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

• ClinicalTrials.gov Identifier: NCT02460094
• Recruitment Status: Completed
• First Posted: June 2, 2015
• Last Update Posted: September 4, 2018
• Sponsor: Biogen
• Information provided by (Responsible Party): Biogen

Tracking Information

• First Submitted Date: May 20, 2015
• First Posted Date: June 2, 2015
• Last Update Posted Date: September 4, 2018
• Actual Study Start Date: October 2, 2015
• Actual Primary Completion Date: October 19, 2016 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: August 30, 2018): Safety and Tolerability as Measured by Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Day 1 - Day 169 ]

Original Primary Outcome Measures (submitted: May 29, 2015)

Safety and tolerability, as measured by incidence of AEs, serious AEs, AEs leading to discontinuation, and death as well as marked abnormalities in clinical laboratory tests, vital sign measurements, ECGs, physical and neurological examinations. [ Time Frame: Day 1 - Day 169 ]

To evaluate the safety and tolerability of intravenous (IV) infusions of BMS-986168 in Patients With Progressive Supranuclear Palsy.

Current Secondary Outcome Measures (submitted: August 30, 2018)

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

Original Secondary Outcome Measures (submitted: May 29, 2015)

• Maximum observed serum concentration (Cmax) of BMS-986168. [ Time Frame: Day 1 - Day 169 ]
• Trough serum concentration (Ctrough) of BMS-986168. [ Time Frame: Day 1 - Day 169 ]
• Serum concentration at four weeks after dosing (C4W) of BMS-986168. [ Time Frame: Day 1 - Day 169 ]
• Area under the concentration-time curve in dosing interval (AUC(TAU) of BMS-986168. [ Time Frame: Day 1 - Day 169 ]
• Time of maximum observed serum concentration (Tmax) of BMS-986168. [ Time Frame: Day 1 - Day 169 ]
• Pharmacodynamics (PD) of BMS-986168, measured by CSF for assessment of free eTau and corresponding percent change from baseline. [ Time Frame: Day 1 - Day 169 ]
• Assess immunogenicity of BMS-986168 for the presence or absence of specific drug antibodies (anti-BMS-986168) in serum. [ Time Frame: Day 1 - Day 169 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Progressive Supranuclear Palsy

Intervention

• Drug: BIIB092
  See Arm Descriptions for dosing information.
  Other Name: 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)

Study Arms

• 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.
  Interventions:

  • Drug: BIIB092
  • Drug: Placebo
• 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.
  Interventions:

  • Drug: BIIB092
  • Drug: Placebo
• 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.
  Interventions:

  • Drug: BIIB092
  • Drug: Placebo
• 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.
  Interventions:

  • Drug: BIIB092
  • Drug: Placebo

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 29, 2015): 48
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: October 19, 2016
• Actual Primary Completion Date: October 19, 2016 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 41 Years to 86 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02460094
• Other Study ID Numbers: CN002-003
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Biogen
• Original Responsible Party: Bristol-Myers Squibb
• Current Study Sponsor: Biogen
• Original Study Sponsor: Bristol-Myers Squibb
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Biogen

• PRS Account: Biogen
• Verification Date: August 2018