- ICH GCP
- Yhdysvaltain kliinisten tutkimusten rekisteri
- Kliininen tutkimus NCT07666022
A Clinical Study to Evaluate the Safety of MF1, a New Treatment for Parkinson's Disease-related Disorders (MF1 Study)
A Phase I Investigator-initiated First-in-human Study to Evaluate the Safety and Pharmacokinetics of MF1 in Healthy Adults and Patients With Parkinson's Disease (MF1-FIH)
This is a Phase I, investigator-initiated, first-in-human study to evaluate the safety, tolerability, and pharmacokinetics of MF1, a novel agent that is expected to inhibit α-synuclein related pathogenesis in α-synucleinopathies, primarily Parkinson's disease (PD). MF1 aims to address the unmet medical need in PD, which affects about 1% of individuals aged 60 years and older in Japan and is projected to reach 43 million patients worldwide by 2050.
The trial consists of three parts: Part A (single ascending dose) and Part B (multiple ascending dose) in healthy Japanese male adults, and Part C (multiple dose) in patients with idiopathic PD. Part A is a randomized, double-blind, placebo-controlled, single-center study assessing single oral doses , including a food-effect evaluation. Part B is a randomized, double-blind, placebo-controlled, single-center study with once-daily dosing for 7 days. Part C is an open-label, multicenter study in 4-8 PD patients (MDS 2015 criteria, Hoehn & Yahr stage ≤3) receiving once daily for 14 days, with or without stable background antiparkinsonian therapy.
The primary objective is to assess safety and tolerability; secondary objectives include characterization of plasma, urine, and cerebrospinal fluid pharmacokinetics and assessment of food effect. Exploratory pharmacodynamic endpoints include biomarkers such as α-synuclein, neurofilament light chain, UCHL-1, FABP3, GFAP, and other neurodegeneration markers.
Key exclusion criteria include clinically significant systemic diseases, seizure history, serious infections (HBV, HCV, HIV, syphilis), recent suicidal ideation or attempts, and recent use of other investigational products.
Tutkimuksen yleiskatsaus
Tila
Interventio / Hoito
Yksityiskohtainen kuvaus
- α-Synucleinopathies are a group of progressive neurodegenerative diseases caused by the pathological aggregation and prion-like propagation of α-synuclein protein, culminating in selective neuronal loss. Parkinson's disease (PD) represents the most prevalent form, affecting approximately 1% of individuals aged 60 years and older in Japan, with the global burden projected to reach 43 million patients by 2050. Despite decades of research, currently approved therapies remain restricted to symptomatic management targeting dopaminergic deficits and do not address the underlying mechanisms of α-synuclein misfolding, oligomerization, or cell-to-cell spread. No disease-modifying, neuroprotective, or neurorestorative therapy has been approved to date, representing a critical unmet medical need.
- MF1 is a novel investigational agent designed to target the pathophysiological mechanisms underlying α-synucleinopathy. Preclinical studies have demonstrated that MF1 inhibits α-synuclein aggregation and reduces neuroinflammatory cascades associated with dopaminergic neurodegeneration. Based on its mechanism of action, MF1 is expected to be a novel therapeutic agent targeting these pathological mechanisms, with the potential to confer both neuroprotective effects and clinically meaningful symptomatic benefits, thereby addressing this unmet medical need.
- This First-in-Human (FIH) Phase I trial employs a stepwise dose-escalation approach across three sequential parts to characterize the safety, tolerability, and pharmacokinetic (PK) profile of MF1. The three-part sequential dose-escalation design, incorporating single ascending doses (Part A) and multiple ascending doses (Part B) in healthy adult volunteers, followed by evaluation in a patient cohort (Part C), is consistent with established first-in-human (FIH) best practices and ensures systematic safety data review prior to advancement to each subsequent study part.
- The restriction to healthy Japanese males aged 18-44 years with BMI 18.5 to <25.0 kg/m² in Parts A and B is intended to minimize confounding variables during initial safety and PK characterization. Given that MF1 is intended for a patient population with a higher average age and potential co-morbidities, Part C enrolls patients with idiopathic PD under a more inclusive age range (40-84 years) and permits concomitant use of select stable antiparkinsonian medications to reflect real-world treatment conditions. The restriction to Hoehn & Yahr stage ≤3 ensures that participants retain sufficient functional capacity for protocol compliance and limits confounding from advanced disease-related physiological changes.
- Food effect assessment in Part A is incorporated to characterize the influence of food intake on oral bioavailability of MF1, which will inform dosing recommendations for subsequent studies. CSF sampling in a subset of participants is planned to assess CNS penetration of MF1, a critical pharmacological prerequisite for a CNS-targeted agent. Exploratory pharmacodynamic assessments include established fluid biomarkers of neuronal injury and glial activation (α-synuclein, Nf-L, UCHL-1, FABP3, GFAP), which will provide mechanistic evidence of target engagement and serve as early signals for neuroprotective activity.
- The primary objectives of Part C are to assess the safety and tolerability profile in a small number of elderly subjects and to obtain pharmacokinetic data in this patient population, which will serve to support rational dose selection for subsequent phases of clinical development.
Opintotyyppi
Ilmoittautuminen (Arvioitu)
Vaihe
- Vaihe 1
Yhteystiedot ja paikat
Opiskeluyhteys
- Nimi: MASANORI FUJIWARA
- Puhelinnumero: +81 22-717-7136
- Sähköposti: masanori.fujiwara.a5@tohoku.ac.jp
Opiskelupaikat
-
-
Tokyo
-
Sumida-ku, Tokyo, Japani, 130-0004
- Rekrytointi
- Sumida Hospital
-
Ottaa yhteyttä:
- Yu Nemoto, PhD
- Puhelinnumero: +81-22-717-7136
- Sähköposti: yu.nemoto.b8@tohoku.ac.jp
-
Ottaa yhteyttä:
- Masanoir Fujiwara
-
Päätutkija:
- Rie Yazawa, MD
-
-
Osallistumiskriteerit
Kelpoisuusvaatimukset
Opintokelpoiset iät
- Aikuinen
- Vanhempi Aikuinen
Hyväksyy terveitä vapaaehtoisia
Kuvaus
Inclusion Criteria:
(Parts A and B)
- 1)Healthy Japanese male adults aged >=18 and <45 years at the time of informed consent.
- 2) Subjects with a body mass index (BMI) of >=18.5 and <25.0 kg/m2 at screening.
- 3) Subjects who have received sufficient explanation regarding the study from the principal investigator or subinvestigator, have understood the objectives of the study, voluntarily agreed to participate, and have provided written informed consent of their own free will.
(Part C)
- 1) Patients diagnosed with idiopathic Parkinson's disease according to the International Parkinson and Movement Disorder Society (MDS) Clinical Diagnostic Criteria (2015).
- 2) Patients with Parkinson's disease classified as Stage 3 or below according to the modified Hoehn and Yahr staging scale.
- 3) Patients who are either untreated or have been receiving one of the following treatments at a stable dosage regimen for at least 8 weeks prior to screening, with no planned changes during the study period: selegiline up to 5 mg twice daily, rasagiline up to 1 mg once daily, or immediate-release carbidopa/levodopa up to 25/100 mg three times daily.
- 4) Patients with an average Bristol Stool Scale score of <=3 from the date of informed consent to eligibility assessment, or patients with fewer than two bowel movements per week.
If the period between informed consent and eligibility assessment is less than one week, information prior to informed consent will also be collected to assess bowel conditions for at least one week in total.
- 5) Male or female patients aged >=40 and <85 years at the time of informed consent.
- 6) Patients with a BMI of >=18.5 and <32.0 kg/m2 at screening.
- 7) Female patients who are postmenopausal for at least one year at the time of informed consent, including menopause resulting from hysterectomy or oophorectomy.
- 8) Patients who have received sufficient explanation regarding the study from the principal investigator or subinvestigator, have understood the objectives of the study, voluntarily agreed to participate, and have provided written informed consent of their own free will.
