Progressive multiple sclerosis MedDRA version: 21.1 Level: PT Classification code 10053395 Term: Progressive multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: Oxiklorin
Product Name: Oxiklorin
Pharmaceutical Form: Tablet
INN or Proposed INN: Hydroxychloroquine sulfate
CAS Number: 747-36-4
Concentration unit: mg milligram(s)
Concentration type: e
Sponsors
Varsinais-Suomen sairaanhoitopiirin kuntayhtymä
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Written informed consent obtained 2.Men and women who are 35-65 years of age at time of consent 3.With Primary Progressive Multiple Sclerosis, according to current diagnostic criteria (Polman et al., 2005) or non-active Secondary Progressive Multiple Sclerosis (nSPMS, with no relapses in the last 2 years) 4.Screening Expanded Disability Status Scale (Kurtzke, 1983) (EDSS) score between 3.5 and 7.0 at screening. 5.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. Enlargement of T1 lesions is determined by visual inspection by the treating neurologist or clinical neuroradiologist. 6.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 7.Patients must be fluent in the Finnish language Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 29 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 1
Exclusion criteria
Exclusion criteria: 1.Patients undergoing treatment with other antimalarial drugs, amiodarone, dapsone or digoxin, other drugs associated with a significant risk for QT prolongation, systemic glucocorticoids, or immunorupressing drugs mitoxantrone, cyclophosphamide, natalizumab, alemtuzumab or cladribine 2.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 3.Patients with known significant spinal cord lesion burden, where clinical worsening is likely due to spinal cord involvement rather than brain involvement. This is assessed by the treating neurologist. 4.Patients with major psychiatric illness in the past 3 years prior to screening 5.Any suicidal behavior in the past 1-year period prior to screening or during the screening period 6.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 7.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 8.Patients whose screening ophthalmological examination shows retinopathy 9.Patients whose screening MRI scan shows gadolinium enhancing lesions 10.Patients with significant abnormal findings other than MS-related in the screening MRI 11.Patients with moderate or severe renal insufficiency 12.Patients with indication of liver disease 13.Active infection with hepatitis B or C virus 14.Patients with known active infection with the SARS-CoV-2 virus within the last 35 days prior to the baseline visit 15.Patients with known porphyria or psoriasis 16.Patients with known allergy or other intolerability to HCQ, or to gadolinium MRI contrast agent 17.Patients who are unable or unwilling to undergo gadolinium enhanced MRI scans 18.Patients with claustrophobia, or a history of moderate-to-severe anxiety disorder or panic attacks 19.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 20.Exposure to experimental radiation in the past 12 months such that radiodosimetry limits would be exceeded by participating in this study 21.Patients with intolerance to previous PET scans 22.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 23.Patients who are using systemically acting glucocorticoids during the study period; use of topical formulations (ointments, nasal sprays, eye drops etc.) is allowed 24.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 subject 25.Evidence of an immune system that is compromised; including, but not limited to, a diagnosis of HIV; or the subject has been splenectomised or has received an organ transplant (corneal transplants excluded) 26.Diagnosis of cancer (haematological or solid tumour) for which the subject is currently being treated, or for which there is evidence of active disease. Subjects with local prostate cancer or local dermatological tumou
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To examine the impact of HCQ treatment on TSPO-PET–measurable microglial activation in supratentorial cerebral white matter (excluding T1 lesions) in a progressive MS patient population, and to evaluate the safety and tolerability of the drug in patients with progressive MS;Secondary Objective: To assess the safety and tolerability of HCQ in the study population for the duration of the study To assess the effect of HCQ on following parameters when compared to placebo group - disease progression measured with T25FW or 9HPT - cognition, measured with neuropsychological evaluation - quality of life or fatigue, measured with the RAND-36, MSIS-29, MFIS and FSS questionnaires - MRI volumetric measures in the lesional and non-lesional brain regions of interest - the number of TSPO-PET-measurable or QSM iron rim+ chronic active lesions - the proportion of TSPO-PET-detectable active voxels at the rim of chronic lesions and in the NAWM (change in proportion of active voxels) - TSPO-PET signal (distribution volume ratio) at the edges of chronic lesions and in the NAWM - sNfL and sGFAP levels in blood - neuroaxonal damage as measured by DTI-MRI parameters To assess the impact of HCQ treatment on brain synaptic density as measured by UCB-J PET in patients with progressive MS ;Primary end point(s): The primary endpoint in this study will be 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 patients with progressive MS treated with HCQ vs. placebo.;Timepoint(s) of evaluation of this end point: Baseline and 12 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): PET-based endpoints -To assess the effect of HCQ on the number of TSPO-PET-measurable chronic active lesions when compared to placebo group -To assess the effect of HCQ on the proportion of TSPO-PET-detectable active voxels at the rim of chronic lesions when compared to placebo group (change in proportion of active voxels) -To assess the effect of HCQ on the proportion of TSPO-PET-detectable active voxels in the NAWM when compared to placebo group (change in proportion of active voxels) -To assess the effect of HCQ on TSPO-PET signal (DVR, distribution volume ratio) at the rim of chronic lesions when compared to placebo group -To assess the effect of HCQ on TSPO-PET signal (DVR, distribution volume ratio) in the NAWM when compared to placebo group -To assess the impact of HCQ treatment on brain synaptic density as measured by 11C-UCB-J PET in patients with progressive MS MRI-based endpoints: -To assess the effect of HCQ on the number of QSM positive iron rim lesions when compared to placebo group -To assess the effect of HCQ on MRI volumetric measures in the brain regions of interest when compared to placebo group -To assess the effect of HCQ on T1 and T2 lesion burden using MRI when compared to placebo group -To assess the effect of HCQ on neuroaxonal damage as measured by DTI-MRI parameters (FA, MD, AD and RD) when compared to placebo group Clinical endpoints: -To assess the safety and tolerability of HCQ in the study population for the duration of the study -To assess the effect of HCQ on disease progression as measured with the T25FW when compared to placebo group -To assess the effect of HCQ on hand dexterity as measured with the 9HPT when compared to placebo group -To assess the effect of HCQ on cognition, as measured with neuropsychological evaluation when compared to placebo group -To assess the effect of HCQ on health-related quality of life, as measured with the RAND-36 and MSIS-29 questionnaires when compared to place | — |
Countries
Finland
Contacts
Public ContactVarsinais-Suomen sairaanhoitopiirin
Varsinais-Suomen sairaanhoitopiirin kuntayhtymä
Outcome results
None listed