Hydroxychloroquine sulfate for Multiple sclerosis | Progressive multiple sclerosis

Inclusion criteria

• {"criterion_text":"- Written informed consent obtained\n- Men and women who are 18-70 years of age at time of consent\n- Patients with PPMS based on the current diagnostic criteria or non-relapsing SPMS (with no relapses in the last 2 years). MS patients whose disease is still classified as RRMS in the clinic, but who have had no evidence of relapse activity in the last 24 months (including new T2 lesions), and who demonstrated signs of disease progression. Disease progression during the last 24 months is determined as follows: increased EDSS score or increase in points in Kurzke’s Functional Systems evaluation, or enlarging T1 lesions in brain MRI during the previous two years determined by visual inspection by the treating neurologist or clinical neuroradiologist or other indication of clinical worsening determined both by the patient and the experienced treating neurologist, indicating an insufficient control of disease progression.\n- Screening Expanded Disability Status Scale (EDSS) score between 3.0 and 7.5 at screening\n- Worsening of MS symptoms or enlarging of T1 lesions in brain MRI during the previous 2 years The worsening of MS symptoms can be indicated as an increase in total EDSS, or as an increase in points in Kurzke’s functional system evaluation over the last two years, or other indication of clinical worsening determined both by the patient and the experienced treating neurologist, indicating an insufficient treatment response. Enlargement of T1 lesions is determined by visual inspection by the treating neurologist or clinical neuroradiologist.\n- Patients must, in the investigator’s opinion, exhibit reliability and physiologic capability (e.g., sufficient vision, hearing, etc.) to comply with all protocol procedures, and have attained an educational achievement of minimum 8th grade\n- Patients must be fluent in the Finnish language"}

Exclusion criteria

• {"criterion_text":"- Patients undergoing treatment with other antimalarial drugs, amiodarone, dapsone or digoxin, other drugs associated with a significant risk for QT prolongation (see Appendix H), systemic glucocorticoids, or immunorupressing drugs mitoxantrone, cyclophosphamide, natalizumab, alemtuzumab or cladribine\n- Patients with moderate or severe renal insufficiency, defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 at the screening visit\n- Patients with indication of liver disease, defined as either plasma alanine transferase (ALT) level > 3 x upper limit normal (ULN) at the screening visit, or total plasma bilirubin > 2 x ULN\n- Active infection with hepatitis B or C virus\n- Patients with known porphyria or psoriasis\n- Patients with known allergy or other intolerability to HCQ, or to gadolinium MRI contrast agent\n- Patients who are unable or unwilling to undergo gadolinium enhanced MRI scans\n- Patients with claustrophobia, or a history of moderate-to-severe anxiety disorder or panic attacks\n- Pregnant or breast-feeding women, and women of child-bearing potential (WOCBP) with heterosexual relationships who are not capable or willing to use highly effective birth control measures according to ICH M3 (R2) guidance, with an annual failure rate of < 1 %. Such methods should be used throughout the trial and for a period of at least 60 days after last trial drug intake.\n- Exposure to more than 10 mSv doses of ionizing radiation, in addition to that obtained from natural sources, in the past 12 months\n- Patients with intolerance to previous PET scans\n- Patients with other neurodegenerative disease or other significant neurological disease than MS (including epilepsy); patients with any generalized seizures within one year of screening are also excluded\n- Participation in another investigational drug trial in the 3 months prior to baseline, or within 4 elimination half-lives of the trial medication, whichever is longer\n- Patients who are using systemically acting glucocorticoids during the study period; use of topical formulations (ointments, nasal sprays, eye drops etc.) is allowed\n- Evidence of current or history of any significant autoimmune disease that, in the opinion of the investigator, could interfere with evaluation of the study results or constitute a health hazard for the participant\n- Evidence of an immune system that is compromised; including, but not limited to, a diagnosis of HIV; or the participant has been splenectomised or has received an organ transplant (corneal transplants excluded)\n- Diagnosis of cancer (haematological or solid tumour) for which the participant is currently being treated, or for which there is evidence of active disease. Participants with local prostate cancer or local dermatological tumours, such as basal or squamous cell carcinoma, may be included\n- Any of the following, according to the judgment of the investigator: a)\tClinically significant abnormal finding of the physical examination, vital signs (including blood pressure and heart rate), ECG, or laboratory value that would jeopardize the patient’s safety while participating in the trial or capability to participate in the trial, or confound the assessments of the trial b)\tSymptomatic/uncontrolled/unstable or clinically relevant concomitant disease or any other clinical condition that would jeopardize the patient’s safety while participating in the trial or capability to participate in the trial, or confound the assessments of the trial c)\tSignificant or unstable physical condition that may require change to concomitant medication or hospitalization that would impact the assessments of the trial d)\tPlanned major surgery requiring withdrawal from study medication for more than 2 weeks during the study period\n- Patients with artificial cardiac pacemaker or other metal implants that might interfere with the MRI procedures; patients with tattoos, history as metal workers or history of metallic foreign objects in the body need to be evaluated by the investigator for MRI-related risks before inclusion in the study\n- Patients with major psychiatric illness in the past 3 years prior to screening (including, but not limited to schizophrenia, bipolar disorder, schizoaffective psychosis and major depressive disorder; patients with mild depression may be included at the investigator’s discretion\n- Any suicidal behavior in the past 1-year period prior to screening or during the screening period\n- Suicidal ideation type 5 in the C-SSRS (i.e. active suicidal thought with plan and intent) in the past 6 months prior to screening or during the screening period; patients with suicidal ideation type 4 in the C-SSRS (i.e. active suicidal thought with intent but without specific plan) in the past 6 months prior to screening or during the screening period may only be included in the study if assessed and documented by a licensed mental health professional that there is no immediate risk of suicide\n- Positive urine test result for drugs of abuse at the screening or baseline visit, unless explained in a manner acceptable by the investigator by the patient’s medical history and concomitant medications\n- Patients whose screening ophthalmological examination shows retinopathy\n- Patients whose screening MRI scan shows gadolinium enhancing lesions\n- Patients with significant abnormal findings other than MS-related in the screening MRI"}