Exclusion Criteria:
(Parts A and B)
- 1) Subjects with clinically significant cardiovascular, neurological, pulmonary, hepatic, renal, metabolic, gastrointestinal, urological, immunological, endocrine, or psychiatric disorders, or any other abnormalities that may affect safety, increase seizure risk, lower seizure threshold, or confound study results.
- 2) Subjects with current or past diseases or surgical histories involving the gastrointestinal tract, liver, kidneys, or other organs that may affect drug absorption, metabolism, or excretion.
- 3) Subjects who used any medication, including over-the-counter drugs, within 7 days prior to the day before the first administration of the investigational product.
- 4) Subjects with seizure disorders such as epilepsy, or a history thereof.
- 5) Subjects with allergies or a history of allergies to drugs or foods.
- 6) Subjects with allergic predisposition who are considered unsuitable for participation by the principal investigator or subinvestigator.
- 7) Subjects with current or past alcohol or drug dependence.
- 8) Subjects who donated >=400 mL of whole blood within 12 weeks, >=200 mL of whole blood within 4 weeks, or blood components within 2 weeks prior to investigational product administration.
- 9) Subjects who tested positive at screening for HBs antigen, HCV antibody, HIV antigen/antibody, or syphilis serology (TP antibody test or RPR test).
- 10) Subjects unwilling to use appropriate contraception from the time of informed consent until the final study visit.
- 11) Subjects who answered "Yes" to Question 4 or 5 regarding suicidal ideation on the Columbia-Suicide Severity Rating Scale (C-SSRS) at screening, or who had a history of suicidal behavior within 6 months prior to screening.
- 12) Subjects who received investigational treatment in another clinical trial within 4 months prior to investigational product administration.
- 13) Subjects judged unsuitable for study participation by the principal investigator or subinvestigator based on findings from screening or admission assessments, observations, or examinations.
(Part C)
- 1) Patients with drug-induced parkinsonism, metabolic neurogenetic disorders, encephalitis, Parkinson-plus syndromes, or other atypical parkinsonian syndromes.
- 2) Patients with freezing of gait.
- 3) Patients with a history of stereotactic brain surgery for Parkinson's disease (e.g., pallidotomy, deep brain stimulation, or fetal tissue transplantation).
- 4) Patients with clinically significant cardiovascular, neurological, pulmonary, hepatic, renal, metabolic, gastrointestinal, urological, immunological, endocrine, or psychiatric disorders other than Parkinson's disease, or any other abnormalities that may affect safety, increase seizure risk, lower seizure threshold, or confound study results.
- 5) Patients with current or past diseases or surgical histories involving the gastrointestinal tract, liver, kidneys, or other organs that may affect drug absorption, metabolism, or excretion.
- 6) Patients with seizure disorders such as epilepsy, or a history thereof.
- 7) Patients currently receiving antiplatelet agents or anticoagulants.
- 8) Patients with allergies or a history of allergies to drugs or foods.
- 9) Patients with allergic predisposition who are considered unsuitable for participation by the principal investigator or subinvestigator.
- 10) Patients with current or past alcohol or drug dependence.
- 11) Patients who donated >=400 mL of whole blood within 16 weeks, >=200 mL of whole blood within 4 weeks, or blood components within 2 weeks prior to investigational product administration.
- 12) Patients who tested positive at screening for HBs antigen, HCV antibody, HIV antigen/antibody, or syphilis serology (TP antibody test or RPR test).
- 13) Patients unwilling to use appropriate contraception from the time of informed consent until the final study visit.
- 14) Patients who answered "Yes" to Question 4 or 5 regarding suicidal ideation on the Columbia-Suicide Severity Rating Scale (C-SSRS) at screening, or who had a history of suicidal behavior within 6 months prior to screening.
- 15) Patients who received investigational treatment in another clinical trial within 4 months prior to investigational product administration.
