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

NCT ID: NCT02985879

Last Updated: 2021-02-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 378 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-12
• Study Completion Date: 2019-11-20

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.

Conditions

Progressive Supranuclear Palsy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: 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.

ABBV-8E12 2000 mg

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)

Group Type: EXPERIMENTAL

ABBV-8E12

Intervention Type: 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.

ABBV-8E12 4000 mg

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)

Group Type: EXPERIMENTAL

ABBV-8E12

Intervention Type: 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.

Interventions

Placebo

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.

Intervention Type: 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. 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.

Intervention Type: DRUG

Other Intervention Names

Tilavonemab

Eligibility Criteria

Inclusion Criteria

• 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)

Exclusion Criteria

• 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

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

AbbVie Inc.

Role: STUDY_DIRECTOR

AbbVie

Locations

University of Alabama at Birmingham - Main /ID# 144892

Birmingham, Alabama, United States

Mayo Clinic - Scottsdale /ID# 144893

Scottsdale, Arizona, United States

Cedars-Sinai Medical Center /ID# 149775

Beverly Hills, California, United States

Ucsd /Id# 144905

La Jolla, California, United States

Usc /Id# 149773

Los Angeles, California, United States

University of California, Los Angeles /ID# 144896

Los Angeles, California, United States

Univ California, San Francisco /ID# 144897

San Francisco, California, United States

Rocky Mountain Movement Disorders Center /ID# 153397

Englewood, Colorado, United States

University of Florida - Archer /ID# 144906

Gainesville, Florida, United States

Mayo Clinic /ID# 144911

Jacksonville, Florida, United States

University of South Florida /ID# 144912

Tampa, Florida, United States

Georgia Regents University /ID# 144908

Augusta, Georgia, United States

Rush University Medical Center /ID# 144894

Chicago, Illinois, United States

University of Chicago /ID# 148672

Chicago, Illinois, United States

Indiana University /ID# 149036

Indianapolis, Indiana, United States

University of Kentucky Chandler Medical Center /ID# 144891

Lexington, Kentucky, United States

Mayo Clinic - Rochester /ID# 144895

Rochester, Minnesota, United States

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

Kansas City, Missouri, United States

Cleveland Clinic Lou Ruvo Cent /ID# 148919

Las Vegas, Nevada, United States

Rutgers Robert Wood Johnson /ID# 144901

New Brunswick, New Jersey, United States

COLUMBIA University Medical Center /ID# 149037

New York, New York, United States

Cleveland Clinic Main Campus /ID# 144885

Cleveland, Ohio, United States

Oregon Health and Science University /ID# 149774

Portland, Oregon, United States

Vanderbilt Univ Med Ctr /ID# 144898

Nashville, Tennessee, United States

Kerwin Research Center /ID# 144904

Dallas, Texas, United States

McGovern Medical School /ID# 149236

Houston, Texas, United States

Central Texas Neurology Consul /ID# 167417

Round Rock, Texas, United States

Westmead Hospital /ID# 154403

Westmead, New South Wales, Australia

Q-Pharm Pty Limited /ID# 154410

Herston, Queensland, Australia

Royal Adelaide Hospital /ID# 153157

Adelaide, South Australia, Australia

Alfred Hospital /ID# 153158

Melbourne, Victoria, Australia

Neurodegenerative Disorders Re /ID# 153770

West Perth, Western Australia, Australia

University of Calgary /ID# 154393

Calgary, Alberta, Canada

OCT Research ULC /ID# 169688

Kelowna, British Columbia, Canada

Toronto Western Hospital /ID# 152818

Toronto, Ontario, Canada

Crchum /Id# 152819

Montreal, Quebec, Canada

Montreal Neurological Institut /ID# 156413

Montreal, Quebec, Canada

Hopital Universitaire Purpan /ID# 153152

Toulouse, Haute-Garonne, France

Hopital de la Timone /ID# 153113

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

Chu de Bordeaux Hopital /Id# 153151

Bordeaux, , France

Hopital B Roger Salengro /ID# 153943

Lille, , France

Hopital Pitie Salpetriere /ID# 153942

Paris, , France

CHU Strasbourg Hautepierre Hos /ID# 206942

Strasbourg, , France

St. Josef-Hospital /ID# 201984

Bochum, North Rhine-Westphalia, Germany

Universitaetsklinikum Leipzig /ID# 201761

Leipzig, Saxony, Germany

Universitaetsklinikum Ulm /ID# 153155

Ulm, Thuringia, Germany

KH Agatharied /ID# 154166

Hausham, , Germany

TU Uniklinik Munchen /ID# 153154

Munich, , Germany

Universita di Catanzaro Magna Graecia /ID# 166322

Catanzaro, Calabria, Italy

Policlinico Agostino Gemelli /ID# 153104

Rome, Lazio, Italy

IBD Center - IRCCS Istituto Clinico Humanitas /ID# 155092

Rozzano, Milano, Italy

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, Aichi-ken, Japan

National Hospital Organization Asahikawa Medical Center /ID# 201585

Asahikawa, Hokkaido, Japan

National Hospital Organization Utano National Hospital /ID# 201979

Kyoto, Kyoto, Japan

Tohoku University Hospital /ID# 202307

Sendai, Miyagi, Japan

NHO Sendai Nishitaga National Hospital /ID# 202132

Sendai, Miyagi, Japan

Niigata University Medical & Dental Hospital /ID# 201680

Niigata, Niigata, Japan

Osaka University Hospital /ID# 201980

Suita-shi, Osaka, Japan

Juntendo University Hospital /ID# 200870

Bunkyo-ku, Tokyo, Japan

National Center of Neurology and Psychiatry /ID# 202037

Kodaira, Tokyo, Japan

Hospital General Universitario Gregorio Maranon /ID# 200876

Madrid, , Spain

Hosp Univ Virgen del Rocio /ID# 201039

Seville, , Spain

Countries

United States; Australia; Canada; France; Germany; Italy; Japan; Spain

References

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.

Reference Type: DERIVED

PMID: 33609476 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-001635-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

M15-562

Identifier Type: -

Identifier Source: org_study_id