Primary endpoints

• {"endpoint_text":"- Change in proportion of active voxels in supratentorial cerebral white matter (excluding T1 lesions) in the end-of-treatment TSPO-PET images vs. baseline TSPO-PET images in participants with progressive MS treated with HCQ vs. placebo","definition_or_measurement_approach":"Proportion of active voxels in supratentorial cerebral white matter (excluding T1 lesions) measured by TSPO-PET; comparison between end-of-treatment and baseline TSPO-PET images for HCQ-treated participants versus placebo."}

Secondary endpoints

• {"endpoint_text":"- Change in disease progression as measured with Timed 25 Foot Walk (T25FW)\n- Change in hand dexterity as measured with the 9-Hole Peg Test (9HPT)\n- Change in cognition as measured with symbol digit modalities test (SDMT)\n- Change in health-related quality of life, as measured with the RAND 36-Item Health Survey (RAND-36) and Multiple Sclerosis Impact Scale (MSIS-29) questionnaires\n- Change in fatigue, as measured with the Modified Fatigue Impact Scale (MFIS) and Fatigue Severity Scale (FSS) questionnaires\n- Change in MRI volumetric measures in the brain regions of interest\n- Change in T1 and T2 lesion burden using MRI\n- Change in number of TSPO-PET-measurable chronic active lesions\n- Change in proportion of TSPO-PET-detectable active voxels at the rim of chronic lesions (change in proportion of active voxels)\n- Change in proportion of TSPO-PET-detectable active voxels in the NAWM (change in proportion of active voxels)\n- Change in TSPO-PET signal (DVR, distribution volume ratio) at the edges of chronic lesions\n- Change in TSPO-PET signal (DVR) in the NAWM\n- Change in axonal damage as measured by serum neurofilament light chain (NfL) levels in blood\n- Change in astroglial damage as measured by serum glial fibrillary acidic protein (GFAP) levels in blood\n- Change in number of Quantitative susceptibility mapping (QSM)-positive iron rim lesions\n- Change in neuroaxonal damage as measured by diffusion tensor imaging (DTI)-MRI parameters\n- Change in disease progression as measured with Expanded Disability Status Scale (EDSS)\n- Number of Serious Adverse Events","definition_or_measurement_approach":"Endpoints measured using specified clinical tests, questionnaires, imaging and biomarkers as stated: T25FW for ambulation speed; 9HPT for hand dexterity; SDMT for cognition; RAND-36 and MSIS-29 for health-related quality of life; MFIS and FSS for fatigue; MRI volumetric measures and T1/T2 lesion burden by MRI; TSPO-PET measures (number of chronic active lesions, proportion of active voxels at rims and in NAWM, DVR signals) for neuroinflammation; serum NfL and GFAP assays for axonal and astroglial damage; QSM for iron rim lesions; DTI-MRI parameters (FA, MD, AD, RD) for neuroaxonal damage; EDSS for disability progression; Serious Adverse Events counted per standard safety reporting."}

Methods

• K1_Recruitment arrangements_FI (document) — Finland; recruitment arrangements document for the study targeting patients with progressive multiple sclerosis.
• K2_Recruitment leaflet_FI_public — Finland; recruitment leaflet intended for patients (progressive MS).
• K3_Recruitment material_social media_FI — Finland; recruitment via social media channels aimed at patients with progressive MS.

Finland

Earliest CTIS Part Ii Submission Date

04-11-2025

Latest Decision Or Authorization Date

20-11-2025

Processing Time Days

16

Number Of Sites

1

Number Of Participants

34

Primary sponsor

Full Name

Varsinais-Suomen hyvinvointialue

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Finland

Third parties

• {"country":"Finland","full_name":"Mehilaeinen Oy","duties_or_roles":"sponsorDuties codes: 13; 15: Carrying out ophthalmological examination","organisation_type":"Hospital/Clinic/Other health care facility"}