Phase 2 Study of BIIB092 in Participants With Early Alzheimer's Disease (TANGO)

• ClinicalTrials.gov Identifier: NCT03352557
• Recruitment Status: Active, not recruiting
• First Posted: November 24, 2017
• Last Update Posted: February 7, 2020
• Sponsor: Biogen
• Information provided by (Responsible Party): Biogen

Tracking Information

• First Submitted Date: November 21, 2017
• First Posted Date: November 24, 2017
• Last Update Posted Date: February 7, 2020
• Actual Study Start Date: May 3, 2018
• Estimated Primary Completion Date: March 26, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 3, 2019)

Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to Week 238 ]

AEs: any sign, symptom, or diagnosis/disease that is unfavorable or unintended, that is new, or if pre-existing, worsens in participants administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. SAEs: an event that results in death; an event that, in the view of the investigator, places the participant at immediate risk of death (a life-threatening event); an outcome that results in a congenital anomaly/birth defect diagnosed in a child of a participant; an event that requires or prolongs inpatient hospitalization; an event that results in persistent or significant disability/incapacity. Any other medically important event that, in the opinion of the investigator, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed in the definition above.

Original Primary Outcome Measures (submitted: November 21, 2017)

• Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to Week 90 ]
  AEs: any sign, symptom, or diagnosis/disease that is unfavorable or unintended, that is new, or if pre-existing, worsens in participants administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. SAEs: an event that results in death; an event that, in the view of the investigator, places the participant at immediate risk of death (a life-threatening event); an outcome that results in a congenital anomaly/birth defect diagnosed in a child of a participant; an event that requires or prolongs inpatient hospitalization; an event that results in persistent or significant disability/incapacity. Any other medically important event that, in the opinion of the investigator, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed in the definition above.
• Percentage of Participants With Abnormal Laboratory Safety Assessments [ Time Frame: From Baseline up to Week 90 ]
• Percentage of Participants With Changes From Baseline Over Time in Laboratory Safety Assessments [ Time Frame: From Baseline up to Week 90 ]
• Percentage of Participants With Abnormal Vital Signs [ Time Frame: From Baseline up to Week 90 ]
• Percentage of Participants With Changes From Baseline Over Time in Vital Signs [ Time Frame: From Baseline up to Week 90 ]
• Percentage of Participants With Abnormal 12-Lead Electrocardiogram (ECG) Assessments [ Time Frame: From Bseline up to Week 90 ]
• Percentage of Participants With Changes From Baseline in Over Time in 12-Lead Electrocardiogram (ECG) Assessments [ Time Frame: From Baseline up to Week 90 ]
• Percentage of Participants With Changes in Physical Examinations Assessments [ Time Frame: From Baseline up to Week 90 ]

Current Secondary Outcome Measures (submitted: August 17, 2018)

• Change From Baseline Over Time at Week 78 on the Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) [ Time Frame: From Baseline to Week 78 ]
  The CDR-SB is a validated clinical assessment of global function in participants with AD. Impairment is scored in each of 6 cognitive categories on a scale in which none = 0, questionable = 0.5, mild = 1, moderate = 2, and severe = 3. The 6 individual category ratings, or "box scores", can be added together to give the CDR-SB which ranges from 0 to 18 (severe impairment).
• Percentage of Participants With Anti-BIIB092 Antibodies in Serum Over Time up to Week 90 [ Time Frame: From Baseline up to Week 90 ]

Original Secondary Outcome Measures (submitted: November 21, 2017)

• Change From Baseline Over Time at Week 78 on the Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) [ Time Frame: From Baseline to Week 78 ]
  The CDR-SB is a validated clinical assessment of global function in patients with AD. Impairment is scored in each of 6 cognitive categories on a scale in which none = 0, questionable = 0.5, mild = 1, moderate = 2, and severe = 3. The 6 individual category ratings, or "box scores", can be added together to give the CDR-SB which ranges from 0 to 18 (severe impairment).
• Percentage of Participants With Anti-BIIB092 Antibodies in Serum Over Time up to Week 90 [ Time Frame: From Baseline up to Week 90 ]

