Multiple SclerosisPhase 3OS440-3004NCT03290131
A Study to Investigate the Safety and Effectiveness of Arbaclofen Extended-Release Tablets for Patients With MS
A Phase 3 study testing Arbaclofen in people with Multiple Sclerosis and Spasticity, Muscle, run by RVL Pharmaceuticals, Inc. at 30 sites in 7 countries.
Trial summary
Multiple Sclerosis (MS) is an acquired inflammatory demyelinating disease of the central nervous system (CNS) that is regarded as the foremost cause of non-traumatic neurologic disability in adults in North America. Spasticity is a common complication in MS and occurs in up to 84% of patients. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Multiple Sclerosis, Spasticity, Muscle
- What is being tested?
- Arbaclofen
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 536 participants
- Where
- 30 sitesin 7 countries
- Study dates
- 28 Jan 2018to 2 Jan 2019
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects 18 to 65 years of age, inclusive.
- An established diagnosis of MS that manifests a documented history of spasticity.
- If receiving disease-modifying medications (eg, interferons approved for MS, glatiramer acetate, natalizumab, fingolimod, or mitoxantrone), there must be no change in dose for at least 3 months prior to Visit 1 (Screening), and the subject must be willing to maintain this treatment dose for the duration of the study. If receiving AMPYRA® (dalfampridine, fampridine, 4-amino puridine), subject must be at a stable dose for at least 3 months prior to Visit 1.
- Stable regimen for at least 3 months prior to Visit 2 for all medications and non-pharmacological therapies that are intended to alleviate spasticity.
- 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).
Who cannot join
- Any concomitant disease or disorder that has symptoms of spasticity or that may influence the subject's level of spasticity.
- 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.
- Subject has clinically significant abnormal laboratory values, in the opinion of the investigator, at Visit 1 or Visit 2.
- 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.
Trial locations and contacts
30 sites in 7 countries.
30 sites in 7 countries
Poland7 sites
Dendryt Medical Center
Katowice
Neuro-Medic
Katowice
Neurology Center Krzysztof Selmaj
Lodz
Medical Practice Professor K. Rejdak
Lublin
MED-Polonia, Sp. z o.o. (LLC)
Poznan
"MEDYK" Stanislaw Mazur Sp. z o.o. (LLC) Medical Centre
Rzeszów
NeuroProtect Medical Center
Warsaw
Bulgaria6 sites
Multiprofile Hospital for Active Treatment - Pleven within the structure of Military Medical Academy, Sofia
Pleven
University Multiprofile Hospital for Active Treatment "Dr. Georgi Stranski", Pleven, Clinic of Neurological Diseases
Pleven
Medical Center "Rusemed" EOOD
Rousse
Multiprofile Hospital for Active Treatment "ACIBADEM City Clinic Tokuda Hospital", Sofia, Neurology and Sleep Medicine Clinic
Sofia
Multiprofile Hospital for Active Treatment of Neurology and Psychiatry "Sveti Naum", Sofia
Sofia
University Multiprofile Hospital for Active Treatment "Sveti Ivan Rilski", Sofia, Clinic of Neurology Diseases
Sofia
Belarus5 sites
Grodno Regional Clinical Hospital
Grodno
Minsk City Clinical Hospital #5
Minsk
Minsk Scientific and Practical Center of Surgery, Transplantology and Hematology
Minsk
Republican Research and Development Center for Neurology and Neurosurgery
Minsk
Vitebsk Regional Diagnostic Center
Vitebsk
Croatia4 sites
Clinical Hospital Center Osijek, Clinic of Neurology
Osijek
Clinical Hospital Center Rijeka, Department of Neurology
Rijeka
General Hospital Varazdin, Department of Neurology
Varaždin
Clinical Hospital Dubrava, Department of Neurology
Zagreb
Serbia4 sites
Clinical Center of Serbia
Belgrade
Clinical Hospital Center Zemun, Department of Neurology
Belgrade
Clinical Hospital Center Zvezdara
Belgrade
Clinical Center Kragujevac
Kragujevac
Bosnia and Herzegovina2 sites
University Clinical Centre of the Republic of Srpska, Clinic of Neurology
Banja Luka
University Clinical Hospital Mostar, Clinic of Neurology
Mostar
Moldova2 sites
Institute for Emergency Medicine
Chisinau
National Institute of Neurology and Neurosurgery
Chisinau
About this study
Official title: 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
Multiple Sclerosis (MS) is an acquired inflammatory demyelinating disease of the central nervous system (CNS) that is regarded as the foremost cause of non-traumatic neurologic disability in adults in North America. Spasticity is a common complication in MS and occurs in up to 84% of patients. The main sign of spasticity is resistance to passive limb movement characterized by increased resistance to stretching, clonus, and exaggerated deep reflexes. Osmotica Pharmaceutical is currently developing arbaclofen extended-release tablets (AERT) for the treatment of spasticity in patients with MS.
Read the detailed description
This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the safety and efficacy of oral AERT in MS patients with spasticity. Two doses of AERT, 40 mg and 80 mg, will be compared with placebo. The treatment groups will be randomized in a 1:1:1 ratio. Eligible patients will undergo a washout period for withdrawal of all medications used for anti-spasticity and/or muscle relaxation prior to randomization. A baseline clinical evaluation will be performed (Visit 2) to confirm eligibility for study randomization, and subjects will be randomly assigned to 1 of 3 treatment arms. Subjects will remain on maintenance treatment for approximately 3 months.
- Conditions
- Multiple Sclerosis, Spasticity, Muscle
- Being tested
- Arbaclofen, Placebo
- Medical subject headings
- Multiple Sclerosis, Muscle Spasticity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ArbaclofenDrug
Also called AERT
Arbaclofen Extended Release Tablet
PlaceboDrug
Placebo comparator
| Study group | Role | What they receive |
|---|---|---|
| AERT 40 mg | Active comparator | 40 mg Arbaclofen Extended-Release Tablets Receives: Drug: Arbaclofen |
| AERT 80 mg | Active comparator | 80 mg Arbaclofen Extended-Release Tablets Receives: Drug: Arbaclofen |
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Total Numeric-transformed Modified Ashworth Scale Score of the Most Affected Limb (TNmAS-MAL)
Total Numeric-Transformed Modified Ashworth Scale (TNmAS) is a 6-point scale to measure abnormality in tone or the resistance to passive movements. Higher score is worse outcome.
For each joint, the minimum score is 0; maximum score is 5. The values for each of the 3 main joints are summed for the limb score. The limb with the highest score is the most affected limb (MAL). The highest possible score for a limb is 15. Limb range: 0 to 15.
To arrive at total limbs (TL) score the values for all 4 limbs are summed; maximum total limb score is 60. TL range: 0 to 60.
Measured: 84 days
Clinical Global Impression of Change (CGIC)
The Clinical Global Impression of Change (CGIC) was developed to provide a brief, stand-alone assessment of the clinician's view of the subject's global functioning prior to and after initiating a study medication. The scale ranges from -3 to +3 judging whether the change is significantly worse (-3) to significantly improved (+3). Higher score is better outcome. The CGIC scale will be used to measure the overall change in the subject's condition since starting the study. There is no baseline value because the score is a measure of how the patient changed from baseline (treatment initiation).
Measured: 84 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2017
- Study start28 Jan 2018
- Primary completion3 Dec 2018
- Study completion2 Jan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 536 participants (actual)
Sponsor and investigators
- Lead sponsor
- RVL Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Osmotica Pharmaceutical US LLC
- Responsible party
- Sponsor
- Investigators
- David Jacobs, MD, Study director, Vice President
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03290131
- Sponsor's protocol ID
- OS440-3004
- Acronym
- OS440-3004
- Status last verified
- May 2022
- First submitted
- 19 Sep 2017
- Last updated
- 15 Jul 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03290131
- Acronym / sponsor ID
- OS440-3004 / OS440-3004
- Conditions
- Multiple Sclerosis, Spasticity, Muscle
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 536 participants (actual)
- Lead sponsor
- RVL Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Osmotica Pharmaceutical US LLC
- Study start
- 28 Jan 2018 (actual)
- Primary completion
- 3 Dec 2018 (actual)
- Study completion
- 2 Jan 2019 (actual)
- First posted
- 21 Sep 2017 (actual)
- Results
- Posted 15 Jul 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Multiple Sclerosis (MS) is an acquired inflammatory demyelinating disease of the central nervous system (CNS) that is regarded as the foremost cause of non-traumatic neurologic disability in adults in North America. Spasticity is a common complication in MS and occurs in up to 84% of patients. The main sign of spasticity is resistance to passive limb movement characterized by increased resistance to stretching, clonus, and exaggerated deep reflexes. Osmotica Pharmaceutical is currently developing arbaclofen extended-release tablets (AERT) for the treatment of spasticity in patients with MS.
