A Study to Investigate Arbaclofen ER Tablets for the Treatment of Spasticity in Patients With Multiple Sclerosis

A Randomized, Double-Blind, Placebo-Controlled Parallel Group Study to Investigate the Safety and Efficacy of Arbaclofen Extended-Release Tablets for the Treatment of Spasticity in Patients With Multiple Sclerosis (Study OS440-3006)

This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the safety and efficacy of oral arbaclofen ER tablets in MS patients with spasticity. Arbaclofen ER will be compared with placebo.

Study Overview

• Status: Not yet recruiting
• Conditions: Spasticity
• Intervention / Treatment: Drug: Placebo; Drug: Arbaclofen

Detailed Description

This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the safety and efficacy of oral arbaclofen ER tablets (80 mg/day) in MS patients with spasticity. Arbaclofen ER will be compared with placebo. The treatment groups will be randomized in a 1:1 ratio. There will be a 49-day dose escalation period, followed by a 84-day maintenance treatment period, followed by a 21-day taper period.

• Study Type: Interventional
• Enrollment (Estimated): 442
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Joann Stavole; Phone Number: 9088091343; Email: jstavole@rvlpharma.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subjects 18 to 65 years of age, inclusive
• An established diagnosis per McDonald Criteria (Polman et al 2011) of MS (either RR or SP course) that manifests a documented history of spasticity for at least 6 months prior to screening
• Spasticity due to MS as shown by a TNmAS-MAL score ≥ 2
• Expanded Disability Status Scale (EDSS) score greater than or equal to (≥) 3.0 and less than or equal to (≤) 7.0
• Absence of infections, peripheral vascular disease, painful contractures, advanced arthritis, or other conditions that hinder evaluation of joint movement
• Use of a medically highly effective form of birth control (see Section 7.8) during the study and for 3 months thereafter for women of child-bearing potential (including female subjects and female partners of non-sterile male subjects)
• Willing to sign the informed consent form (ICF)

Exclusion Criteria:

• Any concomitant disease or disorder that has symptoms of spasticity or that may influence the subject's level of spasticity
• In the opinion of the investigator, the patient is unable to rate their level of spasticity or distinguish it from other MS symptoms
• Concomitant use of medications that would potentially interfere with the actions of the study medication or outcome variables
• Pregnancy, lactation, or planned pregnancy during the course of the study and for 3 months after the final study visit
• Current significant cognitive deficit, severe or untreated anxiety, severe or untreated depression
• Current malignancy or history of malignancy that has not been in remission for more than 5 years, except effectively treated basal cell skin carcinoma
• Any other significant disease, disorder, or significant laboratory finding which, in the opinion of the investigator, puts the subject at risk because of participation, influences the result of the study, or affects the subject's ability to participate

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arbaclofen Extended-Release; Extended-release oral tablet, twice daily dosing (80 mg/day)	Drug: Arbaclofen; Arbaclofen Extended Release Tablets; Other Names: AERT; OS440
Placebo Comparator: Placebo; Extended-release oral tablet, twice daily dosing	Drug: Placebo; Placebo tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline to Maintenance Treatment Period for Total Numeric-Transformed Modified Ashworth Scale Most Affected Limb (TNmAS-MAL)	The total numerical score of a limb accounts for the sum of the 3 main joint muscular group scores. The limb with the highest score is the most affected limb. Lower score is better. Scale is from 0 to 5.	Maintenance Treatment Period: Visit 5 (day 77), Visit 6 (day 105), and Visit 7 (day 133)
Responder Analysis of Ashworth Scale Score (AS-MAL-R) for Maintenance Treatment Period	Responder status (AS-MAL-R) consists of three response categorical outcomes based on the Ashworth Scale (AS). Where the possible outcomes are: Strong Responder, Responder, or Non-Responder	Maintenance Treatment Period: Visit 5 (day 77), Visit 6 (day 105), and Visit 7 (day 133)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline to Maintenance Treatment Period for Total Numeric-Transformed Modified Ashworth Scale Total Limbs (TNmAS-TL)	The total numerical score of a limb accounts for the sum of the 3 main joint muscular group scores. The total of the 4 limbs is the total limbs score. Lower score is better. Scale is from 0 to 5 per joint, Maximum score per limb is 15. Maximum total limbs score is 60.	Maintenance Treatment Period: Visit 5 (day 77), Visit 6 (day 105), and Visit 7 (day 133)
Clinician's global impression of change (CGIC) for Maintenance Treatment Period	The clinician makes a judgment about the change from baseline of illness severity, the subject's level of distress, other aspects of impairment, and the impact of the illness on functioning. Scale of -3 to +3, higher score is better	Maintenance Treatment Period: Visit 5 (day 77), Visit 6 (day 105), and Visit 7 (day 133)
Numeric Rating Scale of Spasticity (NRS-S) for Maintenance Treatment Period	The Numeric Rating Scale of Spasticity is a patient rated measure of the perceived severity of spasticity using a 0-10 numeric rating scale. Lower score is better.	Maintenance Treatment Period: Visit 5 (day 77), Visit 6 (day 105), and Visit 7 (day 133)
Expanded Disability Status Scale (EDSS) for Maintenance Treatment Period	EDSS is a method of quantifying disability in MS and monitoring changes in the level of disability over time. Scale ranges from 0-10, in 0.5 unit increments. Lower score is better.	Maintenance Treatment Period: Visit 5 (day 77), Visit 6 (day 105), and Visit 7 (day 133)

Collaborators and Investigators

• Sponsor: RVL Pharmaceuticals, Inc.
• Investigators: Study Director: Tina deVries, PhD, RVL Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: November 12, 2021
• First Submitted That Met QC Criteria: December 16, 2021
• First Posted (Actual): January 5, 2022

Study Record Updates

• Last Update Posted (Estimated): December 3, 2025
• Last Update Submitted That Met QC Criteria: November 25, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Muscle Spasticity; arbaclofen placarbil
• Other Study ID Numbers: OS440-3006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No