A Study to Assess Efficacy, Safety, Tolerability, and Pharmacokinetics of ABBV-8E12 in Subjects With Progressive Supranuclear Palsy (PSP)

NCT02985879 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: M15-5622016-001635-12
• Study Type: interventional
• Target: 378
• Locations: 8 countries
• Sites: 66

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).

Conditions

Progressive Supranuclear Palsy

Keywords

PSP; Steele-Richardson-Olszewski syndrome; Tauopathy

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  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)

  Baseline, Week 52

• Clinical Global Impression of Change (CGI-C) Score at Week 52

  Week 52

• Mean Change From Baseline to Week 52 in Midbrain Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI)

  Baseline, Week 52

• Mean Change From Baseline to Week 52 in Schwab and England Activities of Daily Living Scale (SEADL)

  Baseline, Week 52

• Maximum Observed Serum Concentration (Cmax) for ABBV-8E12

  First Dosing Interval, 2 weeks, Day 1-14; Fifth Dosing Interval, 4 weeks, Day 85-113

Study Arms (3)

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

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)

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)

Drug: ABBV-8E12

Interventions

Placebo DRUG

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.

Placebo

ABBV-8E12 DRUG

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.

Also known as: Tilavonemab

ABBV-8E12 2000 mg; ABBV-8E12 4000 mg

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• AbbVie: lead

Study Sites (66)

University of Alabama at Birmingham - Main /ID# 144892

Birmingham, Alabama, 35233, United States

Location

Mayo Clinic - Scottsdale /ID# 144893

Scottsdale, Arizona, 85259, United States

Location

Cedars-Sinai Medical Center /ID# 149775

Beverly Hills, California, 90211, United States

Location

Ucsd /Id# 144905

La Jolla, California, 92093, United States

Location

Usc /Id# 149773

Los Angeles, California, 90033, United States

Location

University of California, Los Angeles /ID# 144896

Los Angeles, California, 90095, United States

Location

Univ California, San Francisco /ID# 144897

San Francisco, California, 94143-2204, United States

Location

Rocky Mountain Movement Disorders Center /ID# 153397

Englewood, Colorado, 80113-2736, United States

Location

University of Florida - Archer /ID# 144906

Gainesville, Florida, 32610, United States

Location

Mayo Clinic /ID# 144911

Jacksonville, Florida, 32224, United States

Location

University of South Florida /ID# 144912

Tampa, Florida, 33612, United States

Location

Georgia Regents University /ID# 144908

Augusta, Georgia, 30912, United States

Location

Rush University Medical Center /ID# 144894

Chicago, Illinois, 60612, United States

Location

University of Chicago /ID# 148672

Chicago, Illinois, 60637-1443, United States

Location

Indiana University /ID# 149036

Indianapolis, Indiana, 46202, United States

Location

University of Kentucky Chandler Medical Center /ID# 144891

Lexington, Kentucky, 40536, United States

Location

Mayo Clinic - Rochester /ID# 144895

Rochester, Minnesota, 55905-0001, United States

Location

St. Luke's Hosp. of Kansas Cit /ID# 168629

Kansas City, Missouri, 64111, United States

Location

Cleveland Clinic Lou Ruvo Cent /ID# 148919

Las Vegas, Nevada, 89106, United States

Location

Rutgers Robert Wood Johnson /ID# 144901

New Brunswick, New Jersey, 08901, United States

Location

COLUMBIA University Medical Center /ID# 149037

New York, New York, 10032-3725, United States

Location

Cleveland Clinic Main Campus /ID# 144885

Cleveland, Ohio, 44195, United States

Location

Oregon Health and Science University /ID# 149774

Portland, Oregon, 97239, United States

Location

Vanderbilt Univ Med Ctr /ID# 144898

Nashville, Tennessee, 37232-0011, United States

Location

Kerwin Research Center /ID# 144904

Dallas, Texas, 75231-4316, United States

Location

McGovern Medical School /ID# 149236

Houston, Texas, 77054, United States

Location

Central Texas Neurology Consul /ID# 167417

Round Rock, Texas, 78681, United States

Location

Westmead Hospital /ID# 154403

Westmead, New South Wales, 2145, Australia

Location

Q-Pharm Pty Limited /ID# 154410

Herston, Queensland, 4006, Australia

Location

Royal Adelaide Hospital /ID# 153157

Adelaide, South Australia, 5000, Australia

Location

Alfred Hospital /ID# 153158

Melbourne, Victoria, 3004, Australia

Location

Neurodegenerative Disorders Re /ID# 153770

West Perth, Western Australia, 6005, Australia

Location

University of Calgary /ID# 154393

Calgary, Alberta, T2N 4Z6, Canada

Location

OCT Research ULC /ID# 169688

Kelowna, British Columbia, V1Y 1Z9, Canada

Location

Toronto Western Hospital /ID# 152818

Toronto, Ontario, M5T 2S8, Canada

Location

Crchum /Id# 152819

Montreal, Quebec, H2X 0A9, Canada

Location

Montreal Neurological Institut /ID# 156413

Montreal, Quebec, H3A 2B4, Canada

Location

Hopital Universitaire Purpan /ID# 153152

Toulouse, Haute-Garonne, 31059, France

Location

Hopital de la Timone /ID# 153113

Marseille, Provence-Alpes-Côte d'Azur Region, 13385, France

Location

Chu de Bordeaux Hopital /Id# 153151

Bordeaux, 33076, France

Location

Hopital B Roger Salengro /ID# 153943

Lille, 59037, France

Location

Hopital Pitie Salpetriere /ID# 153942

Paris, 75651, France

Location

CHU Strasbourg Hautepierre Hos /ID# 206942

Strasbourg, 67200, France

Location

St. Josef-Hospital /ID# 201984

Bochum, North Rhine-Westphalia, 44791, Germany

Location

Universitaetsklinikum Leipzig /ID# 201761

Leipzig, Saxony, 04103, Germany

Location

Universitaetsklinikum Ulm /ID# 153155

Ulm, Thuringia, 89081, Germany

Location

KH Agatharied /ID# 154166

Hausham, 83734, Germany

Location

TU Uniklinik Munchen /ID# 153154

Munich, 80802, Germany

Location

Universita di Catanzaro Magna Graecia /ID# 166322

Catanzaro, Calabria, 88100, Italy

Location

Policlinico Agostino Gemelli /ID# 153104

Rome, Lazio, 00168, Italy

Location

IBD Center - IRCCS Istituto Clinico Humanitas /ID# 155092

Rozzano, Milano, 20089, Italy

Location

Fondazione IRCCS Istituto Neurologico Carlo Besta /ID# 201982

Milan, 20133, Italy

Location

Istituto Neuro Mediterraneo IR /ID# 153106

Pozzilli, 86077, Italy

Location

A.O. Santa Maria /ID# 153102

Terni, 05100, Italy

Location

IRCCS Ospedale San Camillo /ID# 153101

Venezia LIDO, 30126, Italy

Location

National Hospital Organization Higashinagoya National Hospital /ID# 201514

Nagoya, Aichi-ken, 4658620, Japan

Location

National Hospital Organization Asahikawa Medical Center /ID# 201585

Asahikawa, Hokkaido, 070-8644, Japan

Location

National Hospital Organization Utano National Hospital /ID# 201979

Kyoto, Kyoto, 616-8255, Japan

Location

Tohoku University Hospital /ID# 202307

Sendai, Miyagi, 980-8574, Japan

Location

NHO Sendai Nishitaga National Hospital /ID# 202132

Sendai, Miyagi, 982-8555, Japan

Location

Niigata University Medical & Dental Hospital /ID# 201680

Niigata, Niigata, 951-8520, Japan

Location

Osaka University Hospital /ID# 201980

Suita-shi, Osaka, 565-0871, Japan

Location

Juntendo University Hospital /ID# 200870

Bunkyo-ku, Tokyo, 113-8431, Japan

Location

National Center of Neurology and Psychiatry /ID# 202037

Kodaira, Tokyo, 187-8551, Japan

Location

Hospital General Universitario Gregorio Maranon /ID# 200876

Madrid, 28007, Spain

Location

Hosp Univ Virgen del Rocio /ID# 201039

Seville, 41001, Spain

Location

Related Publications (1)

• 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.

  PMID: 33609476 DERIVED

MeSH Terms

Conditions

Supranuclear Palsy, Progressive; Tauopathies

Interventions

tilavonemab

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Ophthalmoplegia; Ocular Motility Disorders; Cranial Nerve Diseases; Neurodegenerative Diseases; Paralysis; Neurologic Manifestations; Eye Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie

abbvieclinicaltrials@abbvie.com

800-633-9110

Study Officials

• AbbVie Inc.

  AbbVie

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2016
• First Posted: December 7, 2016
• Study Start: December 12, 2016
• Primary Completion: November 20, 2019
• Study Completion: November 20, 2019
• Last Updated: February 3, 2021
• Results First Posted: February 3, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
• 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.

Locations

JP (9); FR (6); DE (5); IT (7); US (27); ES (2); AU (5); CA (5)