Clinical trial NCT02985879: A Study to Assess Efficacy, Safety, Tolerability, and Pharmacokinetics of ABBV-8E12 in Subjects With Progressive Supranuclear Palsy (PSP)
Official title: A Randomized, Double-Blind, Placebo-Controlled Multiple Dose Study to Assess Efficacy, Safety, Tolerability, and Pharmacokinetics of ABBV-8E12 in Progressive Supranuclear Palsy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Progressive Supranuclear Palsy
Keywords: PSP
Steele-Richardson-Olszewski syndrome
Tauopathy
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2016-12-07
Enrollment: 378
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to assess efficacy, safety, tolerability, and pharmacokinetics of ABBV-8E12 in participants with progressive supranuclear palsy (PSP).

Detailed description: This was a Phase 2, randomized, double-blind, placebo-controlled, multiple dose, multicenter study consisting of a screening period of up to 8 weeks (56 days), a 52-week double-blind treatment period, and a post-treatment follow-up period of approximately 20 weeks following last study drug administration (for those participants who prematurely discontinued from treatment, declined to participate in or did not qualify for participation in a long term extension \[LTE\] study). At the end of the treatment period, extended treatment was available for eligible participants who completed the 52-week treatment period and entered the separate long-term extension study (NCT03391765; Study M15-563). There were 3 cohorts in the study (Cohort 1, Cohort J1, and Cohort 2). Cohort 1 had augmented safety and pharmacokinetic (PK) assessments in the first 30 participants enrolled into the global study from countries other than Japan. Cohort J1 had augmented safety and PK assessments in the first 9 participants enrolled into the study from Japan. Cohort 2 consisted of all other participants enrolled in the global study not participating in Cohort 1 or Cohort J1.

This study was prematurely discontinued because the program for progressive supranuclear palsy was discontinued due to lack of efficacy of study drug.

Eligibility criteria: Key Inclusion Criteria:

* Male or female participant with age 40 years or greater at the time of signed consent
* Meets the criteria for possible or probable progressive supranuclear palsy (PSP; Steele-Richardson-Olszewski Syndrome)
* Presence of PSP symptoms for less than 5 years
* Participant is able to walk 5 steps with minimal assistance (stabilization of one arm or use of cane/walker)
* Participant has an identified, reliable, study partner (e.g., caregiver, family member, social worker, or friend)

Key Exclusion Criteria:

* Participants who weigh less than 44 kg (97 lbs) at screening
* Mini-Mental State Examination (MMSE) score less than 15 at screening
* Any contraindication or inability to tolerate brain magnetic resonance imaging (MRI)
* Participant resides at a skilled nursing or dementia care facility, or admission to such a facility is planned during the study period
* Evidence of any clinically significant neurological disorder other than PSP
* The participant has a history of or currently has schizophrenia, schizoaffective disorder or bipolar disorder according to Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V) or International Classification of Diseases (ICD-10) criteria
* Participant has had a significant illness or infection requiring medical intervention in the past 30 days

Primary outcomes:
measure: Change From Baseline to Week 52 in Progressive Supranuclear Palsy Rating Scale (PSPRS) Total Score
timeFrame: Baseline, Week 52
measure: Number of Participants With Adverse Events
timeFrame: From the first dose of study drug until 20 weeks following discontinuation of study drug administration have elapsed (approximately 5 half-lives), up to 80 weeks
Secondary outcomes:
measure: Mean Change From Baseline to Week 52 in Unified Parkinson's Disease Rating Scale (UPDRS) Part II (Activities of Daily Living)
timeFrame: Baseline, Week 52
measure: Clinical Global Impression of Change (CGI-C) Score at Week 52
timeFrame: Week 52
measure: Mean Change From Baseline to Week 52 in Midbrain Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI)
timeFrame: Baseline, Week 52
measure: Mean Change From Baseline to Week 52 in Schwab and England Activities of Daily Living Scale (SEADL)
timeFrame: Baseline, Week 52
measure: Maximum Observed Serum Concentration (Cmax) for ABBV-8E12
timeFrame: First Dosing Interval, 2 weeks, Day 1-14; Fifth Dosing Interval, 4 weeks, Day 85-113
measure: Time to Maximum Observed Serum Concentration (Tmax) for ABBV-8E12
timeFrame: First Dosing Interval, 2 weeks, Day 1-14; Fifth Dosing Interval, 4 weeks, Day 85-113
measure: Area Under the Concentration Time Curve (AUC) for ABBV-8E12
timeFrame: First Dosing Interval, 2 weeks, Day 1-14; Fifth Dosing Interval, 4 weeks, Day 85-113
measure: Serum Concentration of ABBV-8E12 Prior to Infusion of a Day of Dosing (Ctrough)
timeFrame: First day of the Fifth Dosing Interval, Day 85
measure: Mean Change From Baseline to Week 52 in Clinical Global Impression of Severity (CGI-S) Score
timeFrame: Baseline, Week 52
measure: Mean Change From Baseline to Week 52 in Progressive Supranuclear Palsy Health Related Quality of Life Scale (PSP-QoL) Total Score
timeFrame: Baseline, Week 52
measure: Mean Change From Baseline to Week 52 in Progressive Supranuclear Palsy Staging System Score (PSP-SS) Score
timeFrame: Baseline, Week 52
measure: Mean Change From Baseline to Week 52 in Third Ventricle Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI)
timeFrame: Baseline, Week 52
measure: Mean Change From Baseline to Week 52 in Superior Cerebellar Peduncle Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI)
timeFrame: Baseline, Week 52
measure: Mean Change From Baseline to Week 52 in Brainstem Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI)
timeFrame: Baseline, Week 52
measure: Mean Change From Baseline to Week 52 in Whole Brain Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI)
timeFrame: Baseline, Week 52
measure: Mean Change From Baseline to Week 52 in Frontal Lobe Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI)
timeFrame: Baseline, Week 52
measure: Time to Loss of Ability to Walk Independently as Measured by Progressive Supranuclear Palsy Rating Scale (PSPRS) Item 26
timeFrame: From Baseline to Week 52
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham - Main /ID# 144892
state: Alabama
city: Scottsdale
country: United States
facility: Mayo Clinic - Scottsdale /ID# 144893
state: Arizona
city: Beverly Hills
country: United States
facility: Cedars-Sinai Medical Center /ID# 149775
state: California
city: La Jolla
country: United States
facility: Ucsd /Id# 144905
state: California
city: Los Angeles
country: United States
facility: Usc /Id# 149773
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles /ID# 144896
state: California
city: San Francisco
country: United States
facility: Univ California, San Francisco /ID# 144897
state: California
city: Englewood
country: United States
facility: Rocky Mountain Movement Disorders Center /ID# 153397
state: Colorado
city: Gainesville
country: United States
facility: University of Florida - Archer /ID# 144906
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic /ID# 144911
state: Florida
city: Tampa
country: United States
facility: University of South Florida /ID# 144912
state: Florida
city: Augusta
country: United States
facility: Georgia Regents University /ID# 144908
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center /ID# 144894
state: Illinois
city: Chicago
country: United States
facility: University of Chicago /ID# 148672
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University /ID# 149036
state: Indiana
city: Lexington
country: United States
facility: University of Kentucky Chandler Medical Center /ID# 144891
state: Kentucky
city: Rochester
country: United States
facility: Mayo Clinic - Rochester /ID# 144895
state: Minnesota
city: Kansas City
country: United States
facility: St. Luke's Hosp. of Kansas Cit /ID# 168629
state: Missouri
city: Las Vegas
country: United States
facility: Cleveland Clinic Lou Ruvo Cent /ID# 148919
state: Nevada
city: New Brunswick
country: United States
facility: Rutgers Robert Wood Johnson /ID# 144901
state: New Jersey
city: New York
country: United States
facility: COLUMBIA University Medical Center /ID# 149037
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Main Campus /ID# 144885
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University /ID# 149774
state: Oregon
city: Nashville
country: United States
facility: Vanderbilt Univ Med Ctr /ID# 144898
state: Tennessee
city: Dallas
country: United States
facility: Kerwin Research Center /ID# 144904
state: Texas
city: Houston
country: United States
facility: McGovern Medical School /ID# 149236
state: Texas
city: Round Rock
country: United States
facility: Central Texas Neurology Consul /ID# 167417
state: Texas
city: Westmead
country: Australia
facility: Westmead Hospital /ID# 154403
state: New South Wales
city: Herston
country: Australia
facility: Q-Pharm Pty Limited /ID# 154410
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital /ID# 153157
state: South Australia
city: Melbourne
country: Australia
facility: Alfred Hospital /ID# 153158
state: Victoria
city: West Perth
country: Australia
facility: Neurodegenerative Disorders Re /ID# 153770
state: Western Australia
city: Calgary
country: Canada
facility: University of Calgary /ID# 154393
state: Alberta
city: Kelowna
country: Canada
facility: OCT Research ULC /ID# 169688
state: British Columbia
city: Toronto
country: Canada
facility: Toronto Western Hospital /ID# 152818
state: Ontario
city: Montreal
country: Canada
facility: Crchum /Id# 152819
state: Quebec
city: Montreal
country: Canada
facility: Montreal Neurological Institut /ID# 156413
state: Quebec
city: Toulouse
country: France
facility: Hopital Universitaire Purpan /ID# 153152
state: Haute-Garonne
city: Marseille CEDEX 05
country: France
facility: Hopital de la Timone /ID# 153113
state: Provence-Alpes-Cote-d Azur
city: Bordeaux
country: France
facility: Chu de Bordeaux Hopital /Id# 153151
city: Lille
country: France
facility: Hopital B Roger Salengro /ID# 153943
city: Paris
country: France
facility: Hopital Pitie Salpetriere /ID# 153942
city: Strasbourg
country: France
facility: CHU Strasbourg Hautepierre Hos /ID# 206942
city: Bochum
country: Germany
facility: St. Josef-Hospital /ID# 201984
state: Nordrhein-Westfalen
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig /ID# 201761
state: Sachsen
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm /ID# 153155
state: Thueringen
city: Hausham
country: Germany
facility: KH Agatharied /ID# 154166
city: Munich
country: Germany
facility: TU Uniklinik Munchen /ID# 153154
city: Catanzaro
country: Italy
facility: Universita di Catanzaro Magna Graecia /ID# 166322
state: Calabria
city: Rome
country: Italy
facility: Policlinico Agostino Gemelli /ID# 153104
state: Lazio
city: Rozzano
country: Italy
facility: IBD Center - IRCCS Istituto Clinico Humanitas /ID# 155092
state: Milano
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Neurologico Carlo Besta /ID# 201982
city: Pozzilli
country: Italy
facility: Istituto Neuro Mediterraneo IR /ID# 153106
city: Terni
country: Italy
facility: A.O. Santa Maria /ID# 153102
city: Venezia LIDO
country: Italy
facility: IRCCS Ospedale San Camillo /ID# 153101
city: Nagoya-shi
country: Japan
facility: National Hospital Organization Higashinagoya National Hospital /ID# 201514
state: Aichi
city: Asahikawa
country: Japan
facility: National Hospital Organization Asahikawa Medical Center /ID# 201585
state: Hokkaido
city: Kyoto City
country: Japan
facility: National Hospital Organization Utano National Hospital /ID# 201979
state: Kyoto
city: Sendai-shi
country: Japan
facility: Tohoku University Hospital /ID# 202307
state: Miyagi
city: Sendai
country: Japan
facility: NHO Sendai Nishitaga National Hospital /ID# 202132
state: Miyagi
city: Niigata-shi
country: Japan
facility: Niigata University Medical & Dental Hospital /ID# 201680
state: Niigata
city: Suita-shi
country: Japan
facility: Osaka University Hospital /ID# 201980
state: Osaka
city: Bunkyo-ku
country: Japan
facility: Juntendo University Hospital /ID# 200870
state: Tokyo
city: Kodaira
country: Japan
facility: National Center of Neurology and Psychiatry /ID# 202037
state: Tokyo
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon /ID# 200876
city: Sevilla
country: Spain
facility: Hosp Univ Virgen del Rocio /ID# 201039
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References:
citation: Hoglinger GU, Litvan I, Mendonca N, Wang D, Zheng H, Rendenbach-Mueller B, Lon HK, Jin Z, Fisseha N, Budur K, Gold M, Ryman D, Florian H; Arise Investigators. Safety and efficacy of tilavonemab in progressive supranuclear palsy: a phase 2, randomised, placebo-controlled trial. Lancet Neurol. 2021 Mar;20(3):182-192. doi: 10.1016/S1474-4422(20)30489-0.