Primary TauopathiesPhase 1TauBasketNCT03658135
BIIB092 in Primary Tauopathies: CBS, nfvPPA, sMAPT, and TES
A Phase 1 study testing BIIB092 in people with Primary Tauopathies and Corticobasal Degeneration Syndrome, run by University of California, San Francisco at 1 site in United States.
Trial 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 Read more about this study
- Who is it for?
- Ages 35 to 80 years
- Conditions the study is for
- Primary Tauopathies, Corticobasal Degeneration Syndrome, Frontotemporal Lobar Degeneration With Tau Inclusions
- What is being tested?
- BIIB092
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Sep 2018to 13 Dec 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The inclusion criteria are listed below and are the same for each diagnostic cohort, except where noted. Participants must meet all of the specified inclusion criteria to be randomized to study drug (active or placebo) treatment.
- 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).
Show all 28Show fewer
- 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;
- Other medications (except those listed under exclusion criteria) are allowed as long as the dose is stable for 30 days prior to Screening;
- 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);
- At least 5 years or greater between symptom onset and 1st known traumatic brain injury/concussive episode.
Who cannot join
- The exclusion criteria are listed below and are the same for each diagnostic cohort. Participants meeting any of the following exclusion criteria will be excluded from randomization to study drug (active or placebo) treatment.
- A diagnosis of probable AD (McKhann et al. 2011) or progressive supranuclear palsy- Richardson's syndrome (PSP-RS) (Höglinger et al. 2017). Since variants of progressive supranuclear palsy (PSP) are known to cause nfvPPA and CBS, a diagnosis of PSP-SL or progressive supranuclear palsy-corticobasal syndrome (PSP- CBS) would not be exclusionary;
- Any other medical condition other than CBS, nfvPPA, sMAPT or TES that could account for cognitive or motor deficits (e.g., active seizure disorder, stroke, vascular dementia, substance abuse or alcoholism);
- History of a prominent and sustained response to levodopa therapy in the opinion of the PI;
- History of significant cardiovascular, hematologic, renal, or hepatic disease (or laboratory evidence thereof);
- History of major psychiatric illness or untreated depression that in the opinion of the PI would pose a safety risk or interfere with the appropriate interpretation of study data;
Show all 22Show fewer
- Neutrophil count <1,500/mm3, platelets <100,000/mm3, serum creatinine >1.5 x upper limit of normal (ULN), total bilirubin >1.5 x ULN, alanine aminotransferase (ALT) >3 x ULN, aspartate aminotransferase (AST) >3 x ULN, or International Normalized Ratio (INR) >1.2 at Screening evaluations;
- Evidence of any clinically significant findings on Screening or baseline evaluations which, in the opinion of the PI would pose a safety risk or interfere with appropriate interpretation of study data;
- Current or recent history (within four weeks prior to Screening) of a clinically significant bacterial, fungal, or mycobacterial infection;
- Current clinically significant viral infection;
- Major surgery within four weeks prior to Screening;
- Any contraindication for MRI or unable to tolerate MRI scan at Screening;
- Any contraindication to or unable to tolerate lumbar puncture at Screening, including use of anti-coagulant medications such as warfarin. Daily administration of 81 mg aspirin will be allowed as long as the dose is stable for 30 days prior to Screening;
- Participants who, in the opinion of the PI, are unable or unlikely to comply with the dosing schedule or study evaluations;
- Prior treatment with BIIB092;
- Treatment with another investigational drug within 30 days or 5 half-lives of drug before Screening, whichever is longer. Treatment with investigational drugs other than BIIB092 while on study will not be allowed;
- Treatment with systemic corticosteroids within 30 days or 5 half-lives of drug before Screening, whichever is longer. Treatment with systemic corticosteroids while on study will not be allowed;
- Known hypersensitivity to the inactive ingredients in the study drug (BIIB092 or placebo);
- Known to be pregnant or lactating; or positive pregnancy test at Screening or Baseline (Day 1);
- Cancer within 5 years of Screening, except for basal cell carcinoma;
- History of serum or plasma progranulin level less than one standard deviation below the normal participant mean for the laboratory performing the assay;
- History or evidence at Screening of known disease-associated mutations in GRN, TBK1, C9ORF72, TARBP, CHMPB2, or VCP genes (FTLD causative gene mutations not associated with underlying tau pathology).
Trial locations and contacts
1 site in 1 country.
United States1 site
UCSF Memory and Aging Center
San Francisco, California, 94158
About this study
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
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
Read the detailed description
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).
