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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02985879
Recruitment Status : Terminated (This study was prematurely discontinued because the program for progressive supranuclear palsy was discontinued due to lack of efficacy of study drug.)
First Posted : December 7, 2016
Results First Posted : February 3, 2021
Last Update Posted : February 3, 2021
Sponsor:
Information provided by (Responsible Party):
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).

Condition or disease Intervention/treatment Phase
Progressive Supranuclear Palsy Drug: Placebo Drug: ABBV-8E12 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 378 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : December 12, 2016
Actual Primary Completion Date : November 20, 2019
Actual Study Completion Date : November 20, 2019


Arm Intervention/treatment
Placebo Comparator: 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
Drug: 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.

Experimental: 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)
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.
Other Name: Tilavonemab

Experimental: 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)
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.
Other Name: Tilavonemab




Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. 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 ]
    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.

  2. Clinical Global Impression of Change (CGI-C) Score at Week 52 [ Time Frame: 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.

  3. Mean Change From Baseline to Week 52 in Midbrain Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI) [ Time Frame: 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.

  4. Mean Change From Baseline to Week 52 in Schwab and England Activities of Daily Living Scale (SEADL) [ Time Frame: 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.

  5. 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 ]
    The maximum observed serum concentration after the first and the fifth doses in Cohort 1 and Cohort J1 was determined.

  6. 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 ]
    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.

  7. 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 ]
    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.

  8. 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 ]
    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.

  9. Mean Change From Baseline to Week 52 in Clinical Global Impression of Severity (CGI-S) Score [ Time Frame: 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.

  10. 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 ]
    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.

  11. Mean Change From Baseline to Week 52 in Progressive Supranuclear Palsy Staging System Score (PSP-SS) Score [ Time Frame: 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.

  12. Mean Change From Baseline to Week 52 in Third Ventricle Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI) [ Time Frame: 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.

  13. 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 ]
    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.

  14. Mean Change From Baseline to Week 52 in Brainstem Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI) [ Time Frame: 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.

  15. Mean Change From Baseline to Week 52 in Whole Brain Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI) [ Time Frame: 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.

  16. Mean Change From Baseline to Week 52 in Frontal Lobe Atrophy As Measured by Volumetric Magnetic Resonance Imaging (MRI) [ Time Frame: 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.

  17. 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 ]
    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).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key 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)

Key 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02985879


Locations
Show Show 66 study locations
Sponsors and Collaborators
AbbVie
Investigators
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Study Director: AbbVie Inc. AbbVie
  Study Documents (Full-Text)

Documents provided by AbbVie:
Study Protocol  [PDF] December 13, 2018
Statistical Analysis Plan  [PDF] October 23, 2018

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT02985879    
Other Study ID Numbers: M15-562
2016-001635-12 ( EudraCT Number )
First Posted: December 7, 2016    Key Record Dates
Results First Posted: February 3, 2021
Last Update Posted: February 3, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (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.
URL: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html

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Studies a U.S. FDA-regulated Drug Product: Yes
Product Manufactured in and Exported from the U.S.: No
Keywords provided by AbbVie:
PSP
Steele-Richardson-Olszewski syndrome
Tauopathy
Additional relevant MeSH terms:
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Supranuclear Palsy, Progressive
Paralysis
Neurologic Manifestations
Nervous System Diseases
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Movement Disorders
Ophthalmoplegia
Ocular Motility Disorders
Cranial Nerve Diseases
Tauopathies
Neurodegenerative Diseases
Eye Diseases
Tilavonemab
Nootropic Agents