BIIB092 in Primary Tauopathies: CBS, nfvPPA, sMAPT, and TES (TauBasket)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03658135|
Recruitment Status : Recruiting
First Posted : September 5, 2018
Last Update Posted : September 5, 2018
|Condition or disease||Intervention/treatment||Phase|
|Primary Tauopathies Corticobasal Degeneration Syndrome Frontotemporal Lobar Degeneration With Tau Inclusions MAPT Mutation Carriers, Symptomatic Traumatic Encephalopathy Syndrome Nonfluent Aphasia, Progressive||Drug: BIIB092 Other: Placebo||Phase 1|
This is a phase 1b randomized, double-blind, safety, and tolerability clinical trial of an investigational drug, called BIIB092 in patients with four different primary tauopathy syndromes: amyloid PET (-) corticobasal syndrome (CBS), nonfluent variant primary progressive aphasia (nfvPPA), symptomatic patients with autosomal dominant genetic forms of frontotemporal lobar degeneration (FTD) due to the presence of a mutation in the microtubule-associated protein tau gene (sMAPT), and traumatic encephalopathy syndromes (TES). Primary tauopathies are neurodegenerative brain disorders in which tau is the only protein that accumulates at autopsy. While Alzheimer's disease (AD) is the most common tauopathy, it is considered a secondary tauopathy, because tau protein accumulates along with another pathogenic protein, amyloid beta. Primary tauopathies are rare diseases for which there is no treatment or cure. The purpose of the this study is to characterize the safety and tolerability profile of intravenous BIIB092 in four primary tauopathies.
A basket design will be used for a parallel evaluation of BIIB092 in four heterogenous clinicopathological syndromes that share a common molecular target (tau).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||32 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||
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).
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Masking Description:||Double-blind - only investigational pharmacist is unblinded|
|Official Title:||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|
|Estimated Study Start Date :||September 12, 2018|
|Estimated Primary Completion Date :||December 31, 2019|
|Estimated Study Completion Date :||April 30, 2020|
The investigational drug, BIIB092, will be given intravenously, every 4 weeks for 20 weeks
BIIB092 is an investigational monoclonal antibody directed at tau protein
Placebo Comparator: Placebo
- Incidence of Treatment-Emergent Adverse Events [ Time Frame: 20 weeks ]Assess adverse events during 20 weeks administration BIIB092 or Placebo
- Changes in Pharmacokinetic properties of BIIB092 in Plasma [ Time Frame: 20 weeks ]Measure steady-state plasma concentrations of BIIB092 and its metabolites
- Changes in Pharmacokinetic properties of BIIB092 in Cerebrospinal Fluid [ Time Frame: 20 weeks ]Measure steady-state Cerebrospinal fluid concentrations of BIIB092 and its metabolites
- Changes in Pharmacodynamic effects of BIIB092 on Cerebrospinal Fluid [ Time Frame: 20 weeks ]Measure CSF concentrations of free extracellular tau (eTau)
- Change in whole brain volume on brain MRI [ Time Frame: 20 weeks ]Measure of global volume of interest (whole brain)
- Change in regional brain volume on brain MRI [ Time Frame: 20 weeks ]Measure of regional volumes of interest (such as ventricles, hippocampus)
- Change in functional connectivity on brain MRI [ Time Frame: 20 weeks ]Connectivity between brain regions measured using arterial spin labeling (ASL)
- Change in functional connectivity on brain MRI [ Time Frame: 20 weeks ]Connectivity between brain regions measured using resting state functional MRI (rsfMRI)
- Change in functional connectivity on brain MRI [ Time Frame: 20 weeks ]Connectivity between brain regions measured using diffusion tensor MRI (DTI)
- Change in Cerebrospinal Fluid Biomarkers of phosphorylated tau [ Time Frame: 20 weeks ]Measure CSF concentrations of phosphorylated tau protein (p-tau) pg/mL
- Change in Cerebrospinal Fluid Biomarkers of neurofilament light chain [ Time Frame: 20 weeks ]Measure CSF concentrations of neurofilament light chain protein (NfL) pg/mL
- Change in Cerebrospinal Fluid Biomarkers of total tau [ Time Frame: 20 weeks ]Measure CSF concentrations of total tau protein (t-tau) pg/mL
- Change in Schwab and England Activities of Daily Living (SEADL) scale [ Time Frame: 20 weeks ]The SEADL assesses the subject's ability to perform daily activities as reported by the subject, caregiver, and clinician. Rated in 10% increments, with 100% = completely independent to 0% = bedridden and vegetative functions.
- Changes in Functional Activities Questionnaire (FAQ) [ Time Frame: 20 weeks ]The FAQ measures the subject's ability to perform common activities independently as reported by informant (such as paying bills, preparing a meal, keeping track of current events). Normal = 0 and dependent on others = 3; Sum scores (range 0-30, with higher score impaired function and possible cognitive impairment)
- Change in Montreal Cognitive Assessment (MoCA) [ Time Frame: 20 weeks ]The MoCA is a brief 30-question test assessing cognitive abilities (such as orientation, short-term memory, executive function/visuospatial ability). Scores range from zero to 30, with a higher score generally considered normal; lower scores indicate possible cognitive impairment.
- Change in Neuropsychiatric Inventory-Questionnaire (NPI-Q) [ Time Frame: 20 weeks ]The NPI-Q is a brief assessment of neuropsychiatric symptoms (such as delusions, hallucinations). Each symptom is rated (by informant/caregiver) for Severity on a 3-point scale (mild, moderate, severe) and Distress on a 5-point scale (0 to 5). The higher the total Severity and Distress scores the more impactful the symptoms.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03658135
|Contact: Mary Koestler, RN, PhDfirstname.lastname@example.org|
|Contact: Lauren Fisher, B.A.||email@example.com|
|United States, California|
|UCSF Memory and Aging Center||Recruiting|
|San Francisco, California, United States, 94158|
|Contact: Mary Koestler, RN, PhD 415-476-0661 firstname.lastname@example.org|
|Contact: Lauren Fisher, BA 415-514-5745 email@example.com|
|Principal Investigator: Adam Boxer, MD, PhD|
|Principal Investigator:||Adam Boxer, MD, PhD||UCSF Memory and Aging Center|