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

Descriptive Information

• Brief Title: Phase 2 Study of BIIB092 in Participants With Early Alzheimer's Disease
• Official Title: Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Assess the Safety, Tolerability, and Efficacy of BIIB092 in Subjects With Mild Cognitive Impairment Due to Alzheimer's Disease or With Mild Alzheimer's Disease

Brief Summary

The primary objective of the placebo-controlled period is to evaluate the safety and tolerability of BIIB092 in participants with mild cognitive impairment (MCI) due to Alzheimer's disease (AD) or with mild AD. The secondary objectives of the placebo-controlled period are to evaluate the efficacy of multiple doses of BIIB092 in slowing cognitive and functional impairment in participants with MCI due to AD or with mild AD, and to evaluate the immunogenicity of BIIB092 after multiple doses in participants with MCI due to AD or with mild AD.

The primary objective of the long-term extension period is to evaluate the long-term safety and tolerability of BIIB092 in participants with MCI due to AD or with mild AD.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Alzheimer's Disease

Intervention

• Drug: BIIB092
  Administered as specified in treatment arm.
  Other Name: Formally known as BMS 986168
• Drug: Placebo
  Administered as specified in treatment arm.

Study Arms

• Experimental: Low-dose BIIB092
  Intravenous (IV) infusion once every 4 weeks OR once every 12 weeks and placebo at the other 4-week dosing visits to maintain the treatment blind.
  Intervention: Drug: BIIB092
• Experimental: Medium-dose BIIB092
  Intravenous (IV) infusion once every 4 weeks.
  Intervention: Drug: BIIB092
• Experimental: High-dose BIIB092
  Intravenous (IV) infusion once every 4 weeks.
  Intervention: Drug: BIIB092
• Placebo Comparator: Placebo
  Intravenous (IV) infusion once every 4 weeks.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: September 19, 2019): 654
• Original Estimated Enrollment (submitted: November 21, 2017): 528
• Estimated Study Completion Date: March 26, 2024
• Estimated Primary Completion Date: March 26, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Must have a gradual and progressive change in memory function over more than 6 months.
• Must meet all of the clinical criteria for mild cognitive impairment (MCI) due to Alzheimer's disease (AD) or mild AD and must have
• Objective evidence of cognitive impairment at Screening
• Clinical Dementia Rating Scale (CDR) global score of 0.5 for MCI due to AD or 0.5 or 1 for mild AD
• Mini-Mental State Examination (MMSE) score of 22 to 30 (inclusive)
• CDR Memory Box score of ≥0.5
• Must consent to apolipoprotein E (ApoE) genotyping
• Must have 1 informant/study partner
• Must have amyloid beta positivity confirmed at Screening

Key Exclusion Criteria:

• Any medical or neurological/neurodegenerative condition (other than AD) that, in the opinion of the Investigator, might be a contributing cause to the participant's cognitive impairment or could lead to discontinuation, lack of compliance, interference with study assessments, or safety concerns
• Clinically significant, unstable psychiatric illness
• Have had a stroke or Transient Ischemic Attack (TIA) or unexplained loss of consciousness in the past 1 year
• Relevant brain hemorrhage, bleeding disorder and cerebrovascular abnormalities
• History of unstable angina, myocardial infarction, chronic heart failure or clinically significant conduction abnormalities within 1 year prior to Screening Visit 1
• Indication of impaired renal or liver function
• Alcohol or substance abuse in past 1 year
• Clinically significant systemic illness or serious infection within 30 days prior to or during the screening period
• Use of allowed medications for chronic conditions at doses that have not been stable for at least 4 weeks prior to Screening Visit 1 and during the screening period up to Study Day 1, or use of AD medications at doses that have not been stable for at least 8 weeks prior to Screening Visit 1 and during the screening period up to Study Day 1.
• Use of any medications that, in the opinion of the Investigator, may contribute to cognitive impairment, put the participants at higher risk for adverse events (AEs), or impair the participant's ability to perform cognitive testing or complete study procedures.
• Contraindications to study procedures

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, France, Germany, Italy, Japan, Poland, Spain, Sweden, United States

Administrative Information

• NCT Number: NCT03352557
• Other Study ID Numbers: 251AD201; 2017-002901-37 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Biogen
• Study Sponsor: Biogen
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Biogen

• PRS Account: Biogen
• Verification Date: February 2020