Open-Label Trial of Minocycline in Early Multiple Sclerosis: Confirmation of Treatment Benefit

MinoMS-2019

This is an open-label, single-arm clinical trial. Trial participants will include men and women, aged 18-60 years who have had a first demyelinating event within the previous 180 days and who have brain magnetic resonance imaging (MRI) with at least two brain T2 lesions which are at least 3 mm in diameter, and at least one of which is ovoid or periventricular or infra-tentorial. Treatment with minocycline until the endpoint is reached or to a maximum of 24 months or until the last-enrolled participant reaches their 12 month visit.

2020-01-31

2022-12-16

2022-12-31

Terminated

Early phase I

9

Inclusion Criteria: All of the following criteria have to be met for inclusion of a patient into the study: * Age between 18 and 60 years inclusive. The lower age limit has been set because the McDonald criteria may not be valid in children and adolescents.15 The upper limit is set because the specificity of the diagnostic criteria is likely reduced in older individuals. Individuals between ages 51-60 must have CSF oligoclonal bands or spinal MRI changes typical of demyelination. * First focal clinical episode suggestive of demyelinating disease within the previous 180 days (measured from onset of the first symptom to treatment start), based on the appearance of a neurological abnormality, present for at least 24 hours. Objective clinical evidence must be present or documented. Patients will be included irrespective of whether the first clinical demyelinating episode was monosymptomatic (i.e. clinical evidence of a single lesion) or polysymptomatic (i.e. clinical evidence of more than one lesion). The period of 90 days is sufficiently long for case finding and screening procedures and for the patient's decision to participate in the study. In our previous trial the protocol was amended to allow inclusion as late as 180 days after onset, but few participants had onset greater than 90 days before randomization and most CIS trials limited enrolment to within 90 days of onset. * At least two lesions on the T2-weighted brain\* MRI scan with a size of at least 3 mm, at least one of which is ovoid or periventricular or infratentorial. This criterion is required because the presence of MRI abnormalities at the time of the first clinical event affect the probability of developing MS. MRI also increases diagnostic certainty by helping to exclude patients with another etiology (e.g. ischemic or neoplastic causes). MRI eligibility will be determined based on the neuroradiologists clinical report. \*One lesion on spinal MRI may substitute for one brain lesion as per the 2005 McDonald Criteria. * Sexually active women of child-bearing potential must agree to use adequate contraception. * Written informed consent * Be a registered Calgary MS Clinic patient * In addition, participants may be enrolled if, as part of their standard care, they initiated and continued treatment with minocycline 100 mg bid and if, in addition to meeting all the previous inclusion criteria, they: completed all baseline activities after onset of the clinical demyelinating event and before of minocycline initiation, if their baseline MRI was completed within 14 days of minocycline initiation. Exclusion Criteria: Patients are to be excluded from enrolment if they display any of the following: * Any disease other than MS that could better explain the patient's signs and symptoms. * Any previous clinical event reasonably attributable to acute demyelination, regardless of whether medical attention was obtained. * They have had two or more MRI scans at least 30 days apart to evaluate the CIS event prior to screening. This will reduce the risk of enrolling participants already monitored for active disease. * Complete transverse myelitis or bilateral optic neuritis. * Any patient who reaches the 2005 McDMS endpoint by the time of the baseline assessment. This may be based on the occurrence of a new relapse (onset at least 30 days after onset of CIS) or evidence of dissemination in time on the baseline MRI if a previous brain MRI had already been undertaken at least 30 days after onset of CIS. * Clinically significant liver, renal, or bone marrow dysfunction. * Any condition that could interfere with MRI or any other evaluation. * Known allergy or contraindication to gadolinium-DTPA or tetracyclines including estimated GFR (eGFR) less than 60. * Concurrent participation in any clinical therapeutic trial. * Pre-treatment with the following substances prior to study enrolment: IFNß, glatiramer acetate (GA), total lymphoid irradiation, anti-lymphocyte monoclonal antibody treatment \[e.g. anti-CD4, anti-CD52 (alemtuzumab), anti-CD20 or B-cell depleting agents (rituximab, ocrelizumab) and anti-VLA4 (natalizumab)\], teriflunomide, dimethyl fumarate, fingolimod, cladribine, ocrelizumab, mitoxantrone, cyclophosphamide, azathioprine, cyclosporine A, methotrexate, or any other immunomodulating or immunosuppressive drug including other recombinant or non-recombinant cytokines. * Use, within the previous 3 months, of any treatment known to be used for experimental MS treatment except minocycline in the case where minocycline was initiated to treat CIS or early MS. * Any other condition or situation that in the opinion of the investigator would either put the patient at risk of worsening health if enrolled in the trial or

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'interventionModelDescription': 'Non-inferiority Design', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE', 'maskingDescription': 'A blinded physician will complete the neurologic exam and determine the EDSS (and be blinded as to which trial the patient is participating in) and the radiologists reading the MRI scans will be blinded that the MRI scans are part of a clinical trial.'}}, 'enrollmentInfo': {'count': 9, 'type': 'ACTUAL'}}

2023-03-24