infusion on Day 0.
Measure Participants	238	242
Count of Participants [Participants]	75 31.5%	145 59.9%

Adverse Events

Time Frame	Start of treatment (Day 0) through end of study (Week 4)
Adverse Event Reporting Description	Safety population included all participants who received eptinezumab or placebo.
Arm/Group Title	Eptinezumab		Placebo
Arm/Group Description	Participants received a single dose of eptinezumab 100 mg administered via IV infusion on Day 0.		Participants received a single dose of placebo matched to eptinezumab administered via IV infusion on Day 0.
All Cause Mortality
	Eptinezumab		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/238 (0%)		0/242 (0%)
Serious Adverse Events
	Eptinezumab		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/238 (0%)		0/242 (0%)
Other (Not Including Serious) Adverse Events
	Eptinezumab		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/238 (2.1%)		0/242 (0%)
Immune system disorders
Hypersensitivity	5/238 (2.1%)	5	0/242 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.