Clinical trial NCT02460094: Multiple Ascending Dose Study of Intravenously Administered BMS-986168 (BIIB092) in Patients With Progressive Supranuclear Palsy
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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Progressive Supranuclear Palsy
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2015-06-02
Enrollment: 48
Sex: ALL
Minimum age (years): 41
Maximum age (years): 86
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety and Tolerability as Measured by Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Day 1 - Day 169
Secondary outcomes:
measure: Percent Change from Baseline in Extracellular Tau (eTau) Concentration in Cerebrospinal Fluid
timeFrame: Day 1 - Day 85
measure: Immunogenicity of BIIB092 Measured by Presence or Absence of Anti-BIIB092 Antibodies in Serum
timeFrame: Day 1 - Day 169
measure: Maximum Serum Concentration (Cmax) of BIIB092
timeFrame: Day 1 - Day 196
measure: Area Under the Concentration Time-curve of BIIB092 in One Dosing Interval (AUC(TAU))
timeFrame: Day 1 - Day 196
measure: Trough Serum Concentration (Ctrough) of BIIB092
timeFrame: Day 1 - Day 196
measure: Serum Concentration at 4 Weeks After Dosing of BIIB092
timeFrame: Day 1 - Day 196
measure: Time of Maximum Serum Concentration (Tmax)
timeFrame: Day 1 - Day 196
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: The University of Alabama at Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at UCLA
state: California
city: San Diego
country: United States
facility: University of California San Diego
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco, Medical Center at Parnassus
state: California
city: Boca Raton
country: United States
facility: Parkinsons Disease and Movement Disorders Center of Boca Raton
state: Florida
city: Gainesville
country: United States
facility: University of Florida College of Medicine
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Chicago
country: United States
facility: The University of Chicago Department of Neurology
state: Illinois
city: Minneapolis
country: United States
facility: University of Minnesota Medical School
state: Minnesota
city: New Brunswick
country: United States
facility: Robert Wood Johnson Medical School
state: New Jersey
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Dallas
country: United States
facility: The University of Texas Southwestern Medical Center
state: Texas
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References:
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.