A Study to Assess the Efficacy and Safety of Elismetrep (K-304) in the Acute Treatment of Migraine

ClinicalTrials.gov ID

NCT07816367

Lead Sponsor

Kallyope Inc.INDUSTRY

Overall Status

Not yet recruiting

Study Type

Interventional

Phase

Phase 3

Enrollment

1,500Estimated

Last Update Posted

Sep 11, 2026Actual

Start Date

Sep 2026Estimated

Primary Completion Date

Sep 2027Estimated

Completion Date

Dec 2027Estimated

Official Title

A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Elismetrep (K-304) in the Acute Treatment of Migraine

Brief Summary

This is a double-blind, randomized, multicenter, outpatient evaluation of the safety and efficacy of elismetrep, as compared with placebo, in the treatment of moderate or severe of migraine.

• Migraine

• Elismetrep
• Placebo

Ages Eligible for Study

Adult (18-64)Older Adult (65+)

Sexes Eligible for Study

All

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria:

1. Be a male or female, age 18 to 75 years, inclusive, at the time of signing informed consent.

2. Has greater than a one-year history of migraine with or without aura as defined by International Headache Society criteria 1.1 and 1.2 and his/her migraines typically last between 4 to 72 hours, if untreated as documented in the patient's medical records from his/her treating physician or with pharmacy records confirming use of a migraine-specific medication (e.g. triptan, gepant, ditan) for > 1 year, and confirmed by the investigator. 3. Has had ≥2 and ≤10 moderate or severe migraine attacks per month in each of the 2 months prior to screening (Visit 1). 4. Meet the following requirements:

a. Is a male OR b. Is a female who is of non-childbearing potential defined by at least one of the following criteria: i. Postmenopausal as defined by one of the following:

1. A minimum of 12 months of spontaneous amenorrhea or
2. A minimum of 6 months of spontaneous amenorrhea with a screening serum follicle-stimulating hormone level > 40 mIU/mL or
3. At least 6 weeks post bilateral oophorectomy (with or without hysterectomy). OR ii. Post hysterectomy or bilateral salpingectomy, based on the subject's recall of their medical history OR c. Is a female of reproductive potential and: i. Agrees to remain abstinent from heterosexual activity* OR ii. Agrees to use (or have their partner use) a birth control method that is acceptable from the first dose of study drug until the End of Study visit.

Acceptable methods of birth control are:

1. Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal).
2. Progestogen-only hormonal contraception associated with inhibition of ovulation (oral; injectable; or implantable).
3. Intrauterine device (IUD);
4. Intrauterine hormone-releasing system (IUS);
5. Bilateral tubal occlusion;
6. Vasectomized partner;
7. Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mode of action;
8. Male or female condom with or without spermicide;
9. Cap, diaphragm or sponge with spermicide;
10. A combination of male condom with either cap, diaphragm or sponge with spermicide (double barrier methods). * Abstinence can be used as the sole method of contraception if it is in line with the subject's preferred and usual lifestyle and if considered acceptable by local regulatory agencies and ethics committees. Periodic abstinence (e.g., calendar, ovulation, sympto-thermal, post-ovulation methods, etc.) and withdrawal are not acceptable methods of contraception.

5. Voluntarily agrees to participate in the study by giving written informed consent. 6. Is able to read, understand and complete the study questionnaires and eDiary. 7. Be willing and able to comply with the study schedule of visits, all trial procedures and restrictions. 8. Be willing to use their own personal, qualified smartphone to download study specific eDiary applications for use during the study.

Exclusion Criteria:

Patients are excluded from the trial if any of the following criteria apply:

1. Is a female who is pregnant, breast-feeding, or intends to become pregnant during the planned course of the study. Note: Female participants of child-bearing potential must have a negative serum pregnancy test (β-human chorionic gonadotropin) performed by the central laboratory prior to enrollment in the study and negative urine pregnancy result at the randomization visit.

   Migraine history-related

2. Has difficulty distinguishing his/her migraine attacks from tension-type headaches.

3. Has a history of predominantly mild migraine attacks or migraines that usually resolve spontaneously in less than 2 hours.

4. Has more than 15 headache-days per month or has taken medication for acute headache on more than 10 days per month in any of the 3 months prior to screening (Visit 1).

5. Has brainstem (also known as basilar-type) or hemiplegic migraine headache, or retinal migraine.

6. Was >50 years old at age of first migraine onset.

7. Is taking migraine prophylactic medication where the prescribed dose has changed during the 3 months prior to screening (Visit 1) or anticipates any change during the study. Any withdrawal of preventive medications for the treatment of migraine should be completed at least 30 days prior to screening.

   Medical history related

8. Has, in the opinion of the investigator, other confounding pain syndromes, psychiatric conditions such as uncontrolled major depression, history of psychosis, dementia, or significant neurological disorders other than migraine [Patients who are currently being treated with non-prohibited medication for depression and symptoms are well controlled, in the opinion of the investigator, are eligible to participate in this study].

9. Is at imminent risk of self-harm, based on clinical interview and responses on the Columbia Suicidality Severity Rating Scale (C-SSRS), or of harm to others in the opinion of the investigator. Patients 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 2 months or suicidal behavior in the past 6 months.

10. Has a recent history (within the past 3 years of the screening visit) or current diagnosis or evidence of endocrine, hematological, immunological (including Sjogren's syndrome), renal, respiratory, neurologic, gastrointestinal, biliary, or genitourinary abnormalities or diseases or hepatic impairment that, per the investigator's judgement, may jeopardize the subject's safety or compliance with the protocol, or otherwise interfere with interpretation of efficacy and/or safety results.

11. Has a history of malignant neoplasms within the past 5 years prior to screening. Basal and squamous cell skin cancer and any carcinoma in-situ are allowed if they have received treatment and follow-up consistent with local standard of care.

12. Has a history with current evidence of uncontrolled, unstable or recently diagnosed cardiovascular disease, such as ischemic heart disease, coronary artery vasospasm, and cerebral ischemia. Patients with myocardial infarction, acute coronary syndrome, percutaneous coronary intervention, cardiac surgery, stroke or transient ischemic attack during the 6 months prior to screening.

13. Has a history of human immunodeficiency virus disease.

14. Has a history of gastric or small intestinal surgery (including gastric bypass surgery or banding but not including cholecystectomy or appendectomy) or has a disease that causes malabsorption.

    Laboratory, vital sign, and electrocardiogram related

15. Has a positive test result at screening for hepatitis B surface antigen, hepatitis C virus antibody.

16. Has a screening estimated glomerular filtration rate estimated with the Modification of Diet in Renal Disease (MDRD) equation of <30 mL/min/1.73 m2.

17. Has a screening result for alanine aminotransferase or aspartate aminotransferase of >2.0 X upper limit of normal (ULN) or total bilirubin >1.5 X ULN at the Screening visit. Note: An isolated bilirubin >1.5 X ULN is acceptable if bilirubin is fractionated and direct bilirubin is within the laboratory normal range.

18. Has a mean value for triplicate corrected QT interval to Fridericia's formula (QTcF) >450 ms for males and >470 ms for females at screening.

19. Has a mean value for triplicate seated systolic blood pressure >160 mmHg and/or diastolic blood pressure >95 mmHg measured after at least 5 minutes at rest at the Screening Visit. Note: If a participant's blood pressure is exclusionary on the first triplicate assessment at the Screening Visit, they may have one repeat triplicate blood pressure assessment at that visit after another rest of at least 10 minutes.

    Medication use and substance abuse related

20. Has known history of or suspected abuse of alcohol or recreational drugs at Screening.

21. Has use of soft drugs (such as marijuana or any substances containing tetrahydrocannabinol (THC) or cannabidiol (CBD) within 3 months prior to screening, or hard drugs (such as cocaine, illicit narcotics/opiates) within 6 months prior to screening.

22. Has a positive drug screen at screening. Note:

    1. If benzodiazepines are detected on the drug screen, this is not exclusionary if they are prescribed a benzodiazepine for a therapeutic purpose (e.g., for insomnia) and confirmatory documentation is obtained from the prescribing physician.
    2. If amphetamines are detected on the drug screen, this is not exclusionary if the participant is taking a stimulant medication for a therapeutic purpose (e.g., Adderall for attention deficit hyperactivity disorder), confirmatory documentation is obtained from the prescribing physician, and the stimulant medication in question is known to be detected as amphetamine on the drug screen being used.

23. Is currently in violation of study requirements for prohibited and permissible concomitant medications or treatments (not already specified in other criteria) or is anticipated to violate these requirements during study participation (detailed in the protocol).

24. Has any use of prescription opiate medications within 14 days of screening or any anticipated/potential use of opiates during study participation.

25. Has a history of use of ergotamine medications ≥10 days per month on a regular basis for ≥3 months prior to screening.

26. Has a history of non-narcotic analgesic intake ≥15 days per month for ≥3 months prior to screening.

    Other

27. Has known or suspected hypersensitivity to trial product(s) or related products.

28. Has a history of multiple significant and/or any severe allergies (e.g., food, drug, latex allergy) or has had an anaphylactic reaction or significant intolerance to prescription or nonprescription drugs or food.

29. Has any surgery scheduled for the duration of the trial.

30. Has a screening hemoglobin <11.0 g/dL (males) or <10.0 g/dL (females) or has a known hemoglobinopathy (e.g., sickle cell anemia, hemolytic anemia).

31. Has previous participation in this trial. Participation is defined as signed informed consent.

32. Has participated in any clinical trial of an approved or non-approved investigational biological medicinal product (e.g., antibody therapy) within 90 days of screening or has participated in any clinical trial of an approved or non-approved investigational small molecule medicinal product within 30 days or 5 half-lives (whichever is longer) of screening or ever signed an informed consent for Study K-304 P003. Note: Patients may not be screened at more than one trial site for this study.

33. Has any other disorder, unwillingness or inability, not covered by any of the other exclusion criteria, which in the investigator's opinion, might jeopardize the subject's safety or compliance with the protocol, or otherwise interfere with interpretation of efficacy and/or safety results.

34. Is an employee or immediate family member (e.g., spouse, parent, child, sibling) of the Sponsor or study site. Note: Rescreening/retesting is not permitted unless specified above.

Primary Purpose

Treatment

Allocation

Randomized

Interventional Model

Parallel Assignment

Masking

Triple

Lead Sponsor

Kallyope Inc.INDUSTRY

cplimpton@velocityclinical.com602-368-1928

payam.sadr@imaresearch.com602-562-7000

pewyliemd1@outlook.com501-553-9987

admatian@allianceri.org818-835-9085

sovercash@velocityclinical.com619-955-5246

pi1241@interspond.com310-710-2985

drciabarra@gmail.com714-879-7200

morganwelebir@axiomresearch.com909-824-2335

sfussell@lbclinicaltrials.com562-997-3869

Ezrtrials@gmail.com562-492-9966

nglaze@allianceri.org818-835-9085

sfaqihi@northridgetrials.com818-350-7483

ttzao@pasadenatrials.com626-822-6554

sfinch@paradigm-research.com530-247-7049

jpandit@infinityclinicalstudies.com619-704-0808

gboone@paradigm-research.com858-274-4226

shassler@studyops.com415-518-1292

Kelvin.Mai@prxclinical.com714-617-5689

mturner@velocityclinical.com818-487-3741

nmoore@paradigm-research.com303-219-1830

ashackleford@centennialclinicaltrials.com650-995-4233

peter@neinh.com203-914-1900

bsafirstein@velocityclinical.com954-455-5757

jsmith@clinicalresearchcf.com1-863-853-5400

dr.latorre@applemedresearch.org305-667-8434

drtaylor@sensiblehealthcare.net407-654-2724

alizama@clinicalassociatesorlando.com407-269-0322

d.white@cenexel.com813-264-2155

fberenson@pandaneuro.com678-705-7341

dr.pelishev@evergreenstrials.com678-884-0550

pbradley@velocityclinical.com912-443-4253

jherrold@paradigm-research.com208-801-7440

lgonzalez@cisresearch.com847-599-2492

jgeohas@evanstonpremier.com847-869-1191

brandon.essink.ns@dmclinical.com463-271-3050

amalik@indianaclinicalresearch.com219-207-5053

jkillion@mcfarlandclinic.com515-956-4159

ensz@velocityclinical.com712-639-6300

esorial@neccr.com508-672-7450

snapoli@neurocenterne.com781-551-5812 ext. 142

ccone@montanamedicalresearch.com406-519-2132

charper@velocityclinical.com402-371-0797

bauer@qcrnetwork.com402-934-0044

stam@oasistrials.com702-832-1369

ap@bbhnj.com732-244-2299

sshoffner@carymedicalgroup.com919-342-3447

patrick.morgante@westclinicalresearch.com252-515-0050

Kevin.Cannon@accellacare.com910-799-5500

Mitchell.isaac2023@gmail.com336-768-8062

lillestolmd@lillestolresearch.com701-232-7705

mrhee@velocityclinical.com216-682-0320

aruksenas@velocityclinical.com513-769-2767

drobrien@hcohcincy.com513-898-9400

Sridhar.Guduri@centricityresearch.com614-501-6164

dfried@velocityclinical.com401-739-9350 ext. 2333

dwilliams3@velocityclinical.com864-965-0190

derb@velocityclinical.com864-488-1283

pi362@interspond.com512-480-9660

ksenthilkumar@gadolin.com409-331-6040

jbashour@velocityclinical.com682-348-1169

ppatel@epicmedresearch.com972-777-6954

md.amaspons@gmail.com915 598-8888

resnick.redstarresearch@gmail.com979-529-9440

dgordon@sanantoniotrials.com945-218-5593

irfan.lalani@dmclinical.com346-550-9559

drirfan@dmclinical.com281-517-0550

dlarsen@wasatchcrc.com801-288-0607

derekmuse@msn.com801-559-3855

• A Study to Evaluate the Efficacy and Safety of Elismetrep (K-304) in the Acute Treatment of Migraine

  NCT07645924

  RecruitingInterventionalPhase 3Updated Aug 20, 2026
• A Phase IIb, Randomized, Double-Blind, Placebo-Controlled Study of Elismetrep (K-304) in the Treatment of Migraine

  NCT06848075

  CompletedInterventionalPhase 2Updated Aug 27, 2026
• A Long-Term Safety Study of Elismetrep (K-304) in the Acute Treatment of Migraine

  NCT07674654

  RecruitingInterventionalPhase 3Updated Aug 27, 2026
• A Study of the Safety and Efficacy of MK-6096 for Migraine Prophylaxis in Participants With Episodic Migraine (MK-6096-020)

  NCT01513291

  CompletedInterventionalPhase 2Updated Nov 7, 2018
• Efficacy, Safety, and Tolerability of Oral Eletriptan for Treatment of Acute Migraine

  NCT01978496

  CompletedInterventionalPhase 3Updated Jan 28, 2021
• Safety and Efficacy Study in Adult Subjects With Acute Migraines

  NCT03235479

  CompletedInterventionalPhase 3Updated Feb 16, 2023