Multiple System AtrophyPhase 2NCT03753763
Safinamide for Multiple System Atrophy (MSA)
A Phase 2 study testing Safinamide Methanesulfonate in people with Multiple System Atrophy, run by Zambon SpA at 19 sites in 2 countries.
Trial summary
The study is a placebo controlled study, with two parallel arms, in which participants will be randomly assigned in a 2:1 ratio to receive either active (200 mg safinamide) or placebo in a double blind manner. Read more about this study
- Who is it for?
- Ages 30 to 80 years
- Conditions the study is for
- Multiple System Atrophy
- What is being tested?
- Safinamide Methanesulfonate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 49 participants
- Where
- 19 sitesin 2 countries
- Study dates
- 29 Oct 2019to 5 Jan 2021
- Phase
- Phase 2
- 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 30 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participant must be 30 to 80 years of age inclusive, at the time of signing the informed consent;
- Participants who are diagnosed (with MRI confirmation) with possible or probable parkinsonian variant of Multiple System Atrophy less than 2 years ago;
- Participants with an anticipated survival of at least 3 years in the opinion of the investigator;
- Female not pregnant, not breastfeeding, and at least one of the following conditions applies:
- Not a woman of childbearing potential OR
- A woman of childbearing potential who agrees to follow the contraceptive guidance during the treatment period and for at least 30 days after the last dose of study intervention;
- Capable of giving signed informed consent
Who cannot join
- History of neurosurgical procedure, including stereotactic surgery;
- History of Deep Brain Stimulation (DBS);
- History of bipolar disorder, severe depression, schizophrenia or other psychotic disorder;
- History of drug and/or alcohol abuse within 12 months prior to screening as defined by the current edition of the Diagnostic and Statistical Manual of Mental Disorders;
- History of dementia (DSM-V criteria);
- Ophthalmologic history including any of the following conditions: albinism, uveitis, retinitis pigmentosa, retinal degeneration, active retinopathy, severe progressive diabetic retinopathy, inherited retinopathy or family history of hereditary retinal disease;
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- Active hepatitis B or C;
- History of human immunodeficiency virus (HIV) infection;
- Subjects not able to swallow oral medications;
- Subjects with severe orthostatic symptoms;
- Impaired ambulation, i.e. falling more than once per week, bedridden patients or confined to a wheelchair during the whole day;
- Subjects with active malignant neoplasms;
- Movement disorders other than MSA (e.g. Parkinson Disease, dementia with Lewy bodies, essential tremor, progressive supranuclear palsy, pharmacological or post-encephalic parkinsonism);
- Any clinically significant or unstable medical or surgical condition that, in the opinion of the investigator, might preclude safe completion of the study or might affect the results of the study;
- Not on a stable regime, for at least 4 weeks prior to the randomization (baseline visit), of
- oral levodopa (including controlled release, immediate release or a combination of controlled release/immediate release), with or without benserazide/carbidopa, with or without addition of a catechol O-methyltransferase (COMT) inhibitor or
- dopamine agonist, anticholinergic and/or amantadine.
- Patients should not have received treatment with monoamine oxidase inhibitors in the 2 weeks prior to the randomization visit, nor treatment with levodopa infusion, pethidine, opiates, opioids, fluoxetine, fluvoxamine in the 4 weeks prior to the randomization visit;
- Patients should not have received treatment with an oral or depot neuroleptic within 12 weeks prior to the randomization visit;
- Use of any investigational drug within 30 days prior to screening or 5 half-lives, whichever is the longest;
- Montreal Cognitive Assessment (MoCA) ≤ 20;
- Laboratory assessments showing moderate or severe hepatic impairment (2x ULN);
- Allergy/sensitivity or contraindications to the investigational medicinal products (IMPs) or their excipients, anticonvulsants, levodopa or other anti-parkinsonian drugs;
- Any clinically significant condition which, in the opinion of the Investigator, would not be compatible with study participation or represent a risk for patients while in the study.
Trial locations and contacts
19 sites in 2 countries.
