BIIB092 in Primary Tauopathies: CBS, nfvPPA, sMAPT, and TES

NCT03658135 | Terminated Phase 1 FDA Drug

• 1 other identifier: UCSF-001-AET-1
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

A Phase 1b, Randomized, Double-Blind, Placebo-Controlled, Parallel Cohort Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy Study of Intravenously Infused BIIB092 in Patients with Four Different Primary Tauopathy Syndromes

Conditions

Primary Tauopathies; Corticobasal Degeneration Syndrome; Frontotemporal Lobar Degeneration With Tau Inclusions; MAPT Mutation Carriers, Symptomatic; Traumatic Encephalopathy Syndrome; Nonfluent Aphasia, Progressive

Keywords

CBS, CBD, nfvPPA, FTD, sMAPT, TES

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events

  Assess adverse events during 20 weeks administration BIIB092 or Placebo

  20 weeks

Secondary Outcomes (3)

• Changes in Pharmacokinetic properties of BIIB092 in Plasma

  20 weeks

• Changes in Pharmacokinetic properties of BIIB092 in Cerebrospinal Fluid

  20 weeks

• Changes in Pharmacodynamic effects of BIIB092 on Cerebrospinal Fluid

  20 weeks

Other Outcomes (12)

• Change in whole brain volume on brain MRI

  20 weeks

• Change in regional brain volume on brain MRI

  20 weeks

• Change in functional connectivity on brain MRI

  20 weeks

Study Arms (2)

BIIB092

EXPERIMENTAL

The investigational drug, BIIB092, will be given intravenously, every 4 weeks for 20 weeks

Drug: BIIB092

Placebo

PLACEBO COMPARATOR

Inactive ingredient

Other: Placebo

Interventions

BIIB092 DRUG

BIIB092 is an investigational monoclonal antibody directed at tau protein

BIIB092

Placebo OTHER

Inactive ingredient

Placebo

Eligibility Criteria

• Age: 35 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Between 35 and 80 years of age (inclusive);
• Able to walk at least 10 steps with minimal assistance (stabilization of one arm or use of cane/walker);
• MRI at Screening is consistent with the underlying neurodegenerative disease of the respective diagnostic cohort (i.e., CBS, nfvPPA, sMAPT, or TES), with no large strokes or severe white matter disease;
• Mini Mental State Exam (MMSE) at Screening is between 20 and 30 (inclusive);
• Amyloid beta (Aβ) positron emission tomography (PET) scan (florbetapir or equivalent) at Screening is not consistent with underlying Alzheimer's disease (AD).
• Previous Aβ PET scan negativity (assessed by a certified neuro radiologist) or previous AD CSF biomarker (Aβ)/tau level) negativity may be used instead of performing an Aβ PET scan at Screening at the PI's discretion;
• The following medications are allowed, but must be stable for 2 months prior to
• Screening:
• FDA-approved AD medications
• FDA-approved Parkinson's disease medications;

You may not qualify if:

• Has a reliable study partner who agrees to accompany the participant to visits, and spends at least 5 hours per week with the participant;
• Agrees to 3 lumbar punctures;
• Signed and dated written informed consent obtained from the participant and the participant's study partner in accordance with local IRB regulations;
• Women of childbearing potential (WCBP) must agree to abstain from sex or use an adequate method of contraception for the duration of the Screening period, the study drug treatment period, and for 155 days after the last dose of study drug;
• Males must agree to abstain from sex with WCBP or use an adequate method of contraception for the duration of the study drug treatment period and for 215 days after the last dose of study drug.
• For CBS Only
• Meets 2013 consensus criteria for possible or probable corticobasal degeneration (CBD), CBS subtype (Armstrong et al. 2013).
• For nfvPPA Only
• Meets 2011 consensus criteria for nfvPPA (Gorno-Tempini et al. 2011). Patients meeting 2013 Armstrong criteria for CBS-nfvPPA or 2017 Movement Disorder Society (MDS) criteria for progressive supranuclear palsy and speech/language disorders (PSP-SL) (Höglinger et al. 2017) would be assigned to this cohort since both of these definitions were derived from the 2011 Gorno-Tempini criteria.
• For sMAPT Only
• Has known frontotemporal lobar degeneration- (FTLD-) causative MAPT mutation confirmed in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory (Ghetti et al. 2015);
• CDR-FTLD (Knopman et al. 2008) sum of boxes score ≥ 1.0. Sum of boxes is used instead of the global Clinical Dementia Rating Scale (CDR) because the global CDR does not take into account FTLD specific measures;
• Has any clinical phenotype of sMAPT.
• For TES Only
• Meets 2016 criteria for probable TES (Reams et al. 2016);

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

UCSF Memory and Aging Center

San Francisco, California, 94158, United States

Location

MeSH Terms

Conditions

Pick Disease of the Brain; Primary Progressive Nonfluent Aphasia; Color Vision Defects

Interventions

gosuranemab

Condition Hierarchy (Ancestors)

Frontotemporal Dementia; Frontotemporal Lobar Degeneration; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders; Aphasia, Primary Progressive; TDP-43 Proteinopathies; Neurodegenerative Diseases; Aphasia; Speech Disorders; Language Disorders; Communication Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Vision Disorders; Sensation Disorders; Cone Dystrophy; Eye Diseases, Hereditary; Eye Diseases

Study Officials

• Adam Boxer, MD, PhD

  UCSF Memory and Aging Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind - only investigational pharmacist is unblinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Adam Boxer, MD, PhD, Professor of Neurology

Model Details: This is a phase 1b, randomized, double-blind, placebo-controlled, parallel cohort study of the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy of BIIB092 in patients with 4 different primary tauopathy syndromes: CBS, nfvPPA, sMAPT, and TES. A basket trial design will be used for a parallel evaluation of BIIB092 in four heterogeneous clinicopathological syndromes that share a common molecular target (tau). There will be four cohorts of approximately 8 participants each, one for each specific primary tauopathy syndrome listed above (for a total of approximately 32 participants). For each diagnostic cohort, eligible participants will be randomized 3:1 to active or placebo (i.e., 6 participants receiving BIIB092 and 2 participants receiving placebo). All eligible participants will be administered study drug (BIIB092 or placebo) as an 1-hour intravenous (IV) infusion q4w for 20 weeks (for a total of 6 infusions).

Study Record Dates

• First Submitted: August 13, 2018
• First Posted: September 5, 2018
• Study Start: September 12, 2018
• Primary Completion: December 13, 2019
• Study Completion: December 13, 2019
• Last Updated: December 19, 2019

Record last verified: 2019-12

Locations

US (1)