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

A Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study of Intravenously Administered BMS-986168 in Patients With Progressive Supranuclear Palsy

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.

Study Overview

• Status: Completed
• Conditions: Progressive Supranuclear Palsy
• Intervention / Treatment: Drug: BIIB092; Drug: Placebo

Detailed Description

This study, previously posted by Bristol-Myers Squibb, has transitioned to Biogen under a licensing agreement.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States
      • The University of Alabama at Birmingham
  • California
    • Los Angeles, California, United States
      • David Geffen School of Medicine at UCLA
    • San Diego, California, United States
      • University of California San Diego
    • San Francisco, California, United States
      • University of California, San Francisco, Medical Center at Parnassus
  • Florida
    • Boca Raton, Florida, United States
      • Parkinsons Disease And Movement Disorders Center Of Boca Raton
    • Gainesville, Florida, United States
      • University of Florida College of Medicine
    • Tampa, Florida, United States
      • University of South Florida
  • Illinois
    • Chicago, Illinois, United States
      • The University of Chicago Department of Neurology
  • Minnesota
    • Minneapolis, Minnesota, United States
      • University of Minnesota Medical School
  • New Jersey
    • New Brunswick, New Jersey, United States
      • Robert Wood Johnson Medical School
  • New York
    • New York, New York, United States
      • Columbia University Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States
      • Hospital of the University of Pennsylvania
  • Texas
    • Dallas, Texas, United States
      • The University Of Texas Southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 39 years to 84 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Panel 1: BIIB092/ Placebo; BIIB092 or matching placebo administered by intravenous (IV) injection, up to a maximum of 3 doses once every four weeks.	Drug: BIIB092; See Arm Descriptions for dosing information.; Other Names: BMS-986168; Drug: Placebo; See Arm Descriptions for dosing information. (0.9% Sodium Chloride for Injection or 5% Dextrose Injection if Sodium Chloride is not available)
Experimental: Panel 2: BIIB092/ Placebo; BIIB092 or matching placebo administered by intravenous (IV) injection, up to a maximum of 3 doses once every four weeks.	Drug: BIIB092; See Arm Descriptions for dosing information.; Other Names: BMS-986168; Drug: Placebo; See Arm Descriptions for dosing information. (0.9% Sodium Chloride for Injection or 5% Dextrose Injection if Sodium Chloride is not available)
Experimental: Panel 3: BIIB092/ Placebo; BIIB092 or matching placebo administered by intravenous (IV) injection, up to a maximum of 3 doses once every four weeks.	Drug: BIIB092; See Arm Descriptions for dosing information.; Other Names: BMS-986168; Drug: Placebo; See Arm Descriptions for dosing information. (0.9% Sodium Chloride for Injection or 5% Dextrose Injection if Sodium Chloride is not available)
Experimental: Panel 4: BIIB092/ Placebo; BIIB092 or matching placebo administered by intravenous (IV) injection, up to a maximum of 3 doses once every four weeks.	Drug: BIIB092; See Arm Descriptions for dosing information.; Other Names: BMS-986168; Drug: Placebo; See Arm Descriptions for dosing information. (0.9% Sodium Chloride for Injection or 5% Dextrose Injection if Sodium Chloride is not available)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety and Tolerability as Measured by Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)	Day 1 - Day 169

Secondary Outcome Measures

Outcome Measure	Time Frame
Percent Change from Baseline in Extracellular Tau (eTau) Concentration in Cerebrospinal Fluid	Day 1 - Day 85
Immunogenicity of BIIB092 Measured by Presence or Absence of Anti-BIIB092 Antibodies in Serum	Day 1 - Day 169
Maximum Serum Concentration (Cmax) of BIIB092	Day 1 - Day 196
Area Under the Concentration Time-curve of BIIB092 in One Dosing Interval (AUC(TAU))	Day 1 - Day 196
Trough Serum Concentration (Ctrough) of BIIB092	Day 1 - Day 196
Serum Concentration at 4 Weeks After Dosing of BIIB092	Day 1 - Day 196
Time of Maximum Serum Concentration (Tmax)	Day 1 - Day 196

Collaborators and Investigators

• Sponsor: Biogen

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 2, 2015
• Primary Completion (Actual): October 19, 2016
• Study Completion (Actual): October 19, 2016

Study Registration Dates

• First Submitted: May 20, 2015
• First Submitted That Met QC Criteria: May 29, 2015
• First Posted (Estimate): June 2, 2015

Study Record Updates

• Last Update Posted (Actual): September 4, 2018
• Last Update Submitted That Met QC Criteria: August 30, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Eye Diseases; Neurologic Manifestations; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Tauopathies; Cranial Nerve Diseases; Ocular Motility Disorders; Paralysis; Ophthalmoplegia; Supranuclear Palsy, Progressive
• Other Study ID Numbers: CN002-003