19 sites in 2 countries
Italy11 sites
Università di Bologna
Bologna, 40123
AAST degli Spedali Civili di Brescia
Brescia, 25123
San Raffaele Cassino
Cassino, 03043
Fondazione Università "G. D'Annunzio"
Chieti, 66013
Fondazione IRCCS Istituto Neurologico Carlo Besta
Milan, 20133
Azienda Ospedaliera Universitaria - Università degli Studi della Campania Luigi Vanvitelli
Naples, 80138
Azienda Ospedaliera di Padova
Padova, 35128
Azienda Opsedaliero Universitaria Pisana
Pisa, 56126
Istituto Clinico Humanitas
Rozzano, 20089
Azienda Ospedaliera Universitaria OO.RR. San Giovanni di Dio - Ruggi d'Aragona
Salerno, 84131
Azienda Ospedaliera Santa Maria di Terni
Terni, 05100
Spain8 sites
Hospital General Universitario de Elche
Alicante, 03203
Hospital de Cruces
Barakaldo, 48903
Hospital de la Santa Creu i Sant Pau Barcelona
Barcelona, 08025
Hospital Universitario Gregorio Maranon
Madrid, 28007
Hospital Universitario Puerta de Hierro Majadahonda
Madrid, 28222
Hospital Universitario Ramon y Cajal
Madrid, 28304
Hospital Universitario Virgen Macarena
Seville, 41009
Hospital Universitario Virgen de Rocio
Seville, 41013
About this study
Official title: 12-weeks, Multicentre, Randomized, Double-blind, Placebo-controlled, Exploratory, Pilot Study to Evaluate the Safety and Efficacy of Safinamide 200 mg OD, as add-on Therapy, in Patients With Possible or Probable Parkinsonian Variant of MSA
The study is a placebo controlled study, with two parallel arms, in which participants will be randomly assigned in a 2:1 ratio to receive either active (200 mg safinamide) or placebo in a double blind manner. Study population is patients diagnosed, with possible or probable parkinsonian variant of Multiple System Atrophy who are on a stable treatment of levodopa
Read the detailed description
The overall design is a parallel group, placebo controlled, double blind study. The target population are participants diagnosed with possible or probable parkinsonian variant of Multiple System Atrophy who are on stable doses of levodopa.
Trial participation will be up to a maximum duration of 14 weeks and will comprise a screening period (up to 2 weeks), a 2-week run in period during which subjects will receive 1 tablet (either 100 mg safinamide or matching placebo), followed by a 10-week period, during which study participants will take 2 tablets of study medication (200 mg safinamide or placebo) once daily, taken in the morning in addition to their morning levodopa dose. A telephone follow-up call will be performed 2 weeks after the end of treatment.
- Conditions
- Multiple System Atrophy
- Being tested
- Safinamide Methanesulfonate, Safinamide Methanesulfonate matching placebo
- Keywords
- MSA, safinamide
- Medical subject headings
- Multiple System Atrophy, Thyroid Dyshormonogenesis 2A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Safinamide MethanesulfonateDrug
Also called Xadago
100 mg (free base)
Safinamide Methanesulfonate matching placeboDrug
Also called placebo
100 mg placebo
| Study group | Role | What they receive |
|---|---|---|
| Active | Experimental | Safinamide methanesulfonate film-coated tablets once daily Receives: Drug: Safinamide Methanesulfonate |
| Placebo | Placebo comparator | Safinamide Methanesulfonate matching placebo film-coated tablets once daily Receives: Drug: Safinamide Methanesulfonate matching placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
TEAEs (Treatment Emergent Adverse Events) and SAEs (Serious Adverse Events)
While evaluating safety and tolerability of safinamide, 200 mg od, compared with placebo, severity of TEAEs, their relationship to study drug, their seriousness and their consequences were assessed. TEAEs were defined as adverse events (AEs) that started after the first dose of study drug.
Measured: Throughout the study, from baseline (and at each interim visit) to telephone follow-up visit at 14 week.
Secondary outcomes (7)
Change From Baseline to Week 12 in the Goniometric Measurement for Anterior Displacement
To evaluate the potential efficacy of safinamide 200 mg od, as add-on therapy, on quality of life (change in anterior displacement). The goniometric measurement consists in the posture evaluation of the patient, measuring through a goniometer the angle of the flexion of the trunk. Goniometric measurement of "anterior" displacement was determined using a wall goniometer and expressing the value in degrees in the range of 0 to 90.
Measured: From baseline to week 12
Change From Baseline to Week 12 in the Goniometric Measurement for Lateral Displacement
To evaluate the potential efficacy of safinamide 200 mg od, as add-on therapy, on quality of life (change in anterior displacement). The goniometric measurement consists in the posture evaluation of the patient, measuring through a goniometer the angle of the flexion of the trunk. Goniometric measurement of "lateral" displacement was determined using a wall goniometer and expressing the value in degrees in the range of 0 to 90.
Measured: From baseline to week 12
Change From Baseline to Week 12 in Unified Multiple System Atrophy Rating Scale (UMSARS), Part II (ITT Population)
UMSARS is a validated, disease-specific scale representing the diverse signs and symptoms in MSA. Higher scores on the UMSARS scales mean poorer health.
UMSARS has the following domains:
Part I - Activities of Daily Living score (12 questions ranged in 0-4 [total score 0-48]) that evaluates motor including autonomic activities Part II - Motor Examination score (14 questions, [total score 0-56]) Part III - Autonomic Examination Part IV - Global disability scale ((1=completely independent; 2=not completely independent; 3=more dependent; 4=very dependent; 5=total dependent and helpless).
Only UMSARS Part II total score is reported, which was obtained as the sum of the 14 items in the scale. If any of the items were missing, then the total score was considered missing. Higher scores indicate worse functional situation.
Measured: From baseline to week 12
Change From Baseline to Week 12 in Unified Multiple System Atrophy Rating Scale (UMSARS), Part II (PP Population)
UMSARS is a validated, disease-specific scale representing the diverse signs and symptoms in MSA. Higher scores on the UMSARS scales mean poorer health.
UMSARS has the following domains:
Part I - Activities of Daily Living score (12 questions ranged in 0-4 [total score 0-48]) that evaluates motor including autonomic activities Part II - Motor Examination score (14 questions, [total score 0-56]) Part III - Autonomic Examination Part IV - Global disability scale ((1=completely independent; 2=not completely independent; 3=more dependent; 4=very dependent; 5=total dependent and helpless).
Only UMSARS Part II total score is reported, which was obtained as the sum of the 14 items in the scale. If any of the items were missing, then the total score was considered missing. Higher scores indicate worse functional situation.
Measured: From baseline to week 12
Change From Baseline to Week 12 in Multiple System Atrophy Health-Related Quality of Life (MSA-QoL) Scale
The MSA-QoL is a self-reported questionnaire focusing on MSA-specific symptoms and has a scale ranging from 0 to 160, with 0= 'no problem' and 160= "extreme problem".
Measured: From baseline to week 12
Change From Baseline to Week 12 in Montreal Cognitive Assessment (MoCA) Scale
The Montreal Cognitive Assessment (MoCA) was designed as a tool for rapid screening for mild cognitive impairment. It evaluates different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructive skills, abstraction, calculation and orientation. The administration time of the MoCa is 10 minutes. The MoCA scale ranges from 0 to 30, with higher scores indicating better cognitive functioning.
Measured: From baseline to week 12
Change From Baseline to Week 12 in Unified Dystonia Rating Scale (UDRS)
UDRS consists of a Historical Section, divided into questionnaires about 1) on-dyskinesia and 2) off -dystonia, and an Objective Section, divided into 3) impairment and 4) disability scales. The Historical Section is scored from 0-60, and the Objective section is scored 0-44, where higher scores reflect greater difficulty or impairment.
The Unified Dystonia Rating Scale (UDRS) assesses the motor severity and duration of dystonia in 14 body areas. The total score, obtained as the sum of the severity and duration factors, ranges from 0 to 112. Higher scores indicate worse dystonia.
Measured: From baseline to week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Nov 2018
- Study start29 Oct 2019
- Primary completion5 Jan 2021
- Study completion5 Jan 2021
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 System AtrophyStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Zambon SpA
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Charlotte Keywood, MD, Study director, Zambon SpA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03753763
- Sponsor's protocol ID
- Z7219K01
- Other IDs
- 2018-004145-16, 2018
- Status last verified
- Jul 2021
- First submitted
- 19 Nov 2018
- Last updated
- 13 Oct 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 12-weeks, Multicentre, Randomized, Double-blind, Placebo-controlled, Exploratory, Pilot Study to Evaluate the Safety and Efficacy of Safinamide 200 mg OD, as add-on Therapy, in Patients With Possible or Probable Parkinsonian Variant of MSA
- ClinicalTrials.gov ID
- NCT03753763
- Acronym / sponsor ID
- Z7219K01
- Conditions
- Multiple System Atrophy
- Keywords
- MSA, safinamide
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Zambon SpAIndustry (pharma, biotech, devices)
- Study start
- 29 Oct 2019 (actual)
- Primary completion
- 5 Jan 2021 (actual)
- Study completion
- 5 Jan 2021 (actual)
- First posted
- 27 Nov 2018 (actual)
- Results
- Posted 24 Aug 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study is a placebo controlled study, with two parallel arms, in which participants will be randomly assigned in a 2:1 ratio to receive either active (200 mg safinamide) or placebo in a double blind manner. Study population is patients diagnosed, with possible or probable parkinsonian variant of Multiple System Atrophy who are on a stable treatment of levodopa
Detailed description
The overall design is a parallel group, placebo controlled, double blind study. The target population are participants diagnosed with possible or probable parkinsonian variant of Multiple System Atrophy who are on stable doses of levodopa.
Trial participation will be up to a maximum duration of 14 weeks and will comprise a screening period (up to 2 weeks), a 2-week run in period during which subjects will receive 1 tablet (either 100 mg safinamide or matching placebo), followed by a 10-week period, during which study participants will take 2 tablets of study medication (200 mg safinamide or placebo) once daily, taken in the morning in addition to their morning levodopa dose. A telephone follow-up call will be performed 2 weeks after the end of treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active | Experimental | Drug: Safinamide MethanesulfonateSafinamide methanesulfonate film-coated tablets once daily |
| Placebo | Placebo comparator | Drug: Safinamide Methanesulfonate matching placeboSafinamide Methanesulfonate matching placebo film-coated tablets once daily |
Who may qualify
- Ages
- 30 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Participant must be 30 to 80 years of age inclusive, at the time of signing the informed consent;
- Participants who are diagnosed (with MRI confirmation) with possible or probable parkinsonian variant of Multiple System Atrophy less than 2 years ago;
- Participants with an anticipated survival of at least 3 years in the opinion of the investigator;
- Female not pregnant, not breastfeeding, and at least one of the following conditions applies:
- Capable of giving signed informed consent
Key exclusion criteria (24 listed)
- History of neurosurgical procedure, including stereotactic surgery;
- History of Deep Brain Stimulation (DBS);
- History of bipolar disorder, severe depression, schizophrenia or other psychotic disorder;
- History of drug and/or alcohol abuse within 12 months prior to screening as defined by the current edition of the Diagnostic and Statistical Manual of Mental Disorders;
- History of dementia (DSM-V criteria);
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 |
|---|---|---|
| Safinamide MethanesulfonateAlso: Xadago100 mg (free base) | Drug | Active |
| Safinamide Methanesulfonate matching placeboAlso: placebo100 mg placebo | Drug | Placebo |
Primary outcome
TEAEs (Treatment Emergent Adverse Events) and SAEs (Serious Adverse Events)
Time frame: Throughout the study, from baseline (and at each interim visit) to telephone follow-up visit at 14 week.
While evaluating safety and tolerability of safinamide, 200 mg od, compared with placebo, severity of TEAEs, their relationship to study drug, their seriousness and their consequences were assessed. TEAEs were defined as adverse events (AEs) that started after the first dose of study drug.
7 secondary outcomes
Change From Baseline to Week 12 in the Goniometric Measurement for Anterior Displacement
Time frame: From baseline to week 12
Change From Baseline to Week 12 in the Goniometric Measurement for Lateral Displacement
Time frame: From baseline to week 12
Change From Baseline to Week 12 in Unified Multiple System Atrophy Rating Scale (UMSARS), Part II (ITT Population)
Time frame: From baseline to week 12
Change From Baseline to Week 12 in Unified Multiple System Atrophy Rating Scale (UMSARS), Part II (PP Population)
Time frame: From baseline to week 12
Change From Baseline to Week 12 in Multiple System Atrophy Health-Related Quality of Life (MSA-QoL) Scale
Time frame: From baseline to week 12
Change From Baseline to Week 12 in Montreal Cognitive Assessment (MoCA) Scale
Time frame: From baseline to week 12
Change From Baseline to Week 12 in Unified Dystonia Rating Scale (UDRS)
Time frame: From baseline to week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2021.
- 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.
Charlotte Keywood, MD study director
Zambon SpA
19 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Safinamide Methanesulfonate in people with Multiple System Atrophy, run by Zambon SpA at 19 sites in 2 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 24 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 13 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in Italy, Spain. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 24 Aug 2021). 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?
TEAEs (Treatment Emergent Adverse Events) and SAEs (Serious Adverse Events) (time frame: Throughout the study, from baseline (and at each interim visit) to telephone follow-up visit at 14 week.). 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 13 Oct 2021.