An Extension Study of ABBV-8E12 in Progressive Supranuclear Palsy (PSP)

Study Overview
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Brief Summary
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The purpose of this study was to assess the long-term safety and efficacy of ABBV-8E12 (tilavonemab) in participants with progressive supranuclear palsy (PSP).

Detailed Description
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This study (M15-563) was a Phase 2, randomized, double-blind, multiple-dose, multicenter, long-term extension of NCT 02985879 (Study M15-562) in participants with progressive supranuclear palsy (PSP). Those who completed the 52-week Treatment Period in Study M15-562 and met all entry criteria were eligible for enrollment into this study. This study planned for a Treatment Period of up to 5 years and a post-treatment follow-up visit approximately 20 weeks after the last dose of study drug (including participants who prematurely discontinued treatment). All participants received ABBV-8E12 as follows: those who received placebo in Study M15-562 were randomized, in a 1:1 ratio, to either 2000 or 4000 mg; those who received ABBV-8E12 at a dose of either 2000 or 4000 mg in Study M15-562 continued on the same dose in this study. This study was prematurely discontinued because the program for progressive supranuclear palsy was discontinued due to lack of efficacy.

Official Title
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An Extension Study of ABBV-8E12 in Progressive Supranuclear Palsy (PSP)

Conditions
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Progressive Supranuclear Palsy (PSP)

Intervention / Treatment
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* Drug: ABBV-8E12
* Drug: Placebo solution for IV infusion on Day 15


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant completed the 52-week treatment period in Study M15-562 (NCT02985879) In the opinion of the investigator, the participant was compliant during participation in Study M15-562 (NCT02985879) 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 the time of study entry Any contraindication or inability to tolerate brain magnetic resonance imaging (MRI) Participant has any significant change in his/her medical condition that could interfere with the subject's participation in the study, could place the subject at increased risk, or could confound interpretation of study results More than 8 weeks have elapsed since the participant received his/her last dose of study drug in Study M15-562 (NCT02985879) Participant is considered by the investigator, for any reason, to be an unsuitable candidate to receive ABBV-8E12 or the participant is considered by the investigator to be unable or unlikely to comply with the dosing schedule or study evaluations

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: M15-562 ABBV-8E12 2000 mg/M15-563 ABBV-8E12 2000 mg<br>Intravenous (IV) infusions of 2000 mg ABBV-8E12 at Day 1 and Day 29, then every 28 days for up to 5 years; administered at 300 mg/15 mL and 1000 mg/10 mL strength. Placebo IV infusion was administered on Day 15 in Study M15-563 (to maintain the blind in Study M15-562). | Drug: ABBV-8E12<br>* 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.<br>* Other names: Tilavonemab;Drug: Placebo solution for IV infusion on Day 15<br>* 0.9% NaCl injection/solution for infusion 500 mL; 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.<br>|
| Experimental: M15-562 ABBV-8E12 4000 mg/M15-563 ABBV-8E12 4000 mg<br>Intravenous (IV) infusions of 4000 mg ABBV-8E12 at Day 1 and Day 29, then every 28 days for up to 5 years; administered at 300 mg/15 mL and 1000 mg/10 mL strength. Placebo IV infusion was administered on Day 15 in Study M15-563 (to maintain the blind in Study M15-562). | Drug: ABBV-8E12<br>* 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.<br>* Other names: Tilavonemab;Drug: Placebo solution for IV infusion on Day 15<br>* 0.9% NaCl injection/solution for infusion 500 mL; 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.<br>|
| Experimental: M15-562 Placebo/M15-563 ABBV-8E12 2000 mg<br>Intravenous (IV) infusions of 2000 mg ABBV-8E12 at Day 1, Day 15, and Day 29, then every 28 days for up to 5 years; administered at 300 mg/15 mL and 1000 mg/10 mL strength. | Drug: ABBV-8E12<br>* 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.<br>* Other names: Tilavonemab;|
| Experimental: M15-562 Placebo/M15-563 ABBV-8E12 4000 mg<br>Intravenous (IV) infusions of 4000 mg ABBV-8E12 at Day 1, Day 15, and Day 29, then every 28 days for up to 5 years; administered at 300 mg/15 mL and 1000 mg/10 mL strength. | Drug: ABBV-8E12<br>* 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.<br>* Other names: Tilavonemab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Progressive Supranuclear Palsy Rating Scale (PSPRS) Total Score 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. Positive values indicate worsening from baseline. | Baseline, Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 values indicate worsening from baseline. | Baseline, Week 52 | 
| Change in Clinical Global Impression of Severity (CGI-C) Score From Baseline to 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. | 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) scale 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 values indicate worsening from baseline. | Baseline, Week 52 | 
| 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 values indicate worsening from baseline. | Baseline, Week 52 | 
| Patient Global Impression of Change Score (PGI-C) Score From Baseline to Week 52 | The PGI-C is a participant's rating of the change in their PSP-related symptoms since initiation of study drug. Participants rated their change in status using the following 7-point scale: 1 = Very much improved; 2 = Much improved; 3 = Minimally improved; 4 = No change; 5 = Minimally worse; 6 = Much worse; 7 = Very much worse. | 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 values indicate worsening from baseline. | 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 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. 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). | From Baseline to Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PSP, Tauopathy, Steele-Richardson-Olszewski Syndrome