Clinical trial NCT06848075: A Phase IIb, Randomized, Double-Blind, Placebo-Controlled Study of Elismetrep (K-304) in the Treatment of Migraine
Official title: A Phase IIb, Randomized, Double-Blind, Placebo-Controlled Study of Elismetrep (K-304) in the Treatment of Migraine: A Range of Doses Will be Evaluated
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Acute Migraine
Lead sponsor: Kallyope Inc.
Sponsor class: INDUSTRY
First posted: 2025-02-26
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: Inclusion Criteria:

1. Be a male or female, age 18 to 70 years, inclusive, at the time of signing informed consent.
2. Patient has greater than a one-year history of migraine with or without aura as defined by International Conference on Harmonization (IHS) 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 and confirmed by the investigator.
3. Patient has had ≥2 and ≤10 moderate or severe migraine attacks per month in each of the two months prior to screening (Visit 1).
4. Meet the following requirements:

   1. Is a male OR
   2. Is a female who is of non-childbearing potential defined by at least 1 of the following criteria:
   3. Postmenopausal (aged \>45 years and with a minimum of 12 months of spontaneous amenorrhea with a Screening serum follicle-stimulating hormone (FSH) level in the menopausal range established for the central laboratory.
   4. Post hysterectomy, bilateral oophorectomy or bilateral salpingectomy, based on the subject's recall of their medical history.

      OR
   5. Is a female of reproductive potential and:
   6. agrees to remain abstinent from heterosexual activity\*

      \*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.
   7. or 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 trial (EoT) visit. Acceptable methods of birth control are:

      * combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:

        * oral
        * intravaginal
        * transdermal
      * progestogen-only hormonal contraception associated with inhibition of ovulation:

        * oral
        * injectable
        * implantable
      * intrauterine device (IUD)
      * intrauterine hormone-releasing system (IUS)
      * bilateral tubal occlusion
      * vasectomised partner
      * sexual abstinence
      * progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mode of action
      * male or female condom with or without spermicide
      * cap, diaphragm or sponge with spermicide
      * A combination of male condom with either cap, diaphragm or sponge with spermicide (double barrier methods)

   This condition is waived if the subject is proven to have no child-bearing potential (eg, hysterectomy).
5. Patient voluntarily agrees to participate in the study by giving written informed consent.
6. Patient is able to read, understand and complete the study questionnaires and diary.
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:

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

   Migraine history-related
2. Patient has difficulty distinguishing his/her migraine attacks from tension-type headaches.
3. Patient has a history of predominantly mild migraine attacks or migraines that usually resolve spontaneously in less than two hours.
4. Patient 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 three months prior to screening (Visit 1).
5. Patient has brainstem (a.k.a. basilar-type) or hemiplegic migraine headache, or retinal migraine.
6. Patient was \>50 years old at age of first migraine onset.
7. Patient is taking migraine prophylactic medication where the prescribed daily 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. Patient 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. Patient 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, renal, respiratory, neurologic, gastrointestinal, biliary, or genitourinary abnormalities or diseases 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. Patient 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 (MI), Acute Coronary Syndrome (ACS), percutaneous Coronary Intervention (PCI), cardiac surgery, stroke or transient ischemic attack (TIA) during the 6 months prior to screening.
13. Has a history of human immunodeficiency virus disease.
14. Patient 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 (ECG) related
15. Has a positive test result at Screening for hepatitis B surface antigen (Ag), hepatitis C virus antibody.
16. Has a screening estimated Glomerular Filtration Rate (eGFR) estimated with the Modification of Diet in Renal Disease (MDRD) equation of \<45 ml/min/1.73 m2.
17. Has a screening result for alanine aminotransferase or aspartate aminotransferase (ALT or AST) of \>2.0X upper limit of normal (ULN) or total bilirubin \>1.5X ULN at the Screening visit. Note: An isolated bilirubin \>1.5X ULN is acceptable if bilirubin is fractionated, and direct bilirubin is within the laboratory normal range.
18. Has a corrected QT interval to Fridericia's formula (QTcF) \>450 milliseconds (msec) for males and \>470 msec for females at screening.
19. Has a mean value for triplicate seated systolic blood pressure \>160 mmHg and/or diastolic blood pressure (BP) \>95 mmHg measured after at least 5 minutes at rest at the Screening Visit.

    Note: If a subject's BP is exclusionary on the first triplicate assessment at the Screening visit, they may have 1 repeat triplicate BP 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: 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.
23. Is currently in violation of study requirements for prohibited and permissible concomitant medications (not already specified in other criteria) or is anticipated to violate these requirements during study participation.
24. Has any use of prescription opiate medications within 14 days of screening or any anticipated/potential use of opiates during study participation.
25. History of use of ergotamine medications on greater than/equal 10 days per month on a regular basis for greater than/equal 3 months prior to screening.
26. History of non-narcotic analgesic intake on greater than/equal 15 days per month for greater than/equal 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. Had major surgery or donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the Screening Visit; 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.
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.

Primary outcomes:
measure: Pain freedom
timeFrame: 2 hours post-dose
Secondary outcomes:
measure: Freedom from the most bothersome symptom (MBS) (nausea, phonophobia or photophobia)
timeFrame: 2 hours post-dose
measure: Pain relief
timeFrame: 2 hours post-dose
measure: Freedom from Photophobia
timeFrame: 2 hours post-dose
measure: Freedom from Phonophobia
timeFrame: 2 hours post-dose
measure: Freedom from Nausea
timeFrame: 2 hours post-dose
measure: The probability of requiring rescue medication
timeFrame: 24 hours post-dose
measure: Sustained pain freedom
timeFrame: From 2 to 24 hours
measure: Sustained pain relief
timeFrame: From 2 to 24 hours
measure: Sustained pain freedom
timeFrame: From 2 to 48 hours
measure: Sustained pain relief
timeFrame: From 2 to 48 hours
measure: Proportion of participants who experienced 1 or more treatment-emergent AEs
timeFrame: up to 7 days after administration of study medication
measure: Proportion of participants who experienced 1 or more treatment-emergent SAEs
timeFrame: up to 7 days after administration of study medication
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Central Research Associates, LLC (CRA) dba Flourish Research
state: Alabama
city: Mobile
country: United States
facility: AMR Mobile
state: Alabama
city: Tucson
country: United States
facility: Wake Research/ Tucson Neuroscience Research
state: Arizona
city: Canoga Park
country: United States
facility: Hope Clinical Research
state: California
city: Encino
country: United States
facility: WR-PRI, LLC (Encino)
state: California
city: Huntington Beach
country: United States
facility: Marvel Clinical Research
state: California
city: La Mesa
country: United States
facility: Eximia Research - CA
state: California
city: Lemon Grove
country: United States
facility: Synergy San Diego
state: California
city: Newport Beach
country: United States
facility: WR-PRI, LLC (Newport Beach)
state: California
city: Oceanside
country: United States
facility: Excell Research, Inc.
state: California
city: Pomona
country: United States
facility: Empire Clinical Research
state: California
city: Riverside
country: United States
facility: Artemis Institute for Clinical Research - Riverside
state: California
city: San Diego
country: United States
facility: Acclaim Clinical Research
state: California
city: San Diego
country: United States
facility: Artemis Institute for Clinical Research - San Diego
state: California
city: Walnut Creek
country: United States
facility: Diablo Clinical Research, Inc.
state: California
city: West Hills
country: United States
facility: Focus Clinical Research
state: California
city: Cromwell
country: United States
facility: CT Clinical Research
state: Connecticut
city: Atlanta
country: United States
facility: DelRicht Research
state: Georgia
city: Stockbridge
country: United States
facility: Clinical Research Atlanta - Stockbridge
state: Georgia
city: Boise
country: United States
facility: Northwest Clinical Trials
state: Idaho
city: Chicago
country: United States
facility: Cedar Crosse Research Center
state: Illinois
city: Flossmoor
country: United States
facility: Healthcare Research Network II, LLC
state: Illinois
city: Overland Park
country: United States
facility: Collective Medical Research
state: Kansas
city: Wichita
country: United States
facility: Alliance for Multispecialty Research
state: Kansas
city: Louisville
country: United States
facility: L-MARC Research Center
state: Kentucky
city: Chalmette
country: United States
facility: Crescent City Headache & Neurology Center
state: Louisiana
city: New Orleans
country: United States
facility: DelRicht Research
state: Louisiana
city: Ann Arbor
country: United States
facility: Michigan Head Pain and Neurological Institute
state: Michigan
city: Minneapolis
country: United States
facility: Clinical Research Institute
state: Minnesota
city: Gulfport
country: United States
facility: DelRicht Research
state: Mississippi
city: Hazelwood
country: United States
facility: Healthcare Research Network
state: Missouri
city: Las Vegas
country: United States
facility: Excel Clinical Research
state: Nevada
city: North Las Vegas
country: United States
facility: Las Vegas Clinical Trials
state: Nevada
city: Albuquerque
country: United States
facility: Albuquerque Clinical Trials, Inc.
state: New Mexico
city: Amherst
country: United States
facility: Dent Neurosciences Research Center
state: New York
city: Manlius
country: United States
facility: CNY Clinical Research
state: New York
city: Rochester
country: United States
facility: Rochester Clinical Research
state: New York
city: Williamsville
country: United States
facility: Upstate Clinical Research Associates LLC
state: New York
city: Greensboro
country: United States
facility: Headache Wellness Center
state: North Carolina
city: High Point
country: United States
facility: Peters Medical Research
state: North Carolina
city: Cincinnati
country: United States
facility: CTI Clinical Research Center
state: Ohio
city: Edmond
country: United States
facility: OK Clinical Research, LLC
state: Oklahoma
city: Oklahoma City
country: United States
facility: Hightower Clinical
state: Oklahoma
city: Tulsa
country: United States
facility: DelRicht Research
state: Oklahoma
city: Yukon
country: United States
facility: Tekton Research
state: Oklahoma
city: Portland
country: United States
facility: Summit Research Network
state: Oregon
city: Allentown
country: United States
facility: Lehigh Center for Clinical Research
state: Pennsylvania
city: Philadelphia
country: United States
facility: Clinical Research Philadelphia, LLC
state: Pennsylvania
city: Scottdale
country: United States
facility: Frontier Clinical Research, LLC
state: Pennsylvania
city: Smithfield
country: United States
facility: Frontier Clinical Research, LLC
state: Pennsylvania
city: West Chester
country: United States
facility: Atlas-Clinical
state: Pennsylvania
city: Charleston
country: United States
facility: Clinical Trials of South Carolina
state: South Carolina
city: North Charleston
country: United States
facility: Coastal Carolina Research Center
state: South Carolina
city: Chattanooga
country: United States
facility: WR-ClinSearch
state: Tennessee
city: Knoxville
country: United States
facility: AMR Knoxville (Formerly NOCCR)
state: Tennessee
city: Nashville
country: United States
facility: Clinical Research Associates, Inc.
state: Tennessee
city: Austin
country: United States
facility: Donald J Garcia Jr, MD, PA
state: Texas
city: Austin
country: United States
facility: Tekton Research
state: Texas
city: Dallas
country: United States
facility: FutureSearch Trials of Dallas, LP
state: Texas
city: Houston
country: United States
facility: Victorium Clinical Research LTD CO
state: Texas
city: Splendora
country: United States
facility: APD Clinical Research
state: Texas
city: Waxahachie
country: United States
facility: ClinPoint Trials
state: Texas
city: Ogden
country: United States
facility: Advanced Research Institute
state: Utah
city: Newport News
country: United States
facility: Health Research of Hampton Roads, Inc.
state: Virginia
city: Morgantown
country: United States
facility: Frontier Clinical Research, LLC
state: West Virginia
city: Kenosha
country: United States
facility: Clinical Investigation Specialist
state: Wisconsin
Study officials:
References: