(S)-N-(5-(4-(1-(BENZO[D][1,3]DIOXOL-5-YL)ETHYL)PIPERAZIN-1-YL)-1,3,4-THIADIAZOL-2-YL)ACETAMIDE, HYDROCHLORIDE SALT for Progressive supranuclear palsy

Inclusion criteria

• {"criterion_text":"- Able to understand and willing to provide informed consent prior to entry into the study and able to comply with the study procedures and restrictions.\n- Has a caregiver or study partner who will accompany them to the study visits. The caregiver or study partner must be a person who has frequent contact (at least 7 hours per week at 1 time or in different days) with the participant and is able to provide information about the participant`s medication and overall condition. Prior to the conduct of any study procedures, the caregiver or study partner must be willing to sign the independent ethics committee (IEC)/institutional review board (IRB) approved informed consent.\n- Women of childbearing potential (WOCBP) (Appendix 19.2) or fertile males with partners of childbearing potential must agree to use highly effective contraception (per CTFG 2014) from enrollment (signed consent) through 30 days after the last dose of the IP.\n- Male or female participants aged 50 to 80 years, inclusive, at the time of informed consent.\n- Diagnosis of possible or probable PSP-RS phenotypes according to the MDS PSP clinical features criteria (Höglinger et al 2017). At least 1 (either 1 or both) of the following 2 items must be met: 1. Vertical supranuclear gaze palsy. 2. Slowing of vertical saccades AND postural instability with falls within the first 3 years of PSP symptoms.\n- Presence of PSP symptoms within ≤3 years prior to screening.\n- Full 28-item PSPRS score ≤40.\n- Able to ambulate independently or with minimal assistance defined as the ability to take at least 10 steps (stabilization of 1 arm [ie, use of cane]).\n- MoCA score ≥23.\n- Body weight range ≥43 kg/95 lbs to ≤120 kg/265 lbs.\n- Reside outside a skilled nursing facility or dementia care facility, except for participants residing in an assisted living facility."}

Exclusion criteria

• {"criterion_text":"- Score of 3 on any functional domain in the PSP-CDS.\n- Active chronic inflammatory disease (ie, rheumatoid arthritis, systemic lupus, erythematosus, Crohn’s disease, etc.) which requires chronic treatment not allowed in the study.\n- Participant has significant current suicidal ideation or within 1 year prior to screening as evidenced by answering “yes” to questions 4 or 5 on the suicidal ideation portion of the C-SSRS completed at screening or a history of suicidal attempts within the last 2 years.\n- Current diagnosis or history of drug or alcohol abuse (according to DSM-5 criteria) within the last 2 years prior to screening visit.\n- Any condition that in the judgment of the investigator would interfere with the ability to complete the study (including IP intake), pose significant risk to participant safety, or potentially confound interpretation of study results.\n- Presence of renal impairment as indicated by a creatinine clearance of less than 50 mL/min at screening.\n- Presence of clinically significant hepatic disease; hepatitis or biliary tract disease as indicated by alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels ≥3×upper limit of normal (ULN), bilirubin levels ≥2×ULN at screening, in the absence of Gilbert’s Syndrome. In the event elevated bilirubin levels are suspected to be due to Gilbert’s Syndrome, exclusion decision will be taken in consultation with the medical monitor. The ultimate decision to exclude the participant will be made by the investigator.\n- History of sensitivity to excipients.\n- Participants with known PSP genetic mutation (based on familiar or clinical history).\n- Evidence of other neurological disorder that could explain signs of PSP (eg, Parkinson's disease, Alzheimer disease, etc.).\n- Brain MRI within 1 year of screening consistent with: a.\tPrimary degenerative diseases other than PSP. b.Cerebrovascular disease such as prior hemorrhage or infarct larger than 1 cm; major, strategic, or multiple lacunar infarcts; or extensive white matter lesions scoring 3 in the Wahlund scale (Wahlund et al 2001). Ischemic or hemorrhagic lesions in the substantia nigra, nigrostriatal pathway, brainstem and the basal ganglia would be strategic and would be exclusionary. Other lacunar infarcts will not be considered exclusionary.\n- Diagnosis of any of the following psychiatric disorders: schizophrenia, schizoaffective disorder, bipolar disorder I, or alcohol abuse or dependence per Diagnostic and Statistical Manual of Mental Disorders-5th edition (DSM-5) criteria.\n- Diagnosis of epilepsy.\n- Ongoing infectious, metabolic, or systemic diseases affecting the CNS (ie, syphilis, untreated hypothyroidism, current vitamin B12 or folate deficiency, potentially clinically significant serum electrolyte disturbances, unstable diabetes mellitus, or other similar conditions, including history of human immunodeficiency virus.\n- Significant (ongoing or within 1 year of screening) cardiovascular disease (ie, medical history of stroke, acute coronary syndrome, heart infarction, unstable angina, angina pectoris, ST segment elevation myocardial infarction (STEMI), non-STEMI, transient ischemic attacks, heart failure (New York Heart Association class III or IV), peripheral vascular intervention, atrial fibrillation, clinically relevant cardiac arrhythmias, or uncontrolled hypertension), or at risk of stroke or heart attack.\n- Blood pressure or ECG parameters at screening: a. Seated systolic blood pressure <90 mmHg or >150 mmHg; or diastolic blood pressure <50 mmHg or >90 mmHg. b. ECG abnormalities including: clinically significant conduction abnormalities, ischemic changes (ie, prior Q-wave myocardial infarction and/or marked ischemic ST- and T-wave), arrhythmias (eg, persistent or paroxysmal ventricular or supraventricular arrhythmias, including atrial fibrillation), or other ECG abnormalities that would pose unnecessary risk in the opinion of the investigator."}

