| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Relapsing Multiple Sclerosis |
|
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
To determine the effect of RO0506997 on MS by assessing the number of new
gadolinium-enhancing lesions developing while on treatment (specifically the sum of
new lesions seen on the weeks 4, 8 and 12 MRIs). |
|
| E.2.2 | Secondary objectives of the trial |
| Effect on other MRI lesions, MS clinical status and safety. |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
| Exploratory sub-study in a selected set of centers to measure certain cell surface antigens by means of fluorescence activating cell sorting (FACS). |
|
| E.3 | Principal 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
i) If female: Postmenopausal (i.e. spontaneous amenorrhea for the past yearconfirmed by an FSH level greater than 40 mIU/mL unless the patient is
receiving HRT1), surgically sterile (i.e. tubal ligation, hysterectomy), or if of childbearing potential, must use abstinence or two methods of contraception throughout the trial. These should include one primary (e.g. systemic hormonal contraception, vasectomy of the male partner) AND one secondary barrier method (e.g. latex condoms, spermicide) OR a double barrier method (e.g. latex condom plus spermicide (e.g. foam, suppository, gel, cream)) may be used.
(1)Definition of postmenopausal for patients participating in the study at sites in
Germany: spontaