Progressive Supranuclear PalsyPhase 2NCT02985879
A Study to Assess Efficacy, Safety, Tolerability, and Pharmacokinetics of ABBV-8E12 in Subjects With Progressive Supranuclear Palsy (PSP)
A Phase 2 study testing ABBV-8E12 in people with Progressive Supranuclear Palsy, run by AbbVie at 66 sites in 8 countries.
Trial summary
The purpose of this study was to assess efficacy, safety, tolerability, and pharmacokinetics of ABBV-8E12 in participants with progressive supranuclear palsy (PSP). Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Progressive Supranuclear Palsy
- What is being tested?
- ABBV-8E12
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 378 participants
- Where
- 66 sitesin 8 countries
- Study dates
- 12 Dec 2016to 20 Nov 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
66 sites in 8 countries.
66 sites in 8 countries
United States27 sites
Georgia Regents University /ID# 144908
Augusta, Georgia, 30912
Cedars-Sinai Medical Center /ID# 149775
Beverly Hills, California, 90211
University of Alabama at Birmingham - Main /ID# 144892
Birmingham, Alabama, 35233
Rush University Medical Center /ID# 144894
Chicago, Illinois, 60612
University of Chicago /ID# 148672
Chicago, Illinois, 60637-1443
Cleveland Clinic Main Campus /ID# 144885
Cleveland, Ohio, 44195
Kerwin Research Center /ID# 144904
Dallas, Texas, 75231-4316
Rocky Mountain Movement Disorders Center /ID# 153397
Englewood, Colorado, 80113-2736
University of Florida - Archer /ID# 144906
Gainesville, Florida, 32610
McGovern Medical School /ID# 149236
Houston, Texas, 77054
Indiana University /ID# 149036
Indianapolis, Indiana, 46202
Mayo Clinic /ID# 144911
Jacksonville, Florida, 32224
St. Luke's Hosp. of Kansas Cit /ID# 168629
Kansas City, Missouri, 64111
Ucsd /Id# 144905
La Jolla, California, 92093
Cleveland Clinic Lou Ruvo Cent /ID# 148919
Las Vegas, Nevada, 89106
University of Kentucky Chandler Medical Center /ID# 144891
Lexington, Kentucky, 40536
Usc /Id# 149773
Los Angeles, California, 90033
University of California, Los Angeles /ID# 144896
Los Angeles, California, 90095
Vanderbilt Univ Med Ctr /ID# 144898
Nashville, Tennessee, 37232-0011
Rutgers Robert Wood Johnson /ID# 144901
New Brunswick, New Jersey, 08901
COLUMBIA University Medical Center /ID# 149037
New York, New York, 10032-3725
Oregon Health and Science University /ID# 149774
Portland, Oregon, 97239
Mayo Clinic - Rochester /ID# 144895
Rochester, Minnesota, 55905-0001
Central Texas Neurology Consul /ID# 167417
Round Rock, Texas, 78681
Univ California, San Francisco /ID# 144897
San Francisco, California, 94143-2204
Mayo Clinic - Scottsdale /ID# 144893
Scottsdale, Arizona, 85259
University of South Florida /ID# 144912
Tampa, Florida, 33612
Japan9 sites
National Hospital Organization Asahikawa Medical Center /ID# 201585
Asahikawa, Hokkaido, 070-8644
Juntendo University Hospital /ID# 200870
Bunkyo-ku, Tokyo, 113-8431
National Center of Neurology and Psychiatry /ID# 202037
Kodaira, Tokyo, 187-8551
National Hospital Organization Utano National Hospital /ID# 201979
Kyoto, Kyoto, 616-8255
National Hospital Organization Higashinagoya National Hospital /ID# 201514
Nagoya, Aichi-ken, 4658620
Niigata University Medical & Dental Hospital /ID# 201680
Niigata, Niigata, 951-8520
Tohoku University Hospital /ID# 202307
Sendai, Miyagi, 980-8574
NHO Sendai Nishitaga National Hospital /ID# 202132
Sendai, Miyagi, 982-8555
Osaka University Hospital /ID# 201980
Suita-shi, Osaka, 565-0871
Italy7 sites
Universita di Catanzaro Magna Graecia /ID# 166322
Catanzaro, Calabria, 88100
Fondazione IRCCS Istituto Neurologico Carlo Besta /ID# 201982
Milan, 20133
Istituto Neuro Mediterraneo IR /ID# 153106
Pozzilli, 86077
Policlinico Agostino Gemelli /ID# 153104
Rome, Lazio, 00168
IBD Center - IRCCS Istituto Clinico Humanitas /ID# 155092
Rozzano, Milano, 20089
A.O. Santa Maria /ID# 153102
Terni, 05100
IRCCS Ospedale San Camillo /ID# 153101
Venezia LIDO, 30126
France6 sites
Chu de Bordeaux Hopital /Id# 153151
Bordeaux, 33076
Hopital B Roger Salengro /ID# 153943
Lille, 59037
Hopital de la Timone /ID# 153113
Marseille, Provence-Alpes-Côte d'Azur Region, 13385
Hopital Pitie Salpetriere /ID# 153942
Paris, 75651
CHU Strasbourg Hautepierre Hos /ID# 206942
Strasbourg, 67200
Hopital Universitaire Purpan /ID# 153152
Toulouse, Haute-Garonne, 31059
Australia5 sites
Royal Adelaide Hospital /ID# 153157
Adelaide, South Australia, 5000
Q-Pharm Pty Limited /ID# 154410
Herston, Queensland, 4006
Alfred Hospital /ID# 153158
Melbourne, Victoria, 3004
Neurodegenerative Disorders Re /ID# 153770
West Perth, Western Australia, 6005
Westmead Hospital /ID# 154403
Westmead, New South Wales, 2145
Canada5 sites
University of Calgary /ID# 154393
Calgary, Alberta, T2N 4Z6
OCT Research ULC /ID# 169688
Kelowna, British Columbia, V1Y 1Z9
Crchum /Id# 152819
Montreal, Quebec, H2X 0A9
Montreal Neurological Institut /ID# 156413
Montreal, Quebec, H3A 2B4
Toronto Western Hospital /ID# 152818
Toronto, Ontario, M5T 2S8
Germany5 sites
St. Josef-Hospital /ID# 201984
