Multiple SclerosisPhase 3OS440-3005NCT03319732
A Study to Evaluate the Long-term Safety of Arbaclofen Extended-Release Tablets for Patients With Spasticity Due to MS
A Phase 3 study testing Arbaclofen in people with Multiple Sclerosis and Spasticity, Muscle, run by RVL Pharmaceuticals, Inc. at 1 site in United States.
Trial summary
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. 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?
- No, everyone receives an active treatment
- How many people
- 323 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Apr 2018to 11 Jun 2020
- 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 per McDonald Criteria (Polman et al 2011) of MS (either relapsing-remitting [RR] or secondary-progressive [SP] course) that manifests a documented history of spasticity for at least 6 months prior to Baseline.
- Has participated in Study OS440-3004 or is a new US subject (ie, a de novo subject) who fulfills the inclusion/exclusion criteria.
- Is willing to continue on open-label treatment with AERT as described in this protocol.
- 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 Baseline, and the subject must be willing to maintain this treatment dose for the duration of the study. If receiving AMPYRA® (dalfampridine, fampridine, 4 amino pyridine), subject must be at a stable dose for at least 3 months prior to Baseline.
- Stable regimen for at least 1 month prior to Baseline for all medications and non pharmacological therapies that are intended to alleviate spasticity.
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- De novo subjects being considered for enrollment and taking medications indicated for the treatment of spasticity (ie, baclofen, benzodiazepines, cannabinoids, carisoprodol, dantrolene, tizanidine, cyclobenzaprine, any neuroleptic, ropinoprole, tolperisone, and clonidine) must wash out from these medications for a minimum of 21 days by Baseline in order to be eligible for study treatment. De novo subjects found not to meet this criterion will be withdrawn from the study and will be considered screen failures.
- Absence of infections, peripheral vascular disease, painful contractures, advanced arthritis, or other conditions that hinder evaluation of joint movement.
- Creatinine clearance, as calculated by the glomerular filtration rate (GFR) using the Modification of Diet in Renal Disease Study (MDRD) formula, of >50 mL/minute.
- Use of a medically highly effective form of birth control (see Section 7.8 of the protocol) during the study and for 3 months thereafter for women of child-bearing potential (including female 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.
- Inability to rate their level of spasticity or distinguish it from other MS symptoms.
- Use of high dose oral or intravenous methylprednisolone, or equivalent, within 3 months before Baseline.
- History of allergy to baclofen or any inactive components of the test formulation.
- Concomitant use of medications that would potentially interfere with the actions of the study medication or outcome variables (Appendix 5).
- Pregnancy, lactation, or planned pregnancy during the course of the study and for 3 months after the final study visit.
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- Recent history (within past 12 months) of any unstable psychiatric disease (or yes response to questions 1 or 2 on the Columbia Suicide Severity Rating Scale [C SSRS] at baseline), or current signs and symptoms of significant medical disorders such as severe, progressive, or uncontrolled pulmonary, cardiac, gastrointestinal, hepatic, renal, genitourinary, hematological, endocrine, immunologic, or neurological disease.
- History of epilepsy.
- Current significant cognitive deficit, severe or untreated anxiety, severe or untreated depression.
- Subjects with abnormal micturition that requires indwelling or intermittent catheterization or with lower urinary tract symptoms (LUTS) that result in a score >26 in the Baseline Urinary Symptom Profile - USP© (USP) questionnaire (Appendix 6). Subjects who are proficient in self-catheterization may be included in the study at the investigator's discretion.
- Current malignancy or history of malignancy that has not been in remission for more than 5 years, except effectively treated basal cell skin carcinoma.
- Subject has clinically significant abnormal laboratory values, in the opinion of the investigator at Baseline (at Visit 6 for rollover subjects).
- Any other significant disease, disorder, or significant laboratory finding, including clinically significant abnormal laboratory values or ongoing serious adverse events (SAEs) at Visit 6 (Final Visit) of Study OS440-3004, 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.
- Planned elective surgery or other procedures requiring general anesthesia during the course of the study.
- History of any illicit substance abuse (eg, alcohol, marijuana, cocaine) or prescription for long-acting opioids within the past 12 months (tramadol use will be allowed).
- Participation in another clinical research study (with the exception of Study OS440-3004) within 1 month of Baseline.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-Label Study to Evaluate the Long-Term Safety of Arbaclofen Extended-Release Tablets in Multiple Sclerosis Patients With Spasticity (Study OS440-3005)
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, open-label, long-term extension study to evaluate the safety and tolerability of oral AERT in patients with spasticity due to MS. Subjects from the double blind study (Study OS440-3004) may rollover into this open-label extension study, as well as de novo subjects. The maintenance dose will be 80 mg/day or the highest tolerated dose. Once the subject has reached the maintenance dose, they will remain on that dose for approximately 1 year.
- Conditions
- Multiple Sclerosis, Spasticity, Muscle
- Being tested
- Arbaclofen
- 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 is the active R enantiomer of baclofen.
| Study group | Role | What they receive |
|---|---|---|
| AERT 80 mg | Experimental | Arbaclofen extended release tablet, 20 mg Receives: Drug: Arbaclofen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events, Change in Vital Signs, Clinical Laboratory Test Results, 12-lead ECGs, USP Questionnaire, and C-SSRS Results
Safety and tolerability will be assessed by the monitoring of adverse events volunteered, observed, and elicited by general questions in a non-suggestive manner. Changes in vital signs, clinical laboratory test results, 12-lead ECGs, the urinary symptom profile (USP) questionnaire, and the C-SSRS results will also be assessed.
