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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03658135
• Date of registration: 13/08/2018
• Prospective Registration: Yes
• Primary sponsor: University of California, San Francisco
• Public title: BIIB092 in Primary Tauopathies: CBS, nfvPPA, sMAPT, and TES TauBasket
• Scientific 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
• Date of first enrolment: September 12, 2018
• Target sample size: 22
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT03658135
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Adam Boxer, MD, PhD
• Affiliation: UCSF Memory and Aging Center

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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.

1. Between 35 and 80 years of age (inclusive);

2. Able to walk at least 10 steps with minimal assistance (stabilization of one arm
or use of cane/walker);

3. 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;

4. Mini Mental State Exam (MMSE) at Screening is between 20 and 30 (inclusive);

5. Amyloid beta (Aß) positron emission tomography (PET) scan (florbetapir or
equivalent) at Screening is not consistent with underlying Alzheimer's disease
(AD).

Previous Aß PET scan negativity (assessed by a certified neuro radiologist) or
previous AD CSF biomarker (Aß)/tau level) negativity may be used instead of
performing an Aß PET scan at Screening at the PI's discretion;

6. The following medications are allowed, but must be stable for 2 months prior to

Screening:

1. FDA-approved AD medications

2. FDA-approved Parkinson's disease medications;

7. Other medications (except those listed under exclusion criteria) are allowed as
long as the dose is stable for 30 days prior to Screening;

8. Has a reliable study partner who agrees to accompany the participant to visits,
and spends at least 5 hours per week with the participant;

9. Agrees to 3 lumbar punctures;

10. Signed and dated written informed consent obtained from the participant and the
participant's study partner in accordance with local IRB regulations;

11. 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;

12. 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

13. Meets 2013 consensus criteria for possible or probable corticobasal degeneration
(CBD), CBS subtype (Armstrong et al. 2013).

For nfvPPA Only

14. 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

15. Has known frontotemporal lobar degeneration- (FTLD-) causative MAPT mutation
confirmed in a Clinical Laboratory Improvement Amendments (CLIA) certified
laboratory (Ghetti et al. 2015);

16. 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;

17. Has any clinical phenotype of sMAPT.

For TES Only

18. Meets 2016 criteria for probable TES (Reams et al. 2016);

19. At least 5 years or greater between symptom onset and 1st known traumatic brain
injury/concussive episode.

Exclusion Criteria:

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.

1. 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;

2. 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);

3. History of a prominent and sustained response to levodopa therapy in the opinion of
the PI;

4. History of significant cardiovascular, hematologic, renal, or hepatic disease (or
laboratory evidence thereof);

5. 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;

6. 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;

7. 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;

8. Current or recent history (within four weeks prior to Screening) of a clinically
significant bacterial, fungal, or mycobacterial infection;

9. Current clinically significant viral infection;

10. Major surgery within four weeks prior to Screening;

11. Any contraindication for MRI or unable to tolerate MRI scan at Screening;

12. 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;

13. Participants who, in the opinion of the PI, are unable or unlikely to comply with the
dosing schedule or study evaluations;

14. Prior treatment with BIIB092;

15. 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;

16. Trea


Age minimum: 35 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Frontotemporal Lobar Degeneration With Tau Inclusions

Corticobasal Degeneration Syndrome

Traumatic Encephalopathy Syndrome

MAPT Mutation Carriers, Symptomatic

Primary Tauopathies

Nonfluent Aphasia, Progressive

Intervention(s)

Other: Placebo

Drug: BIIB092

Primary Outcome(s)

Incidence of Treatment-Emergent Adverse Events [Time Frame: 20 weeks]

Secondary Outcome(s)

Changes in Pharmacokinetic properties of BIIB092 in Plasma [Time Frame: 20 weeks]

Changes in Pharmacodynamic effects of BIIB092 on Cerebrospinal Fluid [Time Frame: 20 weeks]

Changes in Pharmacokinetic properties of BIIB092 in Cerebrospinal Fluid [Time Frame: 20 weeks]

Secondary ID(s)

UCSF-001-AET-1

Source(s) of Monetary Support

Please refer to primary and secondary sponsors