A Study to Evaluate Efficacy, Safety and Tolerability of Hydroxychloroquine in Subjects With Parkinson's Disease

NCT06816810 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: Taller Than PD
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine if hydroxychloroquine is safe to take and whether there is potential for it to slow the progression of PD symptoms. This will be done by comparing how PD symptoms progress throughout the study compared to how people with PD typically progress. Within PD, it is thought that an inflammation response is associated with abnormal forms of a protein called alpha-synuclein in the brain. Individuals who have taken this medication for other conditions have been shown to be less likely to develop PD than people who have not taken this medication. Therefore, it is hoped that the study drug may interrupt the inflammation response and in turn stop/delay the progression of PD.

Conditions

Parkinson&Amp;#39;s Disease

Keywords

Hydroxychloroquine; Neuroinflammation; Neuroprotection; Parkinson

Outcome Measures

Primary Outcomes (2)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  All participants exposed to HCQ at least once will be assessed for: * Incidence and severity of treatment-emergent adverse events (TEAEs) * Relationship of TEAEs to HCQ * Percentage of discontinuations due to adverse events (AEs)

  Throughout enrollment (4 weeks of screening) to the end of treatment at 48 weeks and 4-week safety follow-up.

• Efficacy of Hydroxychloroquine (HCQ) in Delaying Clinical Motor Progression Using MDS-UPDRS Part III

  Another primary clinical outcome is assess change in motor symptom severity, specifically using the movement disorder society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III. A ≥4-point increase (one standard deviation) over 48 weeks will be used as a threshold to assess whether HCQ delays clinical motor progression of PD when compared to historical controls.

  Throughout enrollment to the end of treatment at 48 weeks. MDS-UPDRS Part III will be evaluated at baseline, 24 weeks and 48 weeks.

Secondary Outcomes (7)

• Efficacy of Hydroxychloroquine (HCQ) in Delaying Clinical PD Progression Using CGI-C Scale

  Throughout enrollment to the end of treatment at 48 weeks. CGI-C will be evaluated at baseline, 24 weeks and 48 weeks.

• Efficacy of Hydroxychloroquine (HCQ) in Delaying Clinical PD Progression Using CGI-S Scale

  Throughout enrollment to the end of treatment at 48 weeks. CGI-S will be evaluated at baseline, 24 weeks and 48 weeks.

• Efficacy of Hydroxychloroquine (HCQ) in Delaying Clinical PD Progression Using PGI-S Scale

  Throughout enrollment to the end of treatment at 48 weeks. PGI-S will be evaluated at baseline, 24 weeks and 48 weeks.

• Efficacy of Hydroxychloroquine (HCQ) in Delaying Clinical PD Progression Using PGI-C Scale

  Throughout enrollment to the end of treatment at 48 weeks. PGI-C will be evaluated at baseline, 24 weeks and 48 weeks.

• Change in Quality of Life (QoL) as assessed by the PDQ-8

  Throughout enrollment to the end of treatment at 48 weeks. QoL will be evaluated at baseline, 24 weeks and 48 weeks.

Other Outcomes (2)

• Change in Motor Score as Assessed by the PRIMS Digital Assessment

  Throughout enrollment to the end of treatment at 48 weeks. PRIMS Digital Assessment will be evaluated at baseline, 24 weeks and 48 weeks.

• Change in Motor Function as Assessed by Celestra Gait Assessment

  Throughout enrollment to the end of treatment at 48 weeks. Celestra insole gait assessment will be evaluated at baseline, 24 weeks and 48 weeks.

Study Arms (1)

Hydroxychloroquine Treatment for Early Parkinson's Disease (HCQ-PD)

EXPERIMENTAL

This is an open-label study where 40 participants with early-treated Parkinson's Disease will be receive 200mg of Hydroxychloroquine, orally, twice daily for 48 weeks.

Drug: Hydroxychloroquine (HCQ)

Interventions

Hydroxychloroquine (HCQ) DRUG

The intervention involves hydroxychloroquine (HCQ), administered orally in 200 mg tablets, with a dosing schedule of 200 mg twice daily (400 mg per day). The treatment duration is 48 weeks, after which participants will enter a 4-week safety follow-up period. HCQ will be taken alongside stable doses of Parkinson's disease (PD) medications, with no anticipated changes during the study. Monitoring for adverse events, laboratory assessments, and efficacy evaluations will occur regularly throughout the 12-month period. The study does not include a placebo group or other treatment arms.

Hydroxychloroquine Treatment for Early Parkinson's Disease (HCQ-PD)

Eligibility Criteria

• Age: 35 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead

Study Sites (1)

The Ottawa Hospital

Ottawa, Ontario, K1Y 4E9, Canada

Location

Related Publications (28)

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MeSH Terms

Conditions

Neuroinflammatory Diseases

Interventions

Hydroxychloroquine

Condition Hierarchy (Ancestors)

Nervous System Diseases; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• David Grimes, MD, FRCPC

  The Ottawa Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shawna Reddie

CONTACT

613-798-5555; sreddie@ohri.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2025
• First Posted: February 10, 2025
• Study Start: March 1, 2025
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: February 10, 2025

Record last verified: 2025-02

Locations

CA (1)