Migraine MedDRA version: 20.0 Level: PT Classification code 10027599 Term: Migraine System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Name: Neublastin
Product Code: BG00010
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: NEUBLASTIN
Other descriptive name: NEUBLASTIN
Concentration unit: µg/kg microgram(s)/kilo
Sponsors
Centre for Human Drug Research
Eligibility
Sex/Gender
All
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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 48 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
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. 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 ½ half-lives (whichever is longer) prior to initial dose of study drug, except incidental use of paracetamol. 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 <5 days/month). 30. Greater than or equal to 5 headache days per month of any type/diagnosis (except migraine) in each of the last 3 months prior to screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Objectives 1. To assess pruritus and rash after administration of Neublastin or placebo in healthy subjects and migraine patients (Parts A and B) 2. To assess headache and other migraine-associated symptoms after administration of Neublastin or placebo in migraine patients (Part B) ;Secondary Objective: Secondary Objectives 1. To assess Neublastin-induced mechanical and thermal sensory responses using nociceptive thresholds in healthy subjects and migraine patients (Parts A and B) 2. To assess headache and other migraine-associated symptoms in healthy subjects upon administration of Neublastin or placebo (Part A) 3. To assess changes in temperature perception upon administration of Neublastin or placebo in healthy subjects and migraine patients (Parts A and B) 4. To characterize the pharmacokinetics (PK) profile of a single IV dose of Neublastin in healthy subjects and in migraine patients (Parts A and B) 5. To characterize the safety and tolerability of a single IV dose of Neublastin in healthy subjects and in migraine patients (Parts A and B) 6. To characterize the safety and tolerability of Neublastin administered intradermally (ID) in healthy subjects (Part A) ;Primary end point(s): Safety and tolerability endpoints Parts A and B, IV administration • The incidence of treatment-emergent serious adverse events throughout the duration of the study in healthy subjects and migraine patients challenged with a single IV dose of Neublastin compared to placebo Part A, ID administration • The incidence of treatment-emergent serious adverse events throughout the duration of the study in healthy subjects challenged with Neublastin or placebo administered ID Pharmacokinetic endpoints Parts A and B, IV administration The PK variable is the concentration of Neublastin in serum at each time point that sample is collected. Pharmacodynamic endpoints All parameters will be compared to baseline; baseline is defined as the last value prior to dosing. Pr | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Day - 1 - EOS;Secondary end point(s): Secondary Endpoints - Parts A and B 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 | — |
Countries
Netherlands
Contacts
Public ContactPrincipal Investigator
Centre for Human Drug Research
Outcome results
None listed