Phase II, multicenter, randomised, double-blind, placebo-controlled, parallel group, dose-ranging study to determine the effect on MRI lesions and safety of RO0506997 in Relapsing Multiple Sclerosis

Phase 1

• Conditions: Relapsing Multiple Sclerosis

• Registration Number: EUCTR2004-004519-43-SK
• Lead Sponsor: F. Hoffmann-La Roche Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-02-13
• Last Update Posted: 20 February 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

Protocol section 4.1.1: MS-related Inclusion Criteria
1) Diagnosis of relapsing MS types 1-4 based on McDonald criteria” as revised in
2005 (Appendix 1), without taking into account the screening MRI results
2) EDSS score of = 6.5 (Appendix 2)
3) Between 12 months and 1 month previous: 1 or more MS attack (which has been
documented in prior medical records) or a brain MRI with a gadolinium-enhancing
lesion consistent with an MS lesion (based on radiology report or investigator review
of MRI)

Protocol section 4.1.3: Other Inclusion Criteria
1) Signed written informed consent
2) Men or women 18-59 years of age
3) If female: postmenopausal for the past year (confirmed by an FSH level greater
than 25 mIU/mL unless the patient is receiving HRT), or surgically sterile (i.e.
tubal ligation, hysterectomy) or of childbearing potential with a reliable form of
contraceptive protection:
i) Intrauterine device
ii) Systemic hormonal contraception by the female
iii) Spermicide with or without a male or female barrier method
iv) Abstinence

Protoocl section 4.2.1: Inclusion Criteria at Baseline:
1) Screen MRI meets the Paty criteria” of: = 4 T2 lesions or = 3 T2 lesions if at least 1 is periventricular. It is the responsibility of a site investigator to make this
determination.
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
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Protocol section 4.1.2: MS-related Exclusion Criteria
1) MS attack or systemic corticosteroids within 1 month
2) MS treatments which are given to primarily treat symptoms:
a) Within 3 months: if part of an IRB/EC approved trial
b) Otherwise may remain on the regimen if it is unchanged within 1 month and is
unlikely to change before week 16. This includes cannabis-related agents as well
as categories such as over-the-counter, herbal and nutritional supplement.

The following refer to any other agents given to treat MS (approved or unapproved):
3) Within 3 months: interferon beta, glatiramer acetate, or plasmapheresis
4) Within 12 months: natalizumab, intravenous immunoglobulin, cytapheresis,
azathiaprine, cladribine, cyclophosphamide, methotrexate, mitoxantrone,
mycophenolate, pixantrone, sirolimus, tacrolimus or other agents typically used to
prevent transplant rejection or as cancer chemotherapy, excluding hormonal
treatments
5) Ever having received: stem cell or bone marrow transplant, total lymphoid irradiation,
vaccine therapy for MS or monoclonal antibodies whose effects may be longer than 1
year such as alemtuzumab, daclizumab or rituxan (rituximab)
6) Within 3 months: any other agents given for non-symptomatic treatment of MS which
were not included above in items 3-5 such as HMGCoA-reductase inhibitors,
glitazone”-type antidiabetics, 4-aminopyridine or products related to 4-
aminopyridine, antibiotics, hormone treatment, as well as categories such as overthe-
counter, herbal and nutritional supplement. However, if the agent is being taken
primarily to treat another medical condition, then it is allowed as long as the dose is
unchanged within 3 months and is unlikely to change before week 16

Protocol section 4.1.4: Other Exclusion Criteria
1) Women who are pregnant or may breastfeed before week 16
2) Within 1 month: an infection requiring systemic anti-infective treatment or a
vaccination. Exceptions are treatment of an uncomplicated urinary tract infection or
upper respiratory tract infection.
3) Within 3 months: participation in any IRB/EC investigational drug trial or treatment
with anti-TNF or other potentially immune modulating agents not already
mentioned
4) Within 6 months: alcohol abuse or drug abuse as assessed by the investigator
5) History of HIV infection or progressive multifocal leukoencephalopathy (PML)
6) History of hereditary or acquired immunodeficiency, except for that caused by
pharmaceutical intervention; or currently present hereditary or acquired
immunodeficiency, including that caused by pharmaceutical intervention
7) A medical or neurological condition a) that may significantly interfere with the
absorption of an oral medication, b) which is likely to require a new medication or
hospitalization over the next 6 months or c) that may interfere with the assessment
of MS
8) Presence of pacemakers or foreign metal objects in the eyes, skin, or body which
would contraindicate an MRI scan

Protocol section 4.2.2: Exclusion Criteria at Baseline
1) Since screening, except for the use of systemic corticosteroids for an MS attack (see section 5), use of any new treatment which has been approved for or is being
evaluated for an effect on MS
2) Since screening, development or worsening of a medical or neurological condition
which a) may significantly interfere with the absorption of an oral medication, b) is
likely to require a new medication or hospitalization over the next 6 months, or c)
may interfere with the a

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the effect of RO0506997 on MS by assessing the number of new<br>gadolinium-enhancing lesions developing while on treatment (specifically the sum of<br>new lesions seen on the weeks 4, 8 and 12 MRIs).;Secondary Objective: Effect on other MRI lesions, MS clinical status and safety.;Primary end point(s): The primary efficacy endpoint is the cumulative number of new gadolinium-enhancing<br>MRI lesions recorded during the double-blind treatment period.