An Extension Study of ABBV-8E12 in Progressive Supranuclear Palsy (PSP)

The purpose of this study was to assess the long-term safety and efficacy of ABBV-8E12 (tilavonemab) in participants with progressive supranuclear palsy (PSP).

Study Overview

• Status: Terminated
• Conditions: Progressive Supranuclear Palsy (PSP)
• Intervention / Treatment: Drug: ABBV-8E12; Drug: Placebo solution for IV infusion on Day 15

Detailed Description

This study (M15-563) was a Phase 2, randomized, double-blind, multiple-dose, multicenter, long-term extension of NCT 02985879 (Study M15-562) in participants with progressive supranuclear palsy (PSP). Those who completed the 52-week Treatment Period in Study M15-562 and met all entry criteria were eligible for enrollment into this study. This study planned for a Treatment Period of up to 5 years and a post-treatment follow-up visit approximately 20 weeks after the last dose of study drug (including participants who prematurely discontinued treatment). All participants received ABBV-8E12 as follows: those who received placebo in Study M15-562 were randomized, in a 1:1 ratio, to either 2000 or 4000 mg; those who received ABBV-8E12 at a dose of either 2000 or 4000 mg in Study M15-562 continued on the same dose in this study.

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

• Study Type: Interventional
• Enrollment (Actual): 142
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Herston, Queensland, Australia, 4006
      • Q-Pharm Pty Limited /ID# 165452
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital /ID# 165451
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Alfred Hospital /ID# 165454
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • University of Calgary /ID# 165667
  • Ontario
    • Toronto, Ontario, Canada, M5T 2S8
      • Toronto Western Hospital /ID# 165462
  • Quebec
    • Montreal, Quebec, Canada, H3A 2B4
      • Montreal Neurological Institut /ID# 165546
    • Montréal, Quebec, Canada, H2X 0A9
      • CHUM - Notre-Dame Hospital /ID# 165461
• Italy
  • Catanzaro, Italy, 88100
    • University of Catanzaro /ID# 170214
  • Pozzilli, Italy, 86077
    • Istituto Neuro Mediterraneo IR /ID# 165533
  • Terni, Italy, 05100
    • A.O. Santa Maria /ID# 165535
  • Venice, Italy, 30126
    • IRCCS San Camillo /ID# 201229
  • Lazio
    • Rome, Lazio, Italy, 00168
      • Policlinico Agostino Gemelli /ID# 165536
• Japan
  • Aichi
    • Nagoya-shi, Aichi, Japan, 4658620
      • National Hospital Organization Higashinagoya National Hospital /ID# 208786
  • Hokkaido
    • Asahikawa, Hokkaido, Japan, 070-8644
      • National Hospital Organization Asahikawa Medical Center /ID# 208818
  • Kyoto
    • Kyoto City, Kyoto, Japan, 616-8255
      • National Hospital Organization Utano National Hospital /ID# 208780
  • Miyagi
    • Sendai, Miyagi, Japan, 982-8555
      • NHO Sendai Nishitaga National Hospital /ID# 209014
  • Osaka
    • Suita-shi, Osaka, Japan, 565-0871
      • Osaka University Hospital /ID# 208787
  • Tokyo
    • Kodaira, Tokyo, Japan, 187-8551
      • National Center of Neurology and Psychiatry /ID# 208820
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Univ Alabama-Birmingham /ID# 165522
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Arizona /ID# 165521
  • California
    • Beverly Hills, California, United States, 90211
      • Cedars-Sinai Medical Center /ID# 165567
    • Los Angeles, California, United States, 90033
      • Usc /Id# 165529
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles /ID# 165669
    • San Diego, California, United States, 92037
      • University of California, San /ID# 165560
    • San Francisco, California, United States, 94143-2204
      • Univ California, San Francisco /ID# 165553
  • Colorado
    • Englewood, Colorado, United States, 80113-2736
      • Rocky Mountain Movement Disorders Center /ID# 165559
  • Florida
    • Gainesville, Florida, United States, 32607
      • UF Center for Movement Disorde /ID# 165561
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic /ID# 165554
    • Tampa, Florida, United States, 33612
      • University of South Florida /ID# 165556
  • Georgia
    • Augusta, Georgia, United States, 30912-0004
      • Augusta University Medical Center /ID# 165562
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center /ID# 165527
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical /ID# 165555
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University /ID# 165519
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky Chandler Medical Center /ID# 165566
  • Minnesota
    • Rochester, Minnesota, United States, 55905-0001
      • Mayo Clinic - Rochester /ID# 165518
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Cleveland Clinic Lou Ruvo Cent /ID# 165538
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers Robert Wood Johnson /ID# 165526
  • New York
    • New York, New York, United States, 10032-3725
      • Columbia Univ Medical Center /ID# 165528
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Main Campus /ID# 165537
  • Tennessee
    • Nashville, Tennessee, United States, 37232-0011
      • Vanderbilt Univ Med Ctr /ID# 165520
  • Texas
    • Dallas, Texas, United States, 75231-4316
      • Kerwin Research Center /ID# 206872
    • Houston, Texas, United States, 77054
      • McGovern Medical School /ID# 165565

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participant completed the 52-week treatment period in Study M15-562 (NCT02985879)
• In the opinion of the investigator, the participant was compliant during participation in Study M15-562 (NCT02985879)
• Participant has an identified, reliable, study partner (e.g., caregiver, family member, social worker, or friend)

Exclusion Criteria:

• Participants who weigh less than 44 kg (97 lbs) at the time of study entry
• Any contraindication or inability to tolerate brain magnetic resonance imaging (MRI)
• Participant has any significant change in his/her medical condition that could interfere with the subject's participation in the study, could place the subject at increased risk, or could confound interpretation of study results
• More than 8 weeks have elapsed since the participant received his/her last dose of study drug in Study M15-562 (NCT02985879)
• Participant is considered by the investigator, for any reason, to be an unsuitable candidate to receive ABBV-8E12 or the participant is considered by the investigator to be unable or unlikely to comply with the dosing schedule or study evaluations

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: M15-562 ABBV-8E12 2000 mg/M15-563 ABBV-8E12 2000 mg; Intravenous (IV) infusions of 2000 mg ABBV-8E12 at Day 1 and Day 29, then every 28 days for up to 5 years; administered at 300 mg/15 mL and 1000 mg/10 mL strength. Placebo IV infusion was administered on Day 15 in Study M15-563 (to maintain the blind in Study M15-562).	Drug: ABBV-8E12; Participants with 44-49 kg body weight (BW) had an intravenous infusion rate of 3.5 mL/min or 210 mL/hr; those with 50-58 kg BW, 4.0 mL/min or 240 mL/hr; and those with a BW >59 kg, 4.7 mL/min or 282 mL/hr.; Other Names: Tilavonemab; Drug: Placebo solution for IV infusion on Day 15; 0.9% NaCl injection/solution for infusion 500 mL; participants with 44-49 kg body weight (BW) had an intravenous infusion rate of 3.5 mL/min or 210 mL/hr; those with 50-58 kg BW, 4.0 mL/min or 240 mL/hr; and those with a BW >59 kg, 4.7 mL/min or 282 mL/hr.
Experimental: M15-562 ABBV-8E12 4000 mg/M15-563 ABBV-8E12 4000 mg; Intravenous (IV) infusions of 4000 mg ABBV-8E12 at Day 1 and Day 29, then every 28 days for up to 5 years; administered at 300 mg/15 mL and 1000 mg/10 mL strength. Placebo IV infusion was administered on Day 15 in Study M15-563 (to maintain the blind in Study M15-562).	Drug: ABBV-8E12; Participants with 44-49 kg body weight (BW) had an intravenous infusion rate of 3.5 mL/min or 210 mL/hr; those with 50-58 kg BW, 4.0 mL/min or 240 mL/hr; and those with a BW >59 kg, 4.7 mL/min or 282 mL/hr.; Other Names: Tilavonemab; Drug: Placebo solution for IV infusion on Day 15; 0.9% NaCl injection/solution for infusion 500 mL; participants with 44-49 kg body weight (BW) had an intravenous infusion rate of 3.5 mL/min or 210 mL/hr; those with 50-58 kg BW, 4.0 mL/min or 240 mL/hr; and those with a BW >59 kg, 4.7 mL/min or 282 mL/hr.
Experimental: M15-562 Placebo/M15-563 ABBV-8E12 2000 mg; Intravenous (IV) infusions of 2000 mg ABBV-8E12 at Day 1, Day 15, and Day 29, then every 28 days for up to 5 years; administered at 300 mg/15 mL and 1000 mg/10 mL strength.	Drug: ABBV-8E12; Participants with 44-49 kg body weight (BW) had an intravenous infusion rate of 3.5 mL/min or 210 mL/hr; those with 50-58 kg BW, 4.0 mL/min or 240 mL/hr; and those with a BW >59 kg, 4.7 mL/min or 282 mL/hr.; Other Names: Tilavonemab
Experimental: M15-562 Placebo/M15-563 ABBV-8E12 4000 mg; Intravenous (IV) infusions of 4000 mg ABBV-8E12 at Day 1, Day 15, and Day 29, then every 28 days for up to 5 years; administered at 300 mg/15 mL and 1000 mg/10 mL strength.	Drug: ABBV-8E12; Participants with 44-49 kg body weight (BW) had an intravenous infusion rate of 3.5 mL/min or 210 mL/hr; those with 50-58 kg BW, 4.0 mL/min or 240 mL/hr; and those with a BW >59 kg, 4.7 mL/min or 282 mL/hr.; Other Names: Tilavonemab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Progressive Supranuclear Palsy Rating Scale (PSPRS) Total Score From Baseline to Week 52	The PSPRS consists of 28 items grouped in six domains: daily activities (by history); behavior; bulbar; ocular motor; limb motor; and gait/midline. Items are scored on a 0 to 4 scale, except for six items that are scored on a 0 to 2 scale, with the total score ranging from 0 to 100. Higher scores indicate more severe disability or movement abnormality. Positive values indicate worsening from baseline.	Baseline, Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline to Week 52 in Unified Parkinson's Disease Rating Scale (UPDRS) Part II (Activities of Daily Living)	The Unified Parkinson's Disease Rating Scale (UPDRS) is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The Part II score is the sum of the answers to the 13 questions related to Activities of Daily Living, and ranges from 0-52. Higher scores are associated with more disability. Positive values indicate worsening from baseline.	Baseline, Week 52
Change in Clinical Global Impression of Severity (CGI-C) Score From Baseline to Week 52	The Clinical Global Impression of Change (CGI-C) score is a clinician's rating scale for assessing Global Improvement of Change. The CGI-C rates improvement by 7 categories: very much improved (1), much improved (2), minimally improved (3), no change (4), minimally worse (5), much worse (6), very much worse (7). The CGI-C score ranges from 1 to 7, with lower scores indicating improvement.	Baseline, Week 52
Mean Change From Baseline to Week 52 in Schwab and England Activities of Daily Living Scale (SEADL)	The Schwab and England Activities of Daily Living (SEADL) scale consists of ten items intended to evaluate the daily life activities of a participant. The SEADL is composed of two sections: the first is a self-reported questionnaire in which participants grade their own daily life activities, such as dressing, using the toilet, resting, eating, and social activities (subjective assessment), and the second is an assessment of motor functions, such as postural balance, speaking, rigidity, and tremors, conducted by a clinician (objective assessment). It is a percentage scale divided into deciles, and the results are reported between 0% (bedridden) and 100% (healthy). Negative values indicate worsening from baseline.	Baseline, Week 52
Mean Change From Baseline to Week 52 in Clinical Global Impression of Severity (CGI-S) Score	The CGI-S is a clinician's rating of disease severity. The CGI-S rates severity of illness on a 7-point scale, using a range of responses from 1 (normal) through 7 (the most severely ill). This rating is based upon observed and reported symptoms, behavior, and function in the past 7 days. Positive values indicate worsening from baseline.	Baseline, Week 52
Patient Global Impression of Change Score (PGI-C) Score From Baseline to Week 52	The PGI-C is a participant's rating of the change in their PSP-related symptoms since initiation of study drug. Participants rated their change in status using the following 7-point scale: 1 = Very much improved; 2 = Much improved; 3 = Minimally improved; 4 = No change; 5 = Minimally worse; 6 = Much worse; 7 = Very much worse.	Baseline, Week 52
Mean Change From Baseline to Week 52 in Progressive Supranuclear Palsy Staging System Score (PSP-SS) Score	The Progressive Supranuclear Palsy Rating Scale (PSPRS) consists of 28 items grouped in six domains: daily activities (by history); behavior; bulbar; ocular motor; limb motor; and gait/midline. Items are scored on a 0 to 4 scale, except for four items that are scored on a 0 to 2 scale, with the total score ranging from 0 to 100. Higher scores indicate more severe disability or movement abnormality. The PSP-SS score is a composite of the dysphagia and gait items from the PSPRS. Positive values indicate worsening from baseline.	Baseline, Week 52
Time to Loss of Ability to Walk Independently as Measured by Progressive Supranuclear Palsy Rating Scale (PSPRS) Item 26	The PSPRS consists of 28 items grouped in six domains: daily activities (by history); behavior; bulbar; ocular motor; limb motor; and gait/midline. Items are scored on a 0 to 4 scale, except for four items that are scored on a 0 to 2 scale, with the total score ranging from 0 to 100. Higher scores indicate more severe disability or movement abnormality. Item 26 pertains to gait, scored as either 0 (normal); 1 (slightly wide-based or irregular or slight pulsion on turns); 2 (must walk slowly or occasionally use walls or helper to avoid falling, especially on turns); 3 (must use assistance all or almost all the time); or 4 (unable to walk, even with walker; may be able to transfer).	From Baseline to Week 52

Collaborators and Investigators

• Sponsor: AbbVie

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2018
• Primary Completion (Actual): December 13, 2019
• Study Completion (Actual): December 13, 2019

Study Registration Dates

• First Submitted: January 2, 2018
• First Submitted That Met QC Criteria: January 2, 2018
• First Posted (Actual): January 5, 2018

Study Record Updates

• Last Update Posted (Actual): February 3, 2021
• Last Update Submitted That Met QC Criteria: February 1, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: PSP; Tauopathy; Steele-Richardson-Olszewski Syndrome
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Eye Diseases; Neurologic Manifestations; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Tauopathies; Cranial Nerve Diseases; Ocular Motility Disorders; Paralysis; Ophthalmoplegia; Supranuclear Palsy, Progressive; Nootropic Agents; Tilavonemab
• Other Study ID Numbers: M15-563; 2017-001590-16 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• IPD Sharing Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
• IPD Sharing Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No