- Conditions
- Primary Tauopathies, Corticobasal Degeneration Syndrome, Frontotemporal Lobar Degeneration With Tau Inclusions, MAPT Mutation Carriers, Symptomatic, Traumatic Encephalopathy Syndrome, Nonfluent Aphasia, Progressive
- Being tested
- BIIB092, Placebo
- Keywords
- CBS, CBD, nfvPPA, FTD, sMAPT, TES
- Medical subject headings
- Pick Disease of the Brain, Primary Progressive Nonfluent Aphasia, Color Vision Defects
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BIIB092Drug
BIIB092 is an investigational monoclonal antibody directed at tau protein
PlaceboOther
Inactive ingredient
| Study group | Role | What they receive |
|---|---|---|
| BIIB092 | Experimental | The investigational drug, BIIB092, will be given intravenously, every 4 weeks for 20 weeks Receives: Drug: BIIB092 |
| Placebo | Placebo comparator | Inactive ingredient Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-Emergent Adverse Events
Assess adverse events during 20 weeks administration BIIB092 or Placebo
Measured: 20 weeks
Secondary outcomes (3)
Changes in Pharmacokinetic properties of BIIB092 in Plasma
Measure steady-state plasma concentrations of BIIB092 and its metabolites
Measured: 20 weeks
Changes in Pharmacokinetic properties of BIIB092 in Cerebrospinal Fluid
Measure steady-state Cerebrospinal fluid concentrations of BIIB092 and its metabolites
Measured: 20 weeks
Changes in Pharmacodynamic effects of BIIB092 on Cerebrospinal Fluid
Measure CSF concentrations of free extracellular tau (eTau)
Measured: 20 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2018
- Study start12 Sep 2018
- Primary completion13 Dec 2019
- Study completion13 Dec 2019
Why it stopped: BIIB092 program discontinued
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary TauopathiesStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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 blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Adam Boxer, University of California, San Francisco
- Investigators
- Adam Boxer, MD, PhD, Principal investigator, UCSF Memory and Aging Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03658135
- Sponsor's protocol ID
- UCSF-001-AET-1
- Acronym
- TauBasket
- Status last verified
- Dec 2019
- First submitted
- 13 Aug 2018
- Last updated
- 19 Dec 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03658135
- Acronym / sponsor ID
- TauBasket / UCSF-001-AET-1
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: BIIB092 program discontinued
- Enrolment
- 22 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Study start
- 12 Sep 2018 (actual)
- Primary completion
- 13 Dec 2019 (actual)
- Study completion
- 13 Dec 2019 (actual)
- First posted
- 5 Sep 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- 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).
| Arm | Type | Receives |
|---|---|---|
| BIIB092 | Experimental | Drug: BIIB092The investigational drug, BIIB092, will be given intravenously, every 4 weeks for 20 weeks |
| Placebo | Placebo comparator | Other: PlaceboInactive ingredient |
Who may qualify
- Ages
- 35 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- The inclusion criteria are listed below and are the same for each diagnostic cohort, except where noted. Participants must meet all of the specified inclusion criteria to be randomized to study drug (active or placebo) treatment.
- 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;
- For CBS Only
- For nfvPPA Only
- For sMAPT Only
Key exclusion criteria (22 listed)
- The exclusion criteria are listed below and are the same for each diagnostic cohort. Participants meeting any of the following exclusion criteria will be excluded from randomization to study drug (active or placebo) treatment.
- A diagnosis of probable AD (McKhann et al. 2011) or progressive supranuclear palsy- Richardson's syndrome (PSP-RS) (Höglinger et al. 2017). Since variants of progressive supranuclear palsy (PSP) are known to cause nfvPPA and CBS, a diagnosis of PSP-SL or progressive supranuclear palsy-corticobasal syndrome (PSP- CBS) would not be exclusionary;
- Any other medical condition other than CBS, nfvPPA, sMAPT or TES that could account for cognitive or motor deficits (e.g., active seizure disorder, stroke, vascular dementia, substance abuse or alcoholism);
- History of a prominent and sustained response to levodopa therapy in the opinion of the PI;
- History of significant cardiovascular, hematologic, renal, or hepatic disease (or laboratory evidence thereof);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BIIB092BIIB092 is an investigational monoclonal antibody directed at tau protein | Drug | BIIB092 |
| PlaceboInactive ingredient | Other | Placebo |
Primary outcome
Incidence of Treatment-Emergent Adverse Events
Time frame: 20 weeks
Assess adverse events during 20 weeks administration BIIB092 or Placebo
3 secondary outcomes
Changes in Pharmacokinetic properties of BIIB092 in Plasma
Time frame: 20 weeks
Changes in Pharmacokinetic properties of BIIB092 in Cerebrospinal Fluid
Time frame: 20 weeks
Changes in Pharmacodynamic effects of BIIB092 on Cerebrospinal Fluid
Time frame: 20 weeks
Results and safety
The study was stopped early (reason given: BIIB092 program discontinued). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2019.
Related trials for Primary Tauopathies
Enrolling by invitationObservational study
Early Molecular Biomarkers for Differentiating Parkinsonian Syndromes
PARKINSON DISEASE (Disorder), Atypical Parkinsonism
RecruitingPhase 1/2
Tributyrin for Progressive Supranuclear Palsy (PSP): Virtual Trial
Parkinson Disease, Multiple System Atrophy
Active, not recruiting
Primary Care Detection of Cognitive Impairment Leveraging Health & Consumer Technologies in Underserved Communities: The MyCog Trial
Dementia, Cognitive Impairment
Recruiting
Evaluation of a Decision-Support Tool for Blood Biomarker Testing for Alzheimer's Disease in Primary Care
Cognitive Abnormality
Not yet recruitingPhase 2
A Study to Evaluate the Safety, Tolerability and Pharmacodynamics of NIO752 in Primary Tauopathies
Progressive Supranuclear Palsy, Corticobasal Degeneration
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Adam Boxer, MD, PhD principal investigator
UCSF Memory and Aging Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BIIB092 in people with Primary Tauopathies and Corticobasal Degeneration Syndrome, run by University of California, San Francisco at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 28 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: BIIB092 program discontinued). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment-Emergent Adverse Events (time frame: 20 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2019.