PROSPER: clinical Phase 2 study to test how safe and effective is a new medicine called FNP-223 to slow disease progression of progressive supranuclear palsy (PSP)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ferrer Internacional S.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

25 Sep 2024 → ongoing

Decision date (initial)

2024-09-13

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Ferrer Internacional, S.A.

External identifiers

EU CT number

2023-510366-28-00

ClinicalTrials.gov

NCT06355531

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacokinetic

1. To assess the efficacy of FNP-223 in slowing disease progression in participants with PSP as measured by the PSP Rating Scale (PSPRS) over 52 weeks.
2. To assess the safety and tolerability of FNP-223 for 52 weeks in participants with PSP.

Secondary objectives 4

1. The key secondary objective of the study is: To assess the effects of FNP-223 on the disease severity using a clinical global scale.
2. To assess the effects of FNP-223 on patient and caregiver severity perception of the disease.
3. To investigate the effects of FNP-223 on cognitive function, and additional health-related quality of life parameters.
4. To characterize the pharmacokinetic (PK) profile of FNP-223 and active metabolite in participants with PSP.

Conditions and MedDRA coding

Progressive supranuclear palsy (PSP)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. 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.
2. Male or female participants aged 50 to 80 years, inclusive, at the time of informed consent.
3. 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.
4. Presence of PSP symptoms within ≤3 years prior to screening.
5. Full 28-item PSPRS score ≤40.
6. 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]).
7. MoCA score ≥23.
8. Body weight range ≥43 kg/95 lbs to ≤120 kg/265 lbs.
9. Reside outside a skilled nursing facility or dementia care facility, except for participants residing in an assisted living facility.
10. 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.
11. 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.

Exclusion criteria 16

1. Score of 3 on any functional domain in the PSP-CDS.
2. Participants with known PSP genetic mutation (based on familiar or clinical history).
3. Evidence of other neurological disorder that could explain signs of PSP (eg, Parkinson's disease, Alzheimer disease, etc.).
4. Brain MRI within 1 year of screening consistent with: a. Primary 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.
5. 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.
6. Diagnosis of epilepsy.
7. 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.
8. 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.
9. 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.
10. Active chronic inflammatory disease (ie, rheumatoid arthritis, systemic lupus, erythematosus, Crohn’s disease, etc.) which requires chronic treatment not allowed in the study.
11. 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.
12. Current diagnosis or history of drug or alcohol abuse (according to DSM-5 criteria) within the last 2 years prior to screening visit.
13. 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.
14. Presence of renal impairment as indicated by a creatinine clearance of less than 50 mL/min at screening.
15. 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.
16. History of sensitivity to excipients.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. European regulatory authority (EMA): Change from baseline to Week 52 in the total score of the full 28-item PSPRS outcome.
2. US regulatory authority (FDA): Change from baseline to Week 52 in the total score of the mPSPRS-10 outcome.
3. 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]).

Secondary endpoints 10

1. Change from baseline to Week 52 in Clinician Global Impression of Severity scale (CGI-S).
2. Change from baseline to Week 52 in Patient Global Impression of Severity Scale (PGI-S).
3. Change from baseline to Week 52 in Caregiver Global Impression of Severity scale (CaGI-S).
4. Slope of decline in PSPRS.
5. Change from baseline to Week 52 in individual subitems of PSPRS.
6. Change from baseline to Week 52 in Schwab and England Activities of Daily Living Scale (SE-ADL).
7. Change from baseline to Week 52 in Progressive Supranuclear Palsy Clinical Deficits Scale (PSP-CDS).
8. Change from baseline to Week 52 in Montreal Cognitive Assessment (MoCA).
9. Change from baseline to Week 52 in Progressive Supranuclear Palsy Quality of Life scale (PSP-QoL).
10. PK characterization of FNP-223 and active metabolite.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ferrer Internacional S.A.

Sponsor organisation

Ferrer Internacional S.A.

Address

Avinguda Diagonal 549

City

Barcelona

Postcode

08029

Country

Spain

Scientific contact point

Organisation

Ferrer Internacional S.A.

Contact name

Ferrer MedInfo

Public contact point

Organisation

Ferrer Internacional S.A.

Contact name

Ferrer MedInfo

Third parties 4

Locations

7 EU/EEA countries · 28 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 127 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications