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Multiple Ascending Dose Study of Intravenously Administered BMS-986168 (BIIB092) in Patients With Progressive Supranuclear Palsy (CN002-003)

Primary Purpose

Progressive Supranuclear Palsy

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
BIIB092
Placebo
Sponsored by
Biogen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Progressive Supranuclear Palsy

Eligibility Criteria

41 Years - 86 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria

  1. Probable or possible PSP defined as:

    • at least a 12-month history of postural instability or falls during the first 3 years that symptoms are present
    • a decreased downward saccade velocity at screening defined as observable eye movement deviation from the "main sequence" linear relationship between saccade amplitude and saccade velocity; or supranuclear ophthalmoplegia defined as 50% reduction in upward gaze or 30% reduction in downward gaze; and
    • age at symptom onset of 40 to 85 years by history and current age between 41 and 86 years, inclusive, at the time of screening; and
    • an akinetic-rigid syndrome with prominent axial rigidity.
    • presence of symptoms for less than 5 years.
  2. Body weight range of ≥ 43 kg/95 lbs to ≤ 118 kg/260 lbs.
  3. Able to tolerate MRI.
  4. Able to perform all protocol-specified assessments and comply with the study visit schedule.
  5. Have reliable caregiver to accompany patient to all study visits. Caregiver must be able to read, understand, and speak local language fluently to ensure comprehension of informed consent and informant-based assessments of patient. Caregiver must also have frequent contact with patient (at least 3 hours per week at one time or at different times) and be willing to monitor the patient's health and concomitant medications throughout the study.
  6. Score ≥ 20 on the Mini Mental State Exam (MMSE) at screening.
  7. Patient must reside outside a skilled nursing facility or dementia care facility at the time of screening, and admission to such a facility is not planned. Residence in an assisted living facility is allowed.
  8. Ability to ambulate independently or with assistance defined as the ability to take at least 5 steps with a walker (guarding is allowed provided there is no contact) or the ability to take at least 5 steps without a walker or cane with the assistance of another person who can only have contact with one upper extremity.
  9. Stable on other chronic medications for at least 30 days prior to screening.
  10. Women of child bearing potential (WOCBP) and sexually active fertile men with partners who are WOCBP must use highly effective birth control.

Exclusion Criteria

  1. Presence of other significant neurological or psychiatric disorders.
  2. History of or screening brain MRI scan indicative of significant abnormality.
  3. History of cancer within 5 years of screening with the exception of fully excised non-melanoma skin cancers or non-metastatic prostate cancer that has been stable for at least 6 months.
  4. History of clinically significant hematological, endocrine, cardiovascular, renal, hepatic, gastrointestinal, or neurological disease.
  5. Inability to be venipunctured and/or tolerate venous access.
  6. Contraindication to undergoing an LP.
  7. Recent drug or alcohol abuse as defined in DSM IV.
  8. Treatment with any investigational drugs (including placebo) or devices within 90 days prior to screening.
  9. Contraindication to the MRI examination for any reason
  10. History of a clinically significant medical condition that would interfere with the patient's ability to comply with study instructions, would place the patient at increased risk, or might confound the interpretation of the study results.
  11. History of allergy, hypersensitivity, or serious adverse reaction to monoclonal antibodies or related compounds or allergy to any of the components of the study drug

Sites / Locations

  • The University of Alabama at Birmingham
  • David Geffen School of Medicine at UCLA
  • University of California San Diego
  • University of California, San Francisco, Medical Center at Parnassus
  • Parkinsons Disease and Movement Disorders Center of Boca Raton
  • University of Florida College of Medicine
  • University of South Florida
  • The University of Chicago Department of Neurology
  • University of Minnesota Medical School
  • Robert Wood Johnson Medical School
  • Columbia University Medical Center
  • Hospital of the University of Pennsylvania
  • The University of Texas Southwestern Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Panel 1: BIIB092/ Placebo

Panel 2: BIIB092/ Placebo

Panel 3: BIIB092/ Placebo

Panel 4: BIIB092/ Placebo

Arm Description

BIIB092 or matching placebo administered by intravenous (IV) injection, up to a maximum of 3 doses once every four weeks.

BIIB092 or matching placebo administered by intravenous (IV) injection, up to a maximum of 3 doses once every four weeks.

BIIB092 or matching placebo administered by intravenous (IV) injection, up to a maximum of 3 doses once every four weeks.

BIIB092 or matching placebo administered by intravenous (IV) injection, up to a maximum of 3 doses once every four weeks.

Outcomes

Primary Outcome Measures

Safety and Tolerability as Measured by Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

Secondary Outcome Measures

Percent Change from Baseline in Extracellular Tau (eTau) Concentration in Cerebrospinal Fluid
Immunogenicity of BIIB092 Measured by Presence or Absence of Anti-BIIB092 Antibodies in Serum
Maximum Serum Concentration (Cmax) of BIIB092
Area Under the Concentration Time-curve of BIIB092 in One Dosing Interval (AUC(TAU))
Trough Serum Concentration (Ctrough) of BIIB092
Serum Concentration at 4 Weeks After Dosing of BIIB092
Time of Maximum Serum Concentration (Tmax)

Full Information

First Posted
May 20, 2015
Last Updated
August 30, 2018
Sponsor
Biogen
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1. Study Identification

Unique Protocol Identification Number
NCT02460094
Brief Title
Multiple Ascending Dose Study of Intravenously Administered BMS-986168 (BIIB092) in Patients With Progressive Supranuclear Palsy
Acronym
CN002-003
Official Title
A Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study of Intravenously Administered BMS-986168 in Patients With Progressive Supranuclear Palsy
Study Type
Interventional

2. Study Status

Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
October 2, 2015 (Actual)
Primary Completion Date
October 19, 2016 (Actual)
Study Completion Date
October 19, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biogen

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to evaluate the safety and tolerability of multiple ascending intravenous infusions of BMS-986168 and to assess the pharmacokinetics and immunogenicity of BIIB092, and pharmacodynamics of BIIB092 on cerebrospinal fluid (CSF) extracellular tau (eTau) concentrations in participants with Progressive Supranuclear Palsy.
Detailed Description
This study, previously posted by Bristol-Myers Squibb, has transitioned to Biogen under a licensing agreement.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Progressive Supranuclear Palsy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
48 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Panel 1: BIIB092/ Placebo
Arm Type
Experimental
Arm Description
BIIB092 or matching placebo administered by intravenous (IV) injection, up to a maximum of 3 doses once every four weeks.
Arm Title
Panel 2: BIIB092/ Placebo
Arm Type
Experimental
Arm Description
BIIB092 or matching placebo administered by intravenous (IV) injection, up to a maximum of 3 doses once every four weeks.
Arm Title
Panel 3: BIIB092/ Placebo
Arm Type
Experimental
Arm Description
BIIB092 or matching placebo administered by intravenous (IV) injection, up to a maximum of 3 doses once every four weeks.
Arm Title
Panel 4: BIIB092/ Placebo
Arm Type
Experimental
Arm Description
BIIB092 or matching placebo administered by intravenous (IV) injection, up to a maximum of 3 doses once every four weeks.
Intervention Type
Drug
Intervention Name(s)
BIIB092
Other Intervention Name(s)
BMS-986168
Intervention Description
See Arm Descriptions for dosing information.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
See Arm Descriptions for dosing information. (0.9% Sodium Chloride for Injection or 5% Dextrose Injection if Sodium Chloride is not available)
Primary Outcome Measure Information:
Title
Safety and Tolerability as Measured by Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame
Day 1 - Day 169
Secondary Outcome Measure Information:
Title
Percent Change from Baseline in Extracellular Tau (eTau) Concentration in Cerebrospinal Fluid
Time Frame
Day 1 - Day 85
Title
Immunogenicity of BIIB092 Measured by Presence or Absence of Anti-BIIB092 Antibodies in Serum
Time Frame
Day 1 - Day 169
Title
Maximum Serum Concentration (Cmax) of BIIB092
Time Frame
Day 1 - Day 196
Title
Area Under the Concentration Time-curve of BIIB092 in One Dosing Interval (AUC(TAU))
Time Frame
Day 1 - Day 196
Title
Trough Serum Concentration (Ctrough) of BIIB092
Time Frame
Day 1 - Day 196
Title
Serum Concentration at 4 Weeks After Dosing of BIIB092
Time Frame
Day 1 - Day 196
Title
Time of Maximum Serum Concentration (Tmax)
Time Frame
Day 1 - Day 196

10. Eligibility

Sex
All
Minimum Age & Unit of Time
41 Years
Maximum Age & Unit of Time
86 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Probable or possible PSP defined as: at least a 12-month history of postural instability or falls during the first 3 years that symptoms are present a decreased downward saccade velocity at screening defined as observable eye movement deviation from the "main sequence" linear relationship between saccade amplitude and saccade velocity; or supranuclear ophthalmoplegia defined as 50% reduction in upward gaze or 30% reduction in downward gaze; and age at symptom onset of 40 to 85 years by history and current age between 41 and 86 years, inclusive, at the time of screening; and an akinetic-rigid syndrome with prominent axial rigidity. presence of symptoms for less than 5 years. Body weight range of ≥ 43 kg/95 lbs to ≤ 118 kg/260 lbs. Able to tolerate MRI. Able to perform all protocol-specified assessments and comply with the study visit schedule. Have reliable caregiver to accompany patient to all study visits. Caregiver must be able to read, understand, and speak local language fluently to ensure comprehension of informed consent and informant-based assessments of patient. Caregiver must also have frequent contact with patient (at least 3 hours per week at one time or at different times) and be willing to monitor the patient's health and concomitant medications throughout the study. Score ≥ 20 on the Mini Mental State Exam (MMSE) at screening. Patient must reside outside a skilled nursing facility or dementia care facility at the time of screening, and admission to such a facility is not planned. Residence in an assisted living facility is allowed. Ability to ambulate independently or with assistance defined as the ability to take at least 5 steps with a walker (guarding is allowed provided there is no contact) or the ability to take at least 5 steps without a walker or cane with the assistance of another person who can only have contact with one upper extremity. Stable on other chronic medications for at least 30 days prior to screening. Women of child bearing potential (WOCBP) and sexually active fertile men with partners who are WOCBP must use highly effective birth control. Exclusion Criteria Presence of other significant neurological or psychiatric disorders. History of or screening brain MRI scan indicative of significant abnormality. History of cancer within 5 years of screening with the exception of fully excised non-melanoma skin cancers or non-metastatic prostate cancer that has been stable for at least 6 months. History of clinically significant hematological, endocrine, cardiovascular, renal, hepatic, gastrointestinal, or neurological disease. Inability to be venipunctured and/or tolerate venous access. Contraindication to undergoing an LP. Recent drug or alcohol abuse as defined in DSM IV. Treatment with any investigational drugs (including placebo) or devices within 90 days prior to screening. Contraindication to the MRI examination for any reason History of a clinically significant medical condition that would interfere with the patient's ability to comply with study instructions, would place the patient at increased risk, or might confound the interpretation of the study results. History of allergy, hypersensitivity, or serious adverse reaction to monoclonal antibodies or related compounds or allergy to any of the components of the study drug
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Biogen
Official's Role
Study Director
Facility Information:
Facility Name
The University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
Country
United States
Facility Name
David Geffen School of Medicine at UCLA
City
Los Angeles
State/Province
California
Country
United States
Facility Name
University of California San Diego
City
San Diego
State/Province
California
Country
United States
Facility Name
University of California, San Francisco, Medical Center at Parnassus
City
San Francisco
State/Province
California
Country
United States
Facility Name
Parkinsons Disease and Movement Disorders Center of Boca Raton
City
Boca Raton
State/Province
Florida
Country
United States
Facility Name
University of Florida College of Medicine
City
Gainesville
State/Province
Florida
Country
United States
Facility Name
University of South Florida
City
Tampa
State/Province
Florida
Country
United States
Facility Name
The University of Chicago Department of Neurology
City
Chicago
State/Province
Illinois
Country
United States
Facility Name
University of Minnesota Medical School
City
Minneapolis
State/Province
Minnesota
Country
United States
Facility Name
Robert Wood Johnson Medical School
City
New Brunswick
State/Province
New Jersey
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
Country
United States
Facility Name
Hospital of the University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
Country
United States
Facility Name
The University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
31122495
Citation
Boxer AL, Qureshi I, Ahlijanian M, Grundman M, Golbe LI, Litvan I, Honig LS, Tuite P, McFarland NR, O'Suilleabhain P, Xie T, Tirucherai GS, Bechtold C, Bordelon Y, Geldmacher DS, Grossman M, Isaacson S, Zesiewicz T, Olsson T, Muralidharan KK, Graham DL, O'Gorman J, Haeberlein SB, Dam T. Safety of the tau-directed monoclonal antibody BIIB092 in progressive supranuclear palsy: a randomised, placebo-controlled, multiple ascending dose phase 1b trial. Lancet Neurol. 2019 Jun;18(6):549-558. doi: 10.1016/S1474-4422(19)30139-5.
Results Reference
derived

Learn more about this trial

Multiple Ascending Dose Study of Intravenously Administered BMS-986168 (BIIB092) in Patients With Progressive Supranuclear Palsy

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