A Randomized, Blinded, Placebo-Controlled, Single Ascending Dose Study of the Safety, Tolerability, and Pharmacokinetics of BIIB033 in Healthy Adult Volunteers
- Conditions
- demyelinationMS10012303
- Registration Number
- NL-OMON32724
- Lead Sponsor
- Biogen
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 64
1. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations.
2. Aged 25 to 55 years, inclusive, at the time of informed consent.
3. Must be in good health as determined by the Investigator, based on medical history and screening evaluations.
4. Must have a BMI of 18 to 30 kg/m2, inclusive. (Note: subjects enrolled into any dose level less than 1 mg/kg must have a body weight of at least 60 kg.)
5. All male subjects must practice effective contraception during the study and be willing and able to continue contraception for at least 6 months after their dose of study treatment. Females of childbearing potential, unless postmenopausal or surgically sterile, are not allowed to enter the study.
1. History of any clinically significant cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, or other major disease, as determined by the Investigator.
2. Clinically significant abnormal clinical laboratory test values, as determined by the Investigator, or any values for alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, or creatinine that are above the upper limit of normal, any values for platelets or hemoglobin that are below the lower limit of normal, or any clinically significant out of normal range values for white blood cells.
3. Clinically significant (as determined by the Investigator) 12 lead ECG abnormalities, including corrected QT interval using Bazett*s correction method of >450 msec for males and >470 msec for females.
4. (For selected cohorts) Any history of lumbar surgery for any reason (e.g., hernia), or contraindications to having an LP, including prominent chronic back pain or prominent scoliosis, or a refractory or prolonged headache or other complication after the screening LP that does not resolve within 5 days with conservative treatment. Note: All post LP symptoms must have resolved prior to randomization.
5. Any contraindications to having a brain MRI.
6. History of severe allergic or anaphylactic reactions.
7. Subjects who have plans to undergo elective procedures/surgeries at any time during the study through the Follow-Up visits.
8. Known history of or positive test result for human immunodeficiency virus.
9. Known history of or positive test result for HCVAb, HBcAb, or HBsAg.
10. Serious infection (e.g., pneumonia, septicemia) as determined by the Investigator within the 3 months prior to Day -1.
11. Fever or bacterial, or viral infection (including upper respiratory tract infection) within 2 weeks prior to Day -1.
12. Treatment with any prescription medication within the 28 days prior to Day -1.
13. Treatment with any over-the-counter products, including herbal and/or alternative health preparations and procedures within the 14 days prior to Day -1. (Intermittent treatment with paracetamol [*1000 mg/day] and/or ibuprofen [*400 mg/day] is permitted.)
14. Current enrollment in any other drug, biologic, device, or clinical study, or treatment with an investigational drug or approved therapy for investigational use within 30 days (or 5 half lives, whichever is longer) prior to Day -1.
15. Any live or attenuated immunization/vaccination within 1 month prior to the study drug infusion or planned to occur during the study period.
16. Blood donation (1 unit or more) within 1 month prior to Screening.
17. History of alcohol or substance abuse (as determined by the Investigator), a positive urine drug/alcohol test at Screening or Day -1, or alcohol use within 48 hours prior to Day -1.
18. Inability to comply with study requirements.
19. Vigorous exercise (as determined by the Investigator) within 48 hours prior to the study drug infusion.
20. Regular use of any tobacco product within 3 months prior to Day -1.
21. Other unspecified reasons that, in the opinion of the Investigator or Biogen Idec, make the subject unsuitable for enrollment.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary study parameters:<br /><br>* incidence of adverse events (AEs)<br /><br>* incidence of serious adverse events (SAEs)<br /><br>* clinical laboratory assessments and vital signs<br /><br>* other safety measures: physical, neurological and retinal examinations,<br /><br>electrocardiogram (ECG), brain magnetic resonance imaging (MRI), visual evoked<br /><br>potentials (VEP), somatosensory evoked potentials (SSEP) and<br /><br>electroencephalogram (EEG).</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary study parameters:<br /><br>* serum BIIB033 concentrations and PK parameters: area under the concentration<br /><br>curve (AUC), maximum (peak) serum concentration (Cmax,), time to maximum serum<br /><br>concentration (Tmax), elimination half life (t*), clearance (Cl), and volume of<br /><br>distribution (Vd)<br /><br>* incidence of anti-BIIB033 serum antibodies<br /><br>* exploratory biomarker profiles in blood, urine and CSF (selected cohorts)</p><br>