Minocycline in MS: Confirmation of Benefit

NCT04291456 | Terminated Phase 3

• 1 other identifier: MinoMS-2019
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Multiple Sclerosis; Clinically Isolated Syndrome

Keywords

Multiple Sclerosis; Clinically Isolated syndrome; Minocycline

Outcome Measures

Primary Outcomes (1)

• proportion of participants diagnosed with multiple sclerosis according to the 2005 McDonald Criteria

  The endpoint, Multiple sclerosis, is based on reaching the 2005 diagnostic criteria based on the occurrence of a second relapse or a new or enlarging MRI T2 lesion, or a new gadolinium-enhancing lesion on MRI

  6 months

Secondary Outcomes (2)

• Proportion of participants diagnosed with multiple sclerosis according to the 2005 McDonald Criteria

  3,6, 12 and 24 months

• The proportion of participants with no evidence of disease activity (NEDA)

  3,6,12,and 24 months

Study Arms (1)

Minocycline

EXPERIMENTAL

Minocycline 100 mg oral twice daily for up to 24 month

Drug: Minocycline 100mg

Interventions

Minocycline 100mg DRUG

Single-arm trial of minocycline 100 mg twice daily

Minocycline

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Calgary: lead
• Hotchkiss Brain Institute, University of Calgary: collaborator
• Multiple Sclerosis Society of Canada: collaborator

Study Sites (1)

Calgary MS Clinic at Foothills Medical Centre

Calgary, Alberta, T2N 2T9, Canada

Location

MeSH Terms

Conditions

Multiple Sclerosis; cyclopia sequence

Interventions

Minocycline

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Luanne Metz, MD,FRCPC

  University of Calgary

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Department of Clinical Neurosciences, University of Calgary

Model Details: Non-inferiority Design

Study Record Dates

• First Submitted: November 18, 2019
• First Posted: March 2, 2020
• Study Start: January 31, 2020
• Primary Completion: December 16, 2022
• Study Completion: December 31, 2022
• Last Updated: March 24, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)