Phase 1 Subcutaneous Single and Multiple Ascending Dose Study of BG00010 (Neublastin) - Full Text View

Purpose

The primary objective of the study is to evaluate the safety and tolerability of a range of single intravenous (IV) and subcutaneous (SC) doses of BG00010 in healthy volunteers, and a range of multiple SC doses of BG00010 in participants with painful lumbar radiculopathy. Secondary objectives of this study are to determine the single IV and SC dose pharmacokinetics (PK) profile of BG00010 in healthy volunteers including assessment of bioavailability by comparing SC exposure to IV exposure in each participant, to determine the multiple SC dose PK profiles of BG00010 in participants with painful lumbar radiculopathy, to assess the single IV and SC dose immunogenicity of BG00010 in healthy volunteers, to assess the multiple SC dose immunogenicity of BG00010 in participants with painful lumbar radiculopathy, and to assess the potential of BG00010 to reduce pain following multiple SC administrations in participants with painful lumbar radiculopathy.

Condition	Intervention	Phase
Painful Lumbar Radiculopathy Healthy	Biological: BG00010 IV Biological: BG00010 SC Drug: Placebo IV Drug: Placebo SC	Phase 1


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	Study of Safety, Tolerability, and Pharmacokinetics of BG00010 (Neublastin) Intravenous and Subcutaneous Single Ascending Doses in Healthy Volunteers, and Subcutaneous Multiple Ascending Doses in Subjects With Painful Lumbar Radiculopathy

Further study details as provided by Biogen:

Primary Outcome Measures:

The number of participants with Adverse Events (AEs)/Serious Adverse Events (SAEs) [ Time Frame: Up to Day 75 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Maximum observed concentration (Cmax) of BG00010 [ Time Frame: Pre-dose and up to 24 hours post-dose ] [ Designated as safety issue: No ]
Time to maximum serum concentration (Tmax) of BG00010 [ Time Frame: Pre-dose and up to 24 hours post-dose ] [ Designated as safety issue: No ]
Half life (t1/2) of BG00010 [ Time Frame: Pre-dose and up to 24 hours post-dose ] [ Designated as safety issue: No ]
Area under the serum concentration time curve (AUC) from zero to infinity AUC(0-∞) for BG00010 [ Time Frame: Pre-dose and up to 24 hours post-dose ] [ Designated as safety issue: No ]
Subcutaneous (SC) bioavailability [ Time Frame: Pre-dose and up to 24 hours post-dose ] [ Designated as safety issue: No ]
Number of participants with anti-BG00010 antibodies in serum [ Time Frame: Up to Day 75 ] [ Designated as safety issue: No ]
Pain as measured by an 11-point numeric rating scale (NRS) [ Time Frame: Up to Day 75 ] [ Designated as safety issue: No ]
The Numeric Rating Scale (NRS-11) is an 11-point scale for patient self-reporting of pain. The scale ranges from 0 (no pain) to 10 (worst pain imaginable).
Pain as measured by short form McGill pain questionnaire (SF-MPQ) visual analog scale (VAS) [ Time Frame: Up to Day 75 ] [ Designated as safety issue: No ]
A 10 cm visual analog scale ranging from 0 (no pain) to 10 (worst possible pain).


Enrollment:	54
Study Start Date:	April 2013
Study Completion Date:	August 2014
Primary Completion Date:	August 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Single Ascending Dose (SAD): BG00010 Up to five cohorts of healthy volunteers will receive a single dose of intravenous (IV) BG00010 followed by a single SC dose of BG00010 2 weeks apart.	Biological: BG00010 IV Ascending Doses intravenous (IV) of BG00010 Other Name: Neublastin Biological: BG00010 SC Ascending Doses subcutaneous (SC) of BG00010 Other Name: Neublastin
Experimental: SAD: Placebo Up to five cohorts of healthy volunteers will receive a single IV dose of placebo followed by a single SC dose of placebo 2 weeks apart.	Drug: Placebo IV Ascending Doses intravenous (IV) of Placebo Drug: Placebo SC Ascending Doses subcutaneous (SC) of placebo
Experimental: Multiple Ascending Dose (MAD): BG00010 Up to 6 cohorts of participants with painful lumbar radiculopathy will receive 3 SC doses of BG00010.	Biological: BG00010 SC Ascending Doses subcutaneous (SC) of BG00010 Other Name: Neublastin
Experimental: Multiple Ascending Dose (MAD): Placebo Up to 6 cohorts of participants with painful lumbar radiculopathy will receive 3 SC doses of placebo.	Drug: Placebo SC Ascending Doses subcutaneous (SC) of placebo

Eligibility


Ages Eligible for Study:	18 Years to 75 Years (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Key Inclusion Criteria: Part I and Part II

Healthy Volunteers

Key Inclusion Criteria: Part III multiple ascending dose (MAD)

Subjects must have a diagnosis of unilateral painful lumbar radiculopathy and painful lumbar radiculopathy symptoms must be present for 3 or more months prior to the Screening Visit.
Subjects must rate their pain at ≥40 mm on the 100 mm visual analog scale (VAS) of the short form McGill pain questionnaire (SF-MPQ) at the Screening and Baseline Visits.

Key Inclusion Criteria for All Subjects for Part I, Part II, Part III:

All male subjects and all female subjects of childbearing potential must practice effective contraception during the study and be willing and able to continue contraception for 3 months after their last dose of study treatment. -

Key Exclusion Criteria for All Subjects for Part I, Part II, Part III:

History of or positive screening test for hepatitis C infection , hepatitis B infection, or positive for human immunodeficiency virus (HIV) antibody. Subjects who are hepatitis B surface antigen (HBsAg) negative and hepatitis B core antibody (HBcAb) positive are allowed to participate if they are positive for HBsAb immunoglobulin G
History of malignancy or clinically relevant (as determined by the Investigator) allergies; cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic (not related to painful lumbar radiculopathy), dermatologic, rheumatic/joint, psychiatric, renal, and/or other major disease.
Relevant history of illicit drug or alcohol abuse (as defined by the Investigator) within 1 year prior to the Screening Visit. -
Female subjects who are pregnant or currently breastfeeding, or who have a positive pregnancy test result at the Screening or Baseline Visits.
Previous administration of a neurotrophic factor, including BG00010.
Participation in a study with another investigational drug or approved therapy for investigational use within the 3 months prior to the Baseline Visit, or current enrollment in any other study.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01842126

Locations


Netherlands
Center for Human Drug Research
Leiden, Netherlands

Sponsors and Collaborators

Biogen

Investigators


Study Director:	Medical Director	Biogen

More Information


Responsible Party:	Biogen
ClinicalTrials.gov Identifier:	NCT01842126 History of Changes
Other Study ID Numbers:	103NS103 2012-005224-15
Study First Received:	April 25, 2013
Last Updated:	February 5, 2015
Health Authority:	Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Biogen:


Sciatica

Additional relevant MeSH terms:


Pain Radiculopathy Neurologic Manifestations Nervous System Diseases	Signs and Symptoms Peripheral Nervous System Diseases Neuromuscular Diseases

ClinicalTrials.gov processed this record on September 26, 2016