Measured: over 1 year
Secondary outcomes (3)
Patient Global Impression of Change (PGIC)
Patient Global impression of Change (PGIC) is a scale to evaluate the change in activity limitations, symptoms, emotions, and overall quality of life using scores from 1 to 7 with 1 being no change and 7 being a great deal better, and a considerable improvement that has made all the difference. Minimum value is 1 and the maximum value is 7.
Measured: week 60
Total Numeric-transformed Modified Ashworth Scale Score or the Most Affected Limb (TNmAS-MAL)
The abbreviated scale title is TNmAS. It is considered the primary clinical measure of muscle spasticity in subjects with neurological conditions. It is a useful 6-point rating scale (0 to 5) to measure abnormality in tone or the resistance to passive movements. Minimum value is 0 and maximum value is 5. A higher score means a worse outcome.
Measured: week 28
Expanded Disability Status Scale (EDSS)
Expanded Disability Status Scale (EDSS) is a method of quantifying disability in MS and monitoring changes in the level of disability over time. The EDSS scale ranges from 0 to 10 in 0.5-unit increments that represent higher levels of disability. A score of 0 represents a normal neurological exam, and 10 represents death due to MS.
Measured: week 60
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2017
- Study start3 Apr 2018
- Primary completion27 Jan 2020
- Study completion11 Jun 2020
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.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 323 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
- NCT03319732
- Sponsor's protocol ID
- OS440-3005
- Acronym
- OS440-3005
- Status last verified
- Feb 2022
- First submitted
- 13 Oct 2017
- Last updated
- 9 Aug 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Okuda DT, Kantor D, Jaros M, deVries T, Hunter S. Arbaclofen extended-release tablets for spasticity in multiple sclerosis: open-label extension study. Brain Commun. 2023 Feb 7;5(1):fcad026. doi: 10.1093/braincomms/fcad026. eCollection 2023.
PubMed 36861013
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Study to Evaluate the Long-Term Safety of Arbaclofen Extended-Release Tablets in Multiple Sclerosis Patients With Spasticity (Study OS440-3005)
- ClinicalTrials.gov ID
- NCT03319732
- Acronym / sponsor ID
- OS440-3005 / OS440-3005
- Conditions
- Multiple Sclerosis, Spasticity, Muscle
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 323 participants (actual)
- Lead sponsor
- RVL Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Osmotica Pharmaceutical US LLC
- Study start
- 3 Apr 2018 (actual)
- Primary completion
- 27 Jan 2020 (actual)
- Study completion
- 11 Jun 2020 (actual)
- First posted
- 24 Oct 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.
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, open-label, long-term extension study to evaluate the safety and tolerability of oral AERT in patients with spasticity due to MS. Subjects from the double blind study (Study OS440-3004) may rollover into this open-label extension study, as well as de novo subjects. The maintenance dose will be 80 mg/day or the highest tolerated dose. Once the subject has reached the maintenance dose, they will remain on that dose for approximately 1 year.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AERT 80 mg | Experimental | Drug: ArbaclofenArbaclofen extended release tablet, 20 mg |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Subjects 18 to 65 years of age, inclusive.
- An established diagnosis per McDonald Criteria (Polman et al 2011) of MS (either relapsing-remitting [RR] or secondary-progressive [SP] course) that manifests a documented history of spasticity for at least 6 months prior to Baseline.
- Has participated in Study OS440-3004 or is a new US subject (ie, a de novo subject) who fulfills the inclusion/exclusion criteria.
- Is willing to continue on open-label treatment with AERT as described in this protocol.
- 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 Baseline, and the subject must be willing to maintain this treatment dose for the duration of the study. If receiving AMPYRA® (dalfampridine, fampridine, 4 amino pyridine), subject must be at a stable dose for at least 3 months prior to Baseline.
Key exclusion criteria (16 listed)
- Any concomitant disease or disorder that has symptoms of spasticity or that may influence the subject's level of spasticity.
- Inability to rate their level of spasticity or distinguish it from other MS symptoms.
- Use of high dose oral or intravenous methylprednisolone, or equivalent, within 3 months before Baseline.
- History of allergy to baclofen or any inactive components of the test formulation.
- Concomitant use of medications that would potentially interfere with the actions of the study medication or outcome variables (Appendix 5).
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 is the active R enantiomer of baclofen. | Drug | AERT 80 mg |
Primary outcome
Number of Participants With Adverse Events, Change in Vital Signs, Clinical Laboratory Test Results, 12-lead ECGs, USP Questionnaire, and C-SSRS Results
Time frame: over 1 year
Safety and tolerability will be assessed by the monitoring of adverse events volunteered, observed, and elicited by general questions in a non-suggestive manner. Changes in vital signs, clinical laboratory test results, 12-lead ECGs, the urinary symptom profile (USP) questionnaire, and the C-SSRS results will also be assessed.
3 secondary outcomes
Patient Global Impression of Change (PGIC)
Time frame: week 60
Total Numeric-transformed Modified Ashworth Scale Score or the Most Affected Limb (TNmAS-MAL)
Time frame: week 28
Expanded Disability Status Scale (EDSS)
Time frame: week 60
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36861013Okuda DT, Kantor D, Jaros M, deVries T, Hunter S. Arbaclofen extended-release tablets for spasticity in multiple sclerosis: open-label extension study. Brain Commun. 2023 Feb 7;5(1):fcad026. doi: 10.1093/braincomms/fcad026. eCollection 2023.
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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
1 site in 1 country: 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 1 site in United States.
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 11 inclusion and 16 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 9 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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. 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?
Number of Participants With Adverse Events, Change in Vital Signs, Clinical Laboratory Test Results, 12-lead ECGs, USP Questionnaire, and C-SSRS Results (time frame: over 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03319732, which also lists 1 linked publication.
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 9 Aug 2022.