Clinical trial NCT03753763: Safinamide for Multiple System Atrophy (MSA)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple System Atrophy
Keywords: MSA, safinamide
Lead sponsor: Zambon SpA
Sponsor class: INDUSTRY
First posted: 2018-11-27
Enrollment: 49
Sex: ALL
Minimum age (years): 30
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

1. Participant must be 30 to 80 years of age inclusive, at the time of signing the informed consent;
2. Participants who are diagnosed (with MRI confirmation) with possible or probable parkinsonian variant of Multiple System Atrophy less than 2 years ago;
3. Participants with an anticipated survival of at least 3 years in the opinion of the investigator;
4. 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;
5. Capable of giving signed informed consent

Exclusion Criteria:

1. History of neurosurgical procedure, including stereotactic surgery;
2. History of Deep Brain Stimulation (DBS);
3. History of bipolar disorder, severe depression, schizophrenia or other psychotic disorder;
4. 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;
5. History of dementia (DSM-V criteria);
6. 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;
7. Active hepatitis B or C;
8. History of human immunodeficiency virus (HIV) infection;
9. Subjects not able to swallow oral medications;
10. Subjects with severe orthostatic symptoms;
11. Impaired ambulation, i.e. falling more than once per week, bedridden patients or confined to a wheelchair during the whole day;
12. Subjects with active malignant neoplasms;
13. Movement disorders other than MSA (e.g. Parkinson Disease, dementia with Lewy bodies, essential tremor, progressive supranuclear palsy, pharmacological or post-encephalic parkinsonism);
14. 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;
15. Not on a stable regime, for at least 4 weeks prior to the randomization (baseline visit), of

    1. 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
    2. dopamine agonist, anticholinergic and/or amantadine.
16. 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;
17. Patients should not have received treatment with an oral or depot neuroleptic within 12 weeks prior to the randomization visit;
18. Use of any investigational drug within 30 days prior to screening or 5 half-lives, whichever is the longest;
19. Montreal Cognitive Assessment (MoCA) ≤ 20;
20. Laboratory assessments showing moderate or severe hepatic impairment (2x ULN);
21. Allergy/sensitivity or contraindications to the investigational medicinal products (IMPs) or their excipients, anticonvulsants, levodopa or other anti-parkinsonian drugs;
22. 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.

Primary outcomes:
measure: TEAEs (Treatment Emergent Adverse Events) and SAEs (Serious Adverse Events)
timeFrame: Throughout the study, from baseline (and at each interim visit) to telephone follow-up visit at 14 week.
Secondary outcomes:
measure: Change From Baseline to Week 12 in the Goniometric Measurement for Anterior Displacement
timeFrame: From baseline to week 12
measure: Change From Baseline to Week 12 in the Goniometric Measurement for Lateral Displacement
timeFrame: From baseline to week 12
measure: Change From Baseline to Week 12 in Unified Multiple System Atrophy Rating Scale (UMSARS), Part II (ITT Population)
timeFrame: From baseline to week 12
measure: Change From Baseline to Week 12 in Unified Multiple System Atrophy Rating Scale (UMSARS), Part II (PP Population)
timeFrame: From baseline to week 12
measure: Change From Baseline to Week 12 in Multiple System Atrophy Health-Related Quality of Life (MSA-QoL) Scale
timeFrame: From baseline to week 12
measure: Change From Baseline to Week 12 in Montreal Cognitive Assessment (MoCA) Scale
timeFrame: From baseline to week 12
measure: Change From Baseline to Week 12 in Unified Dystonia Rating Scale (UDRS)
timeFrame: From baseline to week 12
Other outcomes:
Locations:
city: Bologna
country: Italy
facility: Università di Bologna
city: Brescia
country: Italy
facility: AAST degli Spedali Civili di Brescia
city: Cassino
country: Italy
facility: San Raffaele Cassino
city: Chieti
country: Italy
facility: Fondazione Università "G. D'Annunzio"
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Neurologico Carlo Besta
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria - Università degli Studi della Campania Luigi Vanvitelli
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
city: Pisa
country: Italy
facility: Azienda Opsedaliero Universitaria Pisana
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
city: Salerno
country: Italy
facility: Azienda Ospedaliera Universitaria OO.RR. San Giovanni di Dio - Ruggi d'Aragona
city: Terni
country: Italy
facility: Azienda Ospedaliera Santa Maria di Terni
city: Alicante
country: Spain
facility: Hospital General Universitario de Elche
city: Barakaldo
country: Spain
facility: Hospital de Cruces
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro Majadahonda
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen de Rocio
Study officials:
affiliation: Zambon SpA
name: Charlotte Keywood, MD
role: STUDY_DIRECTOR
References: