Minocycline in Clinically Isolated Syndromes (CIS) and Early Single Relapse Multiple Sclerosis (MS)

Condition(s) targeted: Clinically Isolated Syndromes; Early Single Relapse of Multiple Sclerosis

Intervention: Apo-Minocycline (Drug); Placebo Comparator (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Dr. Luanne Metz

Official(s) and/or principal investigator(s):
Luanne Metz, MD, Principal Investigator, Affiliation: University of Calgary

Overall contact:
Luanne Metz, Doctor, Phone: 403-944-4241, Email: lmetz@ucalgary.ca

The aim of the trial is to demonstrate that 100 mg of oral minocycline twice daily reduces the conversion of CIS to McDonald Criteria MS (McDMS) by an absolute 25% as compared to placebo, over a 6 month follow-up period (primary outcome).

A key secondary outcome is to confirm that this early treatment benefit is maintained at two years.

Official title: A Phase III Double-blind, Randomized, Placebo-controlled Trial of Minocycline in Clinically Isolated Syndromes (CIS) and Early Single Relapse Multiple Sclerosis (MS)

Study design: Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Primary outcome: To demonstrate that 100 mg of oral minocycline twice daily reduces the conversion of CIS to McDonald Criteria MS (McDMS) by an absolute 25% as compared to placebo, over a 6 month follow-up period.

Secondary outcome: To confirm that this early treatment benefit is maintained at two years.

Detailed description:

- Minocycline 100 mg bid orally compared to identical placebo

- Clinically Isolated Syndrome (CIS): Patients with a first clinical demyelinating event

suggestive of multiple sclerosis

- Men and women, aged 18-60y, first event within the previous 180 days; 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 infratentorial.

- Up to 24 months of study drug

- Patients will be discontinued from the study when they convert to McDMS based on the

2005 McDonald definition.

- 12 active Canadian MS Clinics

- A total of 200 patients will be randomized. Because 30% of screened patients with CIS

who are clinically eligible are not expected to meet the MRI criteria for inclusion, up to 280 patients will be screened.

Minimum age: 18 Years. Maximum age: 60 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Age between 18 and 60 years.

- 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 time between the first clinical event and initiation of treatment is reasonably short to prevent loss of patients that convert to MS early. While previous CIS studies required earlier enrolment but these studies found that few (about 5 %) patients have a second relapse within 30-60 days of enrolment so we do not expect this extension of the enrolment period to introduce significant bias.

- 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. MRI eligibility will be determined centrally by the UBC MS/MRI Research Group.

- Sexually active women of child-bearing potential must agree to use adequate

contraception.

- Written informed consent

Exclusion Criteria:

- 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.

- Complete transverse myelitis or bilateral optic neuritis. A waiver can be obtained

for bilateral optic neuritis but must be obtained prior to randomization. Waivers must be approved by 3 neurologists including a member of the Clinical Eligibility / Endpoint Committee, a member of the DSMC, and by an experienced MS neurophthalmologist.

Luanne Metz, Doctor, Phone: 403-944-4241, Email: lmetz@ucalgary.ca

University of Calgary, Calgary Health Region, Calgary, Alberta T2N 4N1, Canada; Recruiting
Judy Wu, Phone: 403-944-2589, Email: Judy.Wu@albertahealthservices.ca
Michael Yeung, Doctor, Principal Investigator

University of Alberta, Edmonton, Alberta T6G 2G3, Canada; Recruiting
Leah White, Phone: 780-407-3928, Email: Leah.White@capitalhealth.ca
Pam Dumont, Phone: 780-407-1491, Email: pam1@ualberta.ca
Gregg Blevins, Principal Investigator

Fraser Health Multiple Sclerosis Clinic, Burnaby, British Columbia V5G 2X6, Canada; Recruiting
Galina Vorobeychik, Phone: 604-412-6405, Email: GVneuroMSclinic@shaw.ca
Tara Martin, Phone: 604-412-6405, Ext: 4, Email: Tara.Martin@fraserhealth.ca
Galina Vorobeychik, Principal Investigator

UBC Hospital, Vancouver, British Columbia V6T 2B5, Canada; Recruiting
Leila Lagroix, Phone: 604-822-1758, Email: leila.lagroix@ubc.ca
Nancy Bogle, Phone: 604-822-0754, Email: nancy.boble@ubc.ca
Tony Traboulsee, Principal Investigator

MS Research Unit, Health Sciences Centre, Winnipeg, Manitoba R3A 1R9, Canada; Recruiting
Barbara Stanger, Phone: 204-787-2905, Email: bstanger@exchange.hsc.mb.ca
James Marriott, Principal Investigator

Dalhousie MS Research Unit, Halifax, Nova Scotia B3H 1V7, Canada; Recruiting
Natasha Gormley, Phone: 9025-473-8387, Email: natashe.gormley@cdha.nshealth.ca
Trudy Campbell, Phone: 902-473-7947, Email: trudy.campbell@cdha.nshealth.ca
Virender Bhan, Principal Investigator

MS Clinic, Kingston General Hospital, Kingston, Ontario K7L 2V7, Canada; Terminated

MS Clinic, London Health Sciences Centre, London, Ontario N6A 5A5, Canada; Recruiting
Anne Howley, Phone: 519-685-8500, Ext: 35352, Email: anne.howley@lhsc.on.ca
Marcelo Krememchutzky, Principal Investigator

The Ottawa Hospital, Multiple Sclerosis Research Clinic, Ottawa, Ontario K1H 8L6, Canada; Recruiting
Carol Freedman, Phone: 613-737-8104, Ext: 2, Email: cfreedman@ottawahospital.on.ca
Dawn Carle, Phone: 613-737-8104, Ext: 2, Email: dcarle@ottawahospital.on.ca
Mark Freedman, Principal Investigator

Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5, Canada; Recruiting
Kathleen Carr, Phone: 416-480-4970, Email: Kathleen.Carr@sunnybrook.ca
Liesly Lee, MD, Principal Investigator

Clinique Neuro Rive-Sud, Greenfield Park, Quebec J4V2J2, Canada; Recruiting
Julie Lafreniere, Phone: 450-672-5221, Email: jl.nrs@videotron.ca
Christine Guerette, Phone: 450-672-5221, Email: cg.nrs@videotron.ca
Francois Grand'Maison, Principal Investigator

CHUM Notre-Dame, Montreal, Quebec H2L 4M1, Canada; Recruiting
Melanie Bosse, Phone: 514-890-8000, Ext: 25968, Email: melanie.bosse.chum@ssss.gouv.qc.ca
Renee Dubois, Phone: 514-890-8000, Ext: 25173, Email: renee.dubois.chum@ssss.gouv.qc.ca
Pierre Duquette, Principal Investigator

CHAUQ Enfant-Jesus, Quebec City, Quebec G1J 1Z4, Canada; Recruiting
Lucie Morel, Phone: 418-649-0252, Ext: 3559, Email: lucie.morel.cha@ssss.gouv.qc.ca
Stephanie Gormley, Phone: 418-649-0252, Ext: 3530, Email: stephanie.gormley.cha@ssss.gouv.qc.ca
Manon Thibault, Principal Investigator

Starting date: January 2009
Last updated: March 21, 2012