Primary endpoints

• {"endpoint_text":"- European regulatory authority (EMA): Change from baseline to Week 52 in the total score of the full 28-item PSPRS outcome.","definition_or_measurement_approach":"Change from baseline to Week 52 in total score of the full 28-item Progressive Supranuclear Palsy Rating Scale (PSPRS)."}
• {"endpoint_text":"- US regulatory authority (FDA): Change from baseline to Week 52 in the total score of the mPSPRS-10 outcome.","definition_or_measurement_approach":"Change from baseline to Week 52 in total score of the modified 10-item PSPRS (mPSPRS-10)."}
• {"endpoint_text":"- Safety endpoints: Safety will be assessed over a treatment period of 52 weeks for the incidence of TEAEs and SAEs, including clinically significant changes in vital signs, clinical laboratory evaluations (including hormone markers in male participants), physical examination findings, ECG parameters, and suicidal ideation/behavior (Columbia Suicide Severity Rating Scale [C SSRS]).","definition_or_measurement_approach":"Incidence and characterization of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) over 52 weeks; monitoring of vital signs, clinical laboratory evaluations (including hormone markers in males), physical exams, ECG parameters, and C-SSRS assessments for suicidal ideation/behavior."}

Secondary endpoints

• {"endpoint_text":"- Change from baseline to Week 52 in Clinician Global Impression of Severity scale (CGI-S).","definition_or_measurement_approach":"Change from baseline to Week 52 measured by the Clinician Global Impression of Severity (CGI-S) scale."}
• {"endpoint_text":"- Change from baseline to Week 52 in Patient Global Impression of Severity Scale (PGI-S).","definition_or_measurement_approach":"Change from baseline to Week 52 measured by the Patient Global Impression of Severity (PGI-S) scale."}
• {"endpoint_text":"- Change from baseline to Week 52 in Caregiver Global Impression of Severity scale (CaGI-S).","definition_or_measurement_approach":"Change from baseline to Week 52 measured by the Caregiver Global Impression of Severity (CaGI-S) scale."}
• {"endpoint_text":"- Slope of decline in PSPRS.","definition_or_measurement_approach":"Rate/slope of change over time in PSPRS scores across study visits."}
• {"endpoint_text":"- Change from baseline to Week 52 in individual subitems of PSPRS.","definition_or_measurement_approach":"Change from baseline to Week 52 in individual PSPRS subitems (each subitem of the PSPRS assessed separately)."}
• {"endpoint_text":"- Change from baseline to Week 52 in Schwab and England Activities of Daily Living Scale (SE-ADL).","definition_or_measurement_approach":"Change from baseline to Week 52 measured by the Schwab and England Activities of Daily Living Scale (SE-ADL)."}
• {"endpoint_text":"- Change from baseline to Week 52 in Progressive Supranuclear Palsy Clinical Deficits Scale (PSP-CDS).","definition_or_measurement_approach":"Change from baseline to Week 52 measured by the PSP Clinical Deficits Scale (PSP-CDS)."}
• {"endpoint_text":"- Change from baseline to Week 52 in Montreal Cognitive Assessment (MoCA).","definition_or_measurement_approach":"Change from baseline to Week 52 measured by the Montreal Cognitive Assessment (MoCA)."}
• {"endpoint_text":"- Change from baseline to Week 52 in Progressive Supranuclear Palsy Quality of Life scale (PSP-QoL).","definition_or_measurement_approach":"Change from baseline to Week 52 measured by the PSP Quality of Life (PSP-QoL) scale."}
• {"endpoint_text":"- PK characterization of FNP-223 and active metabolite.","definition_or_measurement_approach":"Pharmacokinetic profiling of FNP-223 and its active metabolite (blood sampling/PK analyses as specified in protocol)."}

