A Study to Assess Efficacy, Safety, Tolerability, and Pharmacokinetics of ABBV-8E12 in Subjects With Progressive Supranuclear Palsy (PSP)
- Conditions
- Progressive Supranuclear Palsy
- Interventions
- Drug: PlaceboDrug: ABBV-8E12
- Registration Number
- NCT02985879
- Lead Sponsor
- AbbVie
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 378
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo 0.9% Sodium Chloride Injection/Solution for Infusion; intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks ABBV-8E12 2000 mg ABBV-8E12 Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain) ABBV-8E12 4000 mg ABBV-8E12 Intravenous infusions at Day 1, Day 15, and Day 29, then every 28 days for 52 weeks; 300 mg/15 mL (participants in countries other than Japan or Spain); 1000 mg/10 mL (for participants in Japan or Spain)
- Primary Outcome Measures
Name Time Method Change From Baseline to Week 52 in Progressive Supranuclear Palsy Rating Scale (PSPRS) Total Score 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 changes in score indicate worsening from baseline.
Number of Participants With Adverse Events 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 An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each event to the use of study drug as either reasonable possibility or no reasonable possibility. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the subject and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent events (TEAEs) are defined as any event that began or worsened in severity from first dose of study drug until 20 weeks after the last dose. For more details on AEs please see the Adverse Event section.
- Secondary Outcome Measures
Name Time Method Mean Change From Baseline to Week 52 in Midbrain Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI) Baseline, Week 52 Magnetic resonance imaging (MRI) of several different brain regions was performed and volumetric analysis was conducted to quantify midbrain atrophy. Negative changes in values indicate a reduction in volume.
Maximum Observed Serum Concentration (Cmax) for ABBV-8E12 First Dosing Interval, 2 weeks, Day 1-14; Fifth Dosing Interval, 4 weeks, Day 85-113 The maximum observed serum concentration after the first and the fifth doses in Cohort 1 and Cohort J1 was determined.
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 changes in score indicate worsening from baseline.
Mean Change From Baseline to Week 52 in Superior Cerebellar Peduncle Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI) Baseline, Week 52 Magnetic resonance imaging (MRI) of several different brain regions was performed and volumetric analysis was conducted to quantify Superior cerebellar peduncle atrophy. Negative changes in values indicate a reduction in volume.
Mean Change From Baseline to Week 52 in Brainstem Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI) Baseline, Week 52 Magnetic resonance imaging (MRI) of several different brain regions was performed and volumetric analysis was conducted to quantify brainstem atrophy. Negative changes in values indicate a reduction in volume.
Mean Change From Baseline to Week 52 in Whole Brain Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI) Baseline, Week 52 Magnetic resonance imaging (MRI) of several different brain regions was performed and volumetric analysis was conducted to quantify whole brain atrophy. Negative changes in values indicate a reduction in volume.
Mean Change From Baseline to Week 52 in Frontal Lobe Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI) Baseline, Week 52 Magnetic resonance imaging (MRI) of several different brain regions was performed and volumetric analysis was conducted to quantify frontal lobe atrophy. Positive changes in values indicate an increase in volume.
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 changes in score indicate worsening from baseline.
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) 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 changes in values indicate a decline in health.
Area Under the Concentration Time Curve (AUC) for ABBV-8E12 First Dosing Interval, 2 weeks, Day 1-14; Fifth Dosing Interval, 4 weeks, Day 85-113 The area under the plasma concentration-time curve (AUC; measured in µg•day/mL) is a method of measurement to determine the total exposure of a drug in blood plasma. The AUC24 of ABBV-8E12 was estimated using non-compartmental methods after the first and the fifth doses in Cohort 1 and Cohort J1.
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 changes in score indicate worsening from baseline.
Mean Change From Baseline to Week 52 in Progressive Supranuclear Palsy Health Related Quality of Life Scale (PSP-QoL) Total Score Baseline, Week 52 The PSP-QoL is a validated patient-reported outcome measure, specifically designed to assess the quality of life of participants with PSP. There are 45 items and two subscales: physical and mental impact. Items are scored from 0 (no problem) to 4 (extreme problems). The total subscale sum scores are linearly converted into a 0 to 100 scale, and higher scores indicate a lower quality of life. Positive changes in score indicate a decline in quality of life.
Clinical Global Impression of Change (CGI-C) Score at Week 52 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.
Time to Maximum Observed Serum Concentration (Tmax) for ABBV-8E12 First Dosing Interval, 2 weeks, Day 1-14; Fifth Dosing Interval, 4 weeks, Day 85-113 The time to maximum plasma concentration (Tmax; measured in hours) is the time it takes for a drug to achieve Cmax, the maximum plasma concentration. Tmax was measured after the first and the fifth doses in Cohort 1 and Cohort J1.
Mean Change From Baseline to Week 52 in Third Ventricle Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI) Baseline, Week 52 Magnetic resonance imaging (MRI) of several different brain regions was performed and volumetric analysis was conducted to quantify third ventricle atrophy. Positive changes in values indicate an increase in volume.
Serum Concentration of ABBV-8E12 Prior to Infusion of a Day of Dosing (Ctrough) First day of the Fifth Dosing Interval, Day 85 The concentration of ABBV-8E12 immediately prior to infusion of the fifth dose (Ctrough; measured in µg/mL) was estimated using non-compartmental methods in Cohort 1 and Cohort J1.
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 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. 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 (66)
Usc /Id# 149773
🇺🇸Los Angeles, California, United States
Mayo Clinic - Scottsdale /ID# 144893
🇺🇸Scottsdale, Arizona, United States
Ucsd /Id# 144905
🇺🇸La Jolla, California, United States
Rocky Mountain Movement Disorders Center /ID# 153397
🇺🇸Englewood, Colorado, United States
Oregon Health and Science University /ID# 149774
🇺🇸Portland, Oregon, United States
Hospital General Universitario Gregorio Maranon /ID# 200876
🇪🇸Madrid, Spain
Hosp Univ Virgen del Rocio /ID# 201039
🇪🇸Sevilla, Spain
University of Alabama at Birmingham - Main /ID# 144892
🇺🇸Birmingham, Alabama, United States
Univ California, San Francisco /ID# 144897
🇺🇸San Francisco, California, United States
Indiana University /ID# 149036
🇺🇸Indianapolis, Indiana, United States
Cleveland Clinic Lou Ruvo Cent /ID# 148919
🇺🇸Las Vegas, Nevada, United States
Vanderbilt Univ Med Ctr /ID# 144898
🇺🇸Nashville, Tennessee, United States
OCT Research ULC /ID# 169688
🇨🇦Kelowna, British Columbia, Canada
National Center of Neurology and Psychiatry /ID# 202037
🇯🇵Kodaira, Tokyo, Japan
Universita di Catanzaro Magna Graecia /ID# 166322
🇮🇹Catanzaro, Calabria, Italy
Hopital Universitaire Purpan /ID# 153152
🇫🇷Toulouse, Haute-Garonne, France
Universitaetsklinikum Leipzig /ID# 201761
🇩🇪Leipzig, Sachsen, Germany
Cedars-Sinai Medical Center /ID# 149775
🇺🇸Beverly Hills, California, United States
University of Florida - Archer /ID# 144906
🇺🇸Gainesville, Florida, United States
University of California, Los Angeles /ID# 144896
🇺🇸Los Angeles, California, United States
Rush University Medical Center /ID# 144894
🇺🇸Chicago, Illinois, United States
University of Kentucky Chandler Medical Center /ID# 144891
🇺🇸Lexington, Kentucky, United States
St. Luke's Hosp. of Kansas Cit /ID# 168629
🇺🇸Kansas City, Missouri, United States
COLUMBIA University Medical Center /ID# 149037
🇺🇸New York, New York, United States
Kerwin Research Center /ID# 144904
🇺🇸Dallas, Texas, United States
Central Texas Neurology Consul /ID# 167417
🇺🇸Round Rock, Texas, United States
Q-Pharm Pty Limited /ID# 154410
🇦🇺Herston, Queensland, Australia
Westmead Hospital /ID# 154403
🇦🇺Westmead, New South Wales, Australia
Alfred Hospital /ID# 153158
🇦🇺Melbourne, Victoria, Australia
Royal Adelaide Hospital /ID# 153157
🇦🇺Adelaide, South Australia, Australia
Neurodegenerative Disorders Re /ID# 153770
🇦🇺West Perth, Western Australia, Australia
Crchum /Id# 152819
🇨🇦Montreal, Quebec, Canada
Toronto Western Hospital /ID# 152818
🇨🇦Toronto, Ontario, Canada
Montreal Neurological Institut /ID# 156413
🇨🇦Montreal, Quebec, Canada
Hopital de la Timone /ID# 153113
🇫🇷Marseille CEDEX 05, Provence-Alpes-Cote-d Azur, France
Hopital B Roger Salengro /ID# 153943
🇫🇷Lille, France
Hopital Pitie Salpetriere /ID# 153942
🇫🇷Paris, France
Chu de Bordeaux Hopital /Id# 153151
🇫🇷Bordeaux, France
CHU Strasbourg Hautepierre Hos /ID# 206942
🇫🇷Strasbourg, France
St. Josef-Hospital /ID# 201984
🇩🇪Bochum, Nordrhein-Westfalen, Germany
Policlinico Agostino Gemelli /ID# 153104
🇮🇹Rome, Lazio, Italy
IBD Center - IRCCS Istituto Clinico Humanitas /ID# 155092
🇮🇹Rozzano, Milano, Italy
Universitaetsklinikum Ulm /ID# 153155
🇩🇪Ulm, Thueringen, Germany
KH Agatharied /ID# 154166
🇩🇪Hausham, Germany
Fondazione IRCCS Istituto Neurologico Carlo Besta /ID# 201982
🇮🇹Milan, Italy
Istituto Neuro Mediterraneo IR /ID# 153106
🇮🇹Pozzilli, Italy
A.O. Santa Maria /ID# 153102
🇮🇹Terni, Italy
IRCCS Ospedale San Camillo /ID# 153101
🇮🇹Venezia LIDO, Italy
National Hospital Organization Higashinagoya National Hospital /ID# 201514
🇯🇵Nagoya-shi, Aichi, Japan
National Hospital Organization Asahikawa Medical Center /ID# 201585
🇯🇵Asahikawa, Hokkaido, Japan
National Hospital Organization Utano National Hospital /ID# 201979
🇯🇵Kyoto City, Kyoto, Japan
Tohoku University Hospital /ID# 202307
🇯🇵Sendai-shi, Miyagi, Japan
Osaka University Hospital /ID# 201980
🇯🇵Suita-shi, Osaka, Japan
Niigata University Medical & Dental Hospital /ID# 201680
🇯🇵Niigata-shi, Niigata, Japan
Juntendo University Hospital /ID# 200870
🇯🇵Bunkyo-ku, Tokyo, Japan
NHO Sendai Nishitaga National Hospital /ID# 202132
🇯🇵Sendai, Miyagi, Japan
Cleveland Clinic Main Campus /ID# 144885
🇺🇸Cleveland, Ohio, United States
Rutgers Robert Wood Johnson /ID# 144901
🇺🇸New Brunswick, New Jersey, United States
TU Uniklinik Munchen /ID# 153154
🇩🇪Munich, Germany
University of Chicago /ID# 148672
🇺🇸Chicago, Illinois, United States
University of South Florida /ID# 144912
🇺🇸Tampa, Florida, United States
Mayo Clinic /ID# 144911
🇺🇸Jacksonville, Florida, United States
Georgia Regents University /ID# 144908
🇺🇸Augusta, Georgia, United States
McGovern Medical School /ID# 149236
🇺🇸Houston, Texas, United States
University of Calgary /ID# 154393
🇨🇦Calgary, Alberta, Canada
Mayo Clinic - Rochester /ID# 144895
🇺🇸Rochester, Minnesota, United States