Bochum, North Rhine-Westphalia, 44791
KH Agatharied /ID# 154166
Hausham, 83734
Universitaetsklinikum Leipzig /ID# 201761
Leipzig, Saxony, 04103
TU Uniklinik Munchen /ID# 153154
Munich, 80802
Universitaetsklinikum Ulm /ID# 153155
Ulm, Thuringia, 89081
Spain2 sites
Hospital General Universitario Gregorio Maranon /ID# 200876
Madrid, 28007
Hosp Univ Virgen del Rocio /ID# 201039
Seville, 41001
About this study
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
The purpose of this study was to assess efficacy, safety, tolerability, and pharmacokinetics of ABBV-8E12 in participants with progressive supranuclear palsy (PSP).
Read the 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.
- Conditions
- Progressive Supranuclear Palsy
- Being tested
- Placebo, ABBV-8E12
- Keywords
- PSP, Steele-Richardson-Olszewski syndrome, Tauopathy
- Medical subject headings
- Supranuclear Palsy, Progressive, Tauopathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
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.
ABBV-8E12Drug
Also called Tilavonemab
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. For participants in Cohort 2, ABBV-8E12 doses may have been decreased after the evaluation by the Data Monitoring Committee of available safety, tolerability and pharmacokinetic data.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | 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 Receives: Drug: Placebo |
| ABBV-8E12 2000 mg | Experimental | 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) Receives: Drug: ABBV-8E12 |
| ABBV-8E12 4000 mg | Experimental | 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) Receives: Drug: ABBV-8E12 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline to Week 52 in Progressive Supranuclear Palsy Rating Scale (PSPRS) Total Score
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.
Measured: Baseline, Week 52
Number of Participants With Adverse Events
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.
Measured: 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 (17)
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 changes in score indicate worsening from baseline.
Measured: Baseline, Week 52
Clinical Global Impression of Change (CGI-C) Score at 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.
Measured: Week 52
Mean Change From Baseline to Week 52 in Midbrain Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI)
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.
Measured: 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) 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.
Measured: Baseline, Week 52
Maximum Observed Serum Concentration (Cmax) for ABBV-8E12
The maximum observed serum concentration after the first and the fifth doses in Cohort 1 and Cohort J1 was determined.
Measured: First Dosing Interval, 2 weeks, Day 1-14; Fifth Dosing Interval, 4 weeks, Day 85-113
Time to Maximum Observed Serum Concentration (Tmax) for ABBV-8E12
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.
Measured: First Dosing Interval, 2 weeks, Day 1-14; Fifth Dosing Interval, 4 weeks, Day 85-113
Area Under the Concentration Time Curve (AUC) for ABBV-8E12
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.
Measured: First Dosing Interval, 2 weeks, Day 1-14; Fifth Dosing Interval, 4 weeks, Day 85-113
Serum Concentration of ABBV-8E12 Prior to Infusion of a Day of Dosing (Ctrough)
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.
Measured: First day of the Fifth Dosing Interval, Day 85
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 changes in score indicate worsening from baseline.
Measured: Baseline, Week 52
Mean Change From Baseline to Week 52 in Progressive Supranuclear Palsy Health Related Quality of Life Scale (PSP-QoL) Total Score
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.
Measured: 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 changes in score indicate worsening from baseline.
Measured: Baseline, Week 52
Mean Change From Baseline to Week 52 in Third Ventricle Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI)
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.
Measured: Baseline, Week 52
Mean Change From Baseline to Week 52 in Superior Cerebellar Peduncle Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI)
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.
Measured: Baseline, Week 52
Mean Change From Baseline to Week 52 in Brainstem Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI)
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.
Measured: Baseline, Week 52
Mean Change From Baseline to Week 52 in Whole Brain Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI)
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.
Measured: Baseline, Week 52
Mean Change From Baseline to Week 52 in Frontal Lobe Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI)
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.
Measured: 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 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).
Measured: From Baseline to Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Dec 2016 (estimated)
- Study start12 Dec 2016
- Primary completion20 Nov 2019
- Study completion20 Nov 2019
Why it stopped: This study was prematurely discontinued because the program for progressive supranuclear palsy was discontinued due to lack of efficacy of study drug.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Progressive Supranuclear PalsyStudies of the same condition, open and under way.
- More trials run by AbbVieThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 378 participants (actual)
Sponsor and investigators
- Lead sponsor
- AbbVie
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- AbbVie Inc., Study director, AbbVie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02985879
- Sponsor's protocol ID
- M15-562
- Other IDs
- 2016-001635-12, 2016
- Status last verified
- Feb 2021
- First submitted
- 1 Dec 2016
- Last updated
- 3 Feb 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 33609476
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02985879
- Acronym / sponsor ID
- M15-562
- Conditions
- Progressive Supranuclear Palsy
- Keywords
- PSP, Steele-Richardson-Olszewski syndrome, Tauopathy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: This study was prematurely discontinued because the program for progressive supranuclear palsy was discontinued due to lack of efficacy of study drug.
- Enrolment
- 378 participants (actual)
- Lead sponsor
- AbbVieIndustry (pharma, biotech, devices)
- Study start
- 12 Dec 2016 (actual)
- Primary completion
- 20 Nov 2019 (actual)
- Study completion
- 20 Nov 2019 (actual)
- First posted
- 7 Dec 2016 (estimated)
- Results
- Posted 3 Feb 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo0.9% 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 | Experimental | Drug: ABBV-8E12Intravenous 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 | Experimental | Drug: ABBV-8E12Intravenous 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) |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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 (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboParticipants 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. | Drug | Placebo |
| ABBV-8E12Also: TilavonemabParticipants 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. For participants in Cohort 2, ABBV-8E12 doses may have been decreased after the evaluation by the Data Monitoring Committee of available safety, tolerability and pharmacokinetic data. | Drug | ABBV-8E12 2000 mg, ABBV-8E12 4000 mg |
Primary outcome
Change From Baseline to Week 52 in Progressive Supranuclear Palsy Rating Scale (PSPRS) Total Score
Time frame: 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
Time frame: 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.
17 secondary outcomes
Mean Change From Baseline to Week 52 in Unified Parkinson's Disease Rating Scale (UPDRS) Part II (Activities of Daily Living)
Time frame: Baseline, Week 52
Clinical Global Impression of Change (CGI-C) Score at Week 52
Time frame: Week 52
Mean Change From Baseline to Week 52 in Midbrain Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI)
Time frame: Baseline, Week 52
Mean Change From Baseline to Week 52 in Schwab and England Activities of Daily Living Scale (SEADL)
Time frame: Baseline, Week 52
Maximum Observed Serum Concentration (Cmax) for ABBV-8E12
Time frame: First Dosing Interval, 2 weeks, Day 1-14; Fifth Dosing Interval, 4 weeks, Day 85-113
Time to Maximum Observed Serum Concentration (Tmax) for ABBV-8E12
Time frame: First Dosing Interval, 2 weeks, Day 1-14; Fifth Dosing Interval, 4 weeks, Day 85-113
Area Under the Concentration Time Curve (AUC) for ABBV-8E12
Time frame: First Dosing Interval, 2 weeks, Day 1-14; Fifth Dosing Interval, 4 weeks, Day 85-113
Serum Concentration of ABBV-8E12 Prior to Infusion of a Day of Dosing (Ctrough)
Time frame: First day of the Fifth Dosing Interval, Day 85
Mean Change From Baseline to Week 52 in Clinical Global Impression of Severity (CGI-S) Score
Time frame: Baseline, Week 52
Mean Change From Baseline to Week 52 in Progressive Supranuclear Palsy Health Related Quality of Life Scale (PSP-QoL) Total Score
Time frame: Baseline, Week 52
Mean Change From Baseline to Week 52 in Progressive Supranuclear Palsy Staging System Score (PSP-SS) Score
Time frame: Baseline, Week 52
Mean Change From Baseline to Week 52 in Third Ventricle Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI)
Time frame: Baseline, Week 52
Mean Change From Baseline to Week 52 in Superior Cerebellar Peduncle Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI)
Time frame: Baseline, Week 52
Mean Change From Baseline to Week 52 in Brainstem Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI)
Time frame: Baseline, Week 52
Mean Change From Baseline to Week 52 in Whole Brain Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI)
Time frame: Baseline, Week 52
Mean Change From Baseline to Week 52 in Frontal Lobe Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI)
Time frame: Baseline, Week 52
Time to Loss of Ability to Walk Independently as Measured by Progressive Supranuclear Palsy Rating Scale (PSPRS) Item 26
Time frame: From Baseline to Week 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33609476Hoglinger 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.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
AbbVie Inc. study director
AbbVie
66 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ABBV-8E12 in people with Progressive Supranuclear Palsy, run by AbbVie at 66 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 3 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 66 sites in United States, Japan, Italy, France, Australia and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Feb 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline to Week 52 in Progressive Supranuclear Palsy Rating Scale (PSPRS) Total Score (time frame: Baseline, Week 52). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02985879, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Feb 2021.