Methods

• Informational Website (Informational Website_Bilingual documents present) — country-specific bilingual informational websites referenced (documents associated with country part II submissions: Italy, Spain, Germany, France, Poland, Portugal, Hungary).
• Digital outreach / Digital Outreach_Bilingual / Participant Recruitment Digital Outreach — digital outreach materials referenced (country-specific versions present for multiple Member States).
• Social media advertising (Facebook and Google ads) — 'Facebook and Google Adv_Bilingual' recruitment material referenced (digital advertising channel).
• Patient brochure / Patient Brochure (country-specific patient brochures) — patient-facing brochures for potential participants referenced for multiple countries.
• Dear Patient Letter — localized 'Dear Patient Letter' recruitment material referenced (country-specific).
• Dear Colleague Letter — clinician-targeted recruitment ('Dear Colleague Letter') referenced (Hungary example present).
• ICF Flipbook / ICF materials — informed consent flipbook and related subject information materials referenced (country-specific).
• Study Fact Sheet — country-specific study fact sheets referenced (Hungary example present).
• Privacy notices, legal notices and cookies policies — supporting recruitment materials referenced for country-specific informational websites and digital outreach.

Italy

Earliest CTIS Part Ii Submission Date

16-08-2024

Latest Decision Or Authorization Date

16-12-2025

Processing Time Days

487

Number Of Sites

5

Number Of Participants

46

Hungary

Earliest CTIS Part Ii Submission Date

16-07-2024

Latest Decision Or Authorization Date

16-12-2025

Processing Time Days

518

Number Of Sites

1

Number Of Participants

13

Poland

Earliest CTIS Part Ii Submission Date

16-08-2024

Latest Decision Or Authorization Date

16-12-2025

Processing Time Days

487

Number Of Sites

2

Number Of Participants

19

Portugal

Earliest CTIS Part Ii Submission Date

22-07-2024

Latest Decision Or Authorization Date

16-12-2025

Processing Time Days

512

Number Of Sites

2

Number Of Participants

22

France

Earliest CTIS Part Ii Submission Date

05-09-2024

Latest Decision Or Authorization Date

16-12-2025

Processing Time Days

467

Number Of Sites

5

Number Of Participants

29

Germany

Earliest CTIS Part Ii Submission Date

20-08-2024

Latest Decision Or Authorization Date

16-12-2025

Processing Time Days

483

Number Of Sites

4

Number Of Participants

11

Spain

Earliest CTIS Part Ii Submission Date

16-08-2024

Latest Decision Or Authorization Date

05-05-2026

Processing Time Days

627

Number Of Sites

11

Number Of Participants

43

Primary sponsor

Full Name

Ferrer Internacional S.A.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Spain

Contract research organisations

Name

Eresearchtechnology Inc.

Responsibilities

eCOA data capture; sponsorDuties codes (15,7)

Name

Icon Clinical Research Limited

Responsibilities

Multiple sponsor duties (codes 1,2,3,4,5,6,8,9,10,11,12,13) as listed in sponsor third-party entry

Name

Anapharm Europe S.L.

Responsibilities

Biomarker Assessment

Name

PCI Pharma Services Germany GmbH

Responsibilities

Sponsor duty code 14

Third parties

• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"eCOA data capture; sponsorDuties codes present (15,7)","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Sponsor duties codes: 1,10,11,12,13,2,3,4,5,6,8,9 (roles per sponsorDuties list)","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Anapharm Europe S.L.","duties_or_roles":"Biomarker Assessment (sponsorDuties code 15)","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"PCI Pharma Services Germany GmbH","duties_or_roles":"Sponsor duties code: 14","organisation_type":"Pharmaceutical company"}