- 16) Patients judged unsuitable for study participation by the principal investigator or subinvestigator based on findings from screening or admission assessments, observations, or examinations.
Opintosuunnitelma
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Ensisijainen käyttötarkoitus: Seulonta
- Jako: Satunnaistettu
- Inventiomalli: Rinnakkaistehtävä
- Naamiointi: Kolminkertaistaa
Aseet ja interventiot
Osallistujaryhmä / Arm |
Interventio / Hoito |
|---|---|
|
Kokeellinen: MF1 single ascending dose (healthy)
Single oral dose of MF1 in healthy male adults (Part A).
|
Oral administration of MF1
|
|
Placebo Comparator: Placebo single dose (healthy)
Single oral dose of placebo in healthy male adults (Part A).
|
Indistinguishable from MF1
|
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Kokeellinen: MF1 multiple ascending doses (healthy)
Once-daily oral doses of MF1 for 7 days in healthy male adults (Part B).
|
Oral administration of MF1
|
|
Placebo Comparator: Placebo multiple doses (healthy)
Once-daily oral doses of placebo for 7 days in healthy male adults (Part B).
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Indistinguishable from MF1
|
|
Kokeellinen: MF1 multiple doses (Parkinson's disease)
Once-daily oral doses of MF1 for 14 days in patients with Parkinson's disease (Part C).
|
Oral administration of MF1
|
Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
Number of participants with treatment-emergent adverse events and serious adverse events
Aikaikkuna: 12 days from last dosing
|
The number and percentage of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) will be summarized by treatment group and study part (Part A, Part B, Part C), including events leading to permanent discontinuation of study drug and clinically significant changes in vital signs, clinical laboratory tests, and 12-lead ECGs.
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12 days from last dosing
|
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Maximum plasma concentration (Cmax) of MF1
Aikaikkuna: 5 days after last dosing
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Cmax will be determined from plasma concentration-time data following single and multiple oral doses of MF1 in healthy subjects (Parts A and B) and patients with Parkinson's disease (Part C)
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5 days after last dosing
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Area under the plasma concentration-time curve from time zero to last measurable concentration (AUC0-t) of MF1
Aikaikkuna: Time Frame: Pre-dose through 5 days after last dosing
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AUC0-t will be calculated using the linear-log trapezoidal method from plasma concentration-time data following single and multiple oral doses of MF1
|
Time Frame: Pre-dose through 5 days after last dosing
|
|
Terminal elimination half-life (t1/2) of MF1
Aikaikkuna: Pre-dose through 5 days after last dosing
|
t1/2 will be calculated from the terminal slope of the plasma concentration-time profile following single and multiple oral doses of MF1
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Pre-dose through 5 days after last dosing
|
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Cerebrospinal fluid (CSF) concentration of MF1
Aikaikkuna: Pre-dose through 24 hours after last dosing
|
CSF concentrations of MF1 will be determined at a predefined time point in healthy participants in single ascending last 2 doses(Part A) and patients with Parkinson's disease (Part C) to assess central nervous system penetration.
|
Pre-dose through 24 hours after last dosing
|
Yhteistyökumppanit ja tutkijat
Sponsori
Yhteistyökumppanit
Opintojen ennätyspäivät
Opi tärkeimmät päivämäärät
Opiskelun aloitus (Todellinen)
Ensisijainen valmistuminen (Arvioitu)
Opintojen valmistuminen (Arvioitu)
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Ensimmäinen Lähetetty (Todellinen)
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Todellinen)
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Viimeksi vahvistettu
Lisää tietoa
Tähän tutkimukseen liittyvät termit
Avainsanat
Muita asiaankuuluvia MeSH-ehtoja
Muut tutkimustunnusnumerot
- C-72
Yksittäisten osallistujien tietojen suunnitelma (IPD)
Aiotko jakaa yksittäisten osallistujien tietoja (IPD)?
IPD-suunnitelman kuvaus
IPD-jakamista tukeva tietotyyppi
- STUDY_PROTOCOL
- MAHLA
- ICF
- ANALYTIC_CODE
- CSR
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