Detailed description
This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the safety and efficacy of oral AERT in MS patients with spasticity. Two doses of AERT, 40 mg and 80 mg, will be compared with placebo. The treatment groups will be randomized in a 1:1:1 ratio. Eligible patients will undergo a washout period for withdrawal of all medications used for anti-spasticity and/or muscle relaxation prior to randomization. A baseline clinical evaluation will be performed (Visit 2) to confirm eligibility for study randomization, and subjects will be randomly assigned to 1 of 3 treatment arms. Subjects will remain on maintenance treatment for approximately 3 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| AERT 40 mg | Active comparator | Drug: Arbaclofen40 mg Arbaclofen Extended-Release Tablets |
| AERT 80 mg | Active comparator | Drug: Arbaclofen80 mg Arbaclofen Extended-Release Tablets |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Subjects 18 to 65 years of age, inclusive.
- An established diagnosis of MS that manifests a documented history of spasticity.
- If receiving disease-modifying medications (eg, interferons approved for MS, glatiramer acetate, natalizumab, fingolimod, or mitoxantrone), there must be no change in dose for at least 3 months prior to Visit 1 (Screening), and the subject must be willing to maintain this treatment dose for the duration of the study. If receiving AMPYRA® (dalfampridine, fampridine, 4-amino puridine), subject must be at a stable dose for at least 3 months prior to Visit 1.
- Stable regimen for at least 3 months prior to Visit 2 for all medications and non-pharmacological therapies that are intended to alleviate spasticity.
- Absence of infections, peripheral vascular disease, painful contractures, advanced arthritis, or other conditions that hinder evaluation of joint movement.
Key exclusion criteria (6 listed)
- Any concomitant disease or disorder that has symptoms of spasticity or that may influence the subject's level of spasticity.
- 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.
- Subject has clinically significant abnormal laboratory values, in the opinion of the investigator, at Visit 1 or Visit 2.
- Current malignancy or history of malignancy that has not been in remission for more than 5 years, except effectively treated basal cell skin carcinoma.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ArbaclofenAlso: AERTArbaclofen Extended Release Tablet | Drug | AERT 40 mg, AERT 80 mg |
| PlaceboPlacebo comparator | Drug | Placebo |
Primary outcome
Change From Baseline in Total Numeric-transformed Modified Ashworth Scale Score of the Most Affected Limb (TNmAS-MAL)
Time frame: 84 days
Total Numeric-Transformed Modified Ashworth Scale (TNmAS) is a 6-point scale to measure abnormality in tone or the resistance to passive movements. Higher score is worse outcome. For each joint, the minimum score is 0; maximum score is 5. The values for each of the 3 main joints are summed for the limb score. The limb with the highest score is the most affected limb (MAL). The highest possible score for a limb is 15. Limb range: 0 to 15. To arrive at total limbs (TL) score the values for all 4 limbs are summed; maximum total limb score is 60. TL range: 0 to 60.
Clinical Global Impression of Change (CGIC)
Time frame: 84 days
The Clinical Global Impression of Change (CGIC) was developed to provide a brief, stand-alone assessment of the clinician's view of the subject's global functioning prior to and after initiating a study medication. The scale ranges from -3 to +3 judging whether the change is significantly worse (-3) to significantly improved (+3). Higher score is better outcome. The CGIC scale will be used to measure the overall change in the subject's condition since starting the study. There is no baseline value because the score is a measure of how the patient changed from baseline (treatment initiation).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Jacobs, MD study director
Vice President
30 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Arbaclofen in people with Multiple Sclerosis and Spasticity, Muscle, run by RVL Pharmaceuticals, Inc. at 30 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 sites in Poland, Bulgaria, Belarus, Croatia, Serbia and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Jul 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Total Numeric-transformed Modified Ashworth Scale Score of the Most Affected Limb (TNmAS-MAL) (time frame: 84 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2022.