파킨슨 병 환자에서 하이드 록시 클로로 퀴인의 효능, 안전성 및 내약성을 평가하는 연구

Inclusion Criteria:

• The subject is ≥35 and ≤80 years of age at the time of informed consent.
• The subject has a clinical diagnosis of PD for at least 6 months and for no longer than 4 years before initiation of screening as confirmed by a neurologist using the MDS Criteria for Parkinson's Disease (Postuma, Berg et al. 2015)
• The subject has a Hoehn and Yahr score ≤2.
• The subject has been on stable doses of PD medications for at least 30 days and the investigator does not anticipate they will require a change of their usual PD medications for a period of 48 weeks.
• The subject has a score ≥24 on the MoCA scale.
• The subject does not have severe motor fluctuations or disabling dyskinesias in the clinical judgment of the investigator (MDS-UPDRS score > 2 on any item IV).
• If a sexually active man or a woman of childbearing potential, the subject agrees to use highly effective birth control or to remain abstinent during the trial and for 30 days after the last dose of HCQ. Acceptable (highly effective) methods of contraception for this study include hormonal contraceptives or implant); intrauterine device or system; complete abstinence from sexual intercourse if this is the subject's usual and preferred lifestyle; or sexual partner with surgical sterilization (e.g., tubal ligation, hysterectomy and/or bilateral oophorectomy, vasectomy).
• The subject is capable of giving signed informed consent, which includes understanding the purpose and risks of the study, compliance with the requirements and restrictions that are listed in the informed consent form (ICF) and this protocol, and authorization to use confidential health information in accordance with national and local subject privacy regulations

Exclusion Criteria:

• The subject has atypical or secondary parkinsonism by medical history or in the opinion of the investigator. Atypical parkinsonism includes, but is not limited to, diagnoses of progressive supranuclear palsy, cortico-basal syndrome, and multiple system atrophy. Secondary parkinsonism includes drug-induced, toxin-induced, postinfectious, posttraumatic, or vascular parkinsonism.
• The subject has a history of (within 60 days before initiation of screening) or has planned upcoming major surgery that could interfere with, or for which the treatment might interfere with, the conduct of the study or that would pose an unacceptable risk to the subject in the opinion of the investigator.
• The subject has any active or chronic disease including but not limited to cardiomyopathy or condition other than PD that could interfere with, or for which the treatment might interfere with, the conduct of the study or pose an unacceptable risk to the subject in the opinion of the investigator based on medical history, physical examination, vital signs, 12-lead ECG, or clinical laboratory tests.
• Minor deviations of laboratory values from the normal range may be acceptable if judged by the investigator to have no/minor clinical relevance.
• The subject has a recent history (last 6 months) of abuse of addictive substances (alcohol, illegal substances), currently uses >21 units of alcohol per week, or is a regular recreational user of sedatives, hypnotics, tranquillizers, or any other addictive agent in the opinion of the investigator.
• The subject is currently pregnant, is planning pregnancy within the timeframe of the study, or is breastfeeding.
• Patient has a history of psoriasis or porphyria.
• The subject has used any of the following medications within 60 days before Baseline: typical or atypical antipsychotics (including, but not limited to, clozapine, pimavanserin, olanzapine, risperidone, and aripiprazole), metoclopramide, prochlorperazine, methyldopa, tetrabenazine, azithromycin, antimalarial drugs, tamoxifen, amiodarone, dapsone, or digoxin.
• The subject has received a vaccination within 14 days before administration of the first dose of IMP.
• The subject has a prior history of or there is a plan to undergo Deep Brain stimulation, brain lesional procedures (i.e., thalamotomy), or focused ultrasound; to initiate gene therapy treatment for PD; or to initiate use of any formulation of intestinal infusion or continuous subcutaneous infusion of PD medications during the following 48 weeks.
• The subject is currently participating in or has participated in an investigational drug study within 3 months or 5 half-lives, whichever is longer; in a therapeutic device study within 3 months before the first dose of IMP; or has previously participated in a gene therapy trial. Concurrent participation in an observational study is acceptable.
• The subject has renal insufficiency as defined by an estimated glomerular filtration rate (eGFR) of <60 mL/min at screening.
• The subject has cirrhosis or any of the following laboratory values at screening: serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 times the upper limit of normal (ULN) or bilirubin >2 × ULN except if the subject has known or suspected Gilbert's disease.
• The subject has a QTcF (QT interval corrected for heart rate by Fridericia's method) value >450 msec if male or >470 msec if female at screening.
• The subject has previously received hydroxychloroquine or has a known allergy or hypersensitivity to hydroxychloroquine or any components of the formulation.
• The subject has a history of bone marrow failure, anemia, aplastic anemia, agranulocytosis, leukopenia, or thrombocytopenia
• The subject has a history of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency
• The subject is unable or unlikely to comply with the dosing schedule or study evaluations in the judgment of the investigator.
• The subject is a member of a protected/vulnerable population, defined as persons who are pregnant, parturient, or breastfeeding; persons who are deprived of liberty; persons who are admitted to a health or social institution for purposes other than research; adults who are under legal protection or who are unable to express their consent; persons who are in an emergency situation and are unable to express their prior consent; and persons are who are non-affiliated or a non-beneficiary of a social security system.
• The subject is a relative of the investigator or sponsor or the relative of an employee of the sponsor.
• The subject has a history of retinopathy or is found to have a significant retina finding on screening ophthalmologic examination.