An Extension Study of ABBV-8E12 in Progressive Supranuclear Palsy (PSP)
- Conditions
- Progressive Supranuclear Palsy (PSP)
- Interventions
- Drug: ABBV-8E12Drug: Placebo solution for IV infusion on Day 15
- Registration Number
- NCT03391765
- Lead Sponsor
- AbbVie
- Brief Summary
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).
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 142
- 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)
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description M15-562 ABBV-8E12 2000 mg/M15-563 ABBV-8E12 2000 mg ABBV-8E12 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). M15-562 ABBV-8E12 2000 mg/M15-563 ABBV-8E12 2000 mg Placebo solution for IV infusion on Day 15 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). M15-562 ABBV-8E12 4000 mg/M15-563 ABBV-8E12 4000 mg ABBV-8E12 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). M15-562 ABBV-8E12 4000 mg/M15-563 ABBV-8E12 4000 mg Placebo solution for IV infusion on Day 15 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). M15-562 Placebo/M15-563 ABBV-8E12 2000 mg ABBV-8E12 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. M15-562 Placebo/M15-563 ABBV-8E12 4000 mg ABBV-8E12 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.
- Primary Outcome Measures
Name Time Method Change in Progressive Supranuclear Palsy Rating Scale (PSPRS) Total Score From Baseline to Week 52 Baseline, 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.
- Secondary Outcome Measures
Name Time Method Mean Change From Baseline to Week 52 in Unified Parkinson's Disease Rating Scale (UPDRS) Part II (Activities of Daily Living) Baseline, Week 52 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.
Change in Clinical Global Impression of Severity (CGI-C) Score From Baseline to Week 52 Baseline, 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.
Mean Change From Baseline to Week 52 in Schwab and England Activities of Daily Living Scale (SEADL) Baseline, Week 52 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.
Mean Change From Baseline to Week 52 in Clinical Global Impression of Severity (CGI-S) Score Baseline, Week 52 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.
Patient Global Impression of Change Score (PGI-C) Score From Baseline to Week 52 Baseline, 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.
Mean Change From Baseline to Week 52 in Progressive Supranuclear Palsy Staging System Score (PSP-SS) Score Baseline, Week 52 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.
Time to Loss of Ability to Walk Independently as Measured by Progressive Supranuclear Palsy Rating Scale (PSPRS) Item 26 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 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).
Trial Locations
- Locations (42)
Usc /Id# 165529
🇺🇸Los Angeles, California, United States
University of California, Los Angeles /ID# 165669
🇺🇸Los Angeles, California, United States
IRCCS San Camillo /ID# 201229
🇮🇹Venice, Italy
Cedars-Sinai Medical Center /ID# 165567
🇺🇸Beverly Hills, California, United States
Kerwin Research Center /ID# 206872
🇺🇸Dallas, Texas, United States
A.O. Santa Maria /ID# 165535
🇮🇹Terni, Italy
CHUM - Notre-Dame Hospital /ID# 165461
🇨🇦Montréal, Quebec, Canada
Rocky Mountain Movement Disorders Center /ID# 165559
🇺🇸Englewood, Colorado, United States
Augusta University Medical Center /ID# 165562
🇺🇸Augusta, Georgia, United States
University of Kentucky Chandler Medical Center /ID# 165566
🇺🇸Lexington, Kentucky, United States
Columbia Univ Medical Center /ID# 165528
🇺🇸New York, New York, United States
National Center of Neurology and Psychiatry /ID# 208820
🇯🇵Kodaira, Tokyo, Japan
Royal Adelaide Hospital /ID# 165451
🇦🇺Adelaide, South Australia, Australia
Osaka University Hospital /ID# 208787
🇯🇵Suita-shi, Osaka, Japan
University of Catanzaro /ID# 170214
🇮🇹Catanzaro, Italy
National Hospital Organization Asahikawa Medical Center /ID# 208818
🇯🇵Asahikawa, Hokkaido, Japan
Cleveland Clinic Lou Ruvo Cent /ID# 165538
🇺🇸Las Vegas, Nevada, United States
Univ Alabama-Birmingham /ID# 165522
🇺🇸Birmingham, Alabama, United States
University of California, San /ID# 165560
🇺🇸San Diego, California, United States
Rush University Medical Center /ID# 165527
🇺🇸Chicago, Illinois, United States
Indiana University /ID# 165519
🇺🇸Indianapolis, Indiana, United States
Univ California, San Francisco /ID# 165553
🇺🇸San Francisco, California, United States
Cleveland Clinic Main Campus /ID# 165537
🇺🇸Cleveland, Ohio, United States
Vanderbilt Univ Med Ctr /ID# 165520
🇺🇸Nashville, Tennessee, United States
McGovern Medical School /ID# 165565
🇺🇸Houston, Texas, United States
Mayo Clinic Arizona /ID# 165521
🇺🇸Phoenix, Arizona, United States
UF Center for Movement Disorde /ID# 165561
🇺🇸Gainesville, Florida, United States
Mayo Clinic /ID# 165554
🇺🇸Jacksonville, Florida, United States
Rutgers Robert Wood Johnson /ID# 165526
🇺🇸New Brunswick, New Jersey, United States
Montreal Neurological Institut /ID# 165546
🇨🇦Montreal, Quebec, Canada
Policlinico Agostino Gemelli /ID# 165536
🇮🇹Rome, Lazio, Italy
Istituto Neuro Mediterraneo IR /ID# 165533
🇮🇹Pozzilli, Italy
National Hospital Organization Utano National Hospital /ID# 208780
🇯🇵Kyoto City, Kyoto, Japan
University of South Florida /ID# 165556
🇺🇸Tampa, Florida, United States
University of Chicago Medical /ID# 165555
🇺🇸Chicago, Illinois, United States
Alfred Hospital /ID# 165454
🇦🇺Melbourne, Victoria, Australia
National Hospital Organization Higashinagoya National Hospital /ID# 208786
🇯🇵Nagoya-shi, Aichi, Japan
University of Calgary /ID# 165667
🇨🇦Calgary, Alberta, Canada
Q-Pharm Pty Limited /ID# 165452
🇦🇺Herston, Queensland, Australia
Mayo Clinic - Rochester /ID# 165518
🇺🇸Rochester, Minnesota, United States
Toronto Western Hospital /ID# 165462
🇨🇦Toronto, Ontario, Canada
NHO Sendai Nishitaga National Hospital /ID# 209014
🇯🇵Sendai, Miyagi, Japan