Migraine
Conditions
Interventions
Investigational drug
Neublastin (also known as BG00010) acts as a selective ligand for the GFRa3
receptor. Neublastin is supplied as a liquid drug product in vials containing
5.0 mL of 1.6 mg/mL Neu
Sponsors
Centre for Human Drug Research
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Male or female from 18 to 65 years of age (inclusive) at screening visit. 3. Body mass index (BMI) between 18 and 35 kg/m2, inclusive at screening, with a minimum weight of 50 kg at screening. 4. Subject is judged by the investigator to be in good health based on medical history (except for migraine in patients participating in Part B) based on all available data prior to administration of initial dose of study drug. 7. Able and willing to provide signed informed consent prior to any study-mandated procedure. Additional inclusion criteria Part B (episodic migraine patients): 9. History of episodic migraine headaches with or without aura for *6 months as determined by a diagnosis provided by a neurologist. 10. Migraine headaches should either fulfil criteria A and B for migraine without aura or criterion C (*Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition,* 2018). A. Headache has at least 2 of the following characteristics: * unilateral location * pulsating quality * moderate or severe pain intensity (*4 on headache questionnaire) * aggravation by or causing avoidance of routine physical activity B. Experiences at least 1 of the following during headache: * nausea and/or vomiting * photophobia and phonophobia C. Headache described as mimicking usual migraine attack treated and responsive to treatment with triptan; 11. Migraine frequency 1 to 7 migraine days per month in each of the 3 months prior to screening. 12. Migraine headaches should be responsive to treatment with non-steroidal anti-inflammatory agents (NSAIDs) and/or triptans.
Exclusion criteria
Exclusion criteria: 1. History of clinically significant cardiovascular, immunological, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, dermatologic, neurological (except for migraine for patients in Part B) or psychiatric disease, as assessed by the investigator that may confound the results of the study or pose an additional risk to the subject by participation in the study. Note: subjects with hay fever or childhood asthma can be enrolled in the study. 2. History of arterial or venous thrombotic or thromboembolic disease. 3. History of stroke or transient ischemic attack. 5. Recent history (within 1 year prior to screening) or presence of a clinically significant chronically painful condition or recent and unresolved acutely painful condition, except for migraine in Part B. 6. History of drug or alcohol abuse (>14 units of alcohol per week) within a year prior to the screening visit. 11. Use of anti-platelet or anti-coagulation therapy, including but not limited to daily aspirin (except for 81 mg daily doses), clopidogrel, prasugrel, ticagrelor, enoxaparin, apixaban, warfarin. 14. Presence of HIV (HIV Ab), hepatitis B (HBsAg, HBAb) or Hepatitis C (HCV Ab) seropositivity at screening. 15. Any malignancy within the past 5 years, except for basal cell or squamous epithelial carcinomas of the skin or carcinoma in situ of the cervix or anus, that have been resected, with no evidence of metastatic disease for 3 years. 25. Use of concomitant medications, including non-prescription medication, nutritional and herbal supplements within 14 days or 5 and * half-lives (whichever is longer) prior to initial dose of study drug, except incidental use of paracetamol. Note: For part B: use of triptans, paracetamol, and NSAIDs are allowed for treatment of migraine headaches. Additional key exclusion criteria Part B (migraine patients): 28. Greater than an average of 7 migraine days per month in each of the last 3 months prior to screening. 29. Other headache disorders (except for episodic tension-type headache
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Endpoints - Parts A and B Assessment of pruritus * The incidence of pruritus in healthy subjects and migraine patients over a 28-day period after challenge with Neublastin or placebo (IV and ID) as measured by items 1 and 2 on the Pruritus Assessment questionnaire * The severity of pruritus in healthy subjects and migraine patients over a 28-day period after challenge with Neublastin or placebo (IV and ID) as measured by item 3 (Pruritus Average NRS) and item 4 (Peak Pruritus NRS) on the Pruritus Assessment questionnaire * The duration of pruritus in healthy subjects and migraine patients over a 28-day period after challenge with Neublastin or placebo (IV and ID) as measured by item 1 on the 5-D Pruritus Scale questionnaire Assessment of rash * The incidence of rash in healthy subjects and migraine patients over a 28-day period after challenge with Neublastin or placebo (IV and ID) as measured by the Rash Assessment questionnaire * The area and severity of rash in healthy subjects and migraine patients over a 28-day period after challenge with Neublastin or placebo (IV and ID) as measured by the Eczema Area and Severity Index (EASI) * The area and severity of rash in healthy subjects and migraine patients over a 28-day period after challenge with Neublastin or placebo (IV and ID) as measured by patient-reported SCORing Atopic Dermatitis (PO-SCORAD) score * Qualitative assessments of rash in healthy subjects and migraine patients over a 28-day period after challenge with Neublastin or placebo (IV and ID) as observed from digital photography of rash * The incidence and severity of erythema in healthy subjects and migraine patients over a 28-day period after challenge with Neublastin or placebo (IV and ID) as measured by the Erythema index Primary Endpoints - Part B Assessment of headache in migraine patients * The incidence of headache in migraine patients over a 28-day period after challenge with Neublastin or placebo (IV) as me | — |
Secondary
| Measure | Time frame |
|---|---|
| Nociceptive thresholds * The pain detection threshold (PDT) for heat-induced pain in healthy subjects and migraine patients over a 28-day period after challenge with Neublastin or placebo (IV and ID) * The PDT for cold-induced pain in healthy subjects and migraine patients over a 28-day period after challenge with Neublastin or placebo (IV and ID) * The PDT for pressure pain in healthy subjects and migraine patients over a 28-day period after challenge with Neublastin or placebo as measured by using a local algometer for the ID group and a pressure cuff for the IV group * The pain tolerance threshold (PTT) for pressure pain in healthy subjects and migraine patients over a 28-day period after challenge with Neublastin or placebo as measured by using a local algometer for the ID group and a pressure cuff for the IV group * The area of secondary hyperalgesia in healthy subjects over a 28-day period after challenge with Neublastin or placebo, for ID administration only, as measured by the Von Frey test Abnormal temperature perception * The incidence of abnormal temperature perception in healthy subjects and migraine patients over a 28-day period after challenge with Neublastin or placebo (IV and ID) as measured by the Abnormal Temperature Perception Assessment * The severity of abnormal temperature perception in healthy subjects and migraine patients over a 28-day period after challenge with Neublastin or placebo as measured by the Abnormal Temperature Perception Assessment * The duration of abnormal temperature perception in healthy subjects and migraine patients over a 28-day period after challenge with Neublastin or placebo as measured by the Abnormal Temperature Perception Assessment Pharmacokinetics * The concentration of Neublastin in serum after a single IV dose of Neublastin in healthy subjects and migraine patients at each time point that sample is collected Safety * The incidence of treatment-emergent serious adverse events thro | — |
Countries
Netherlands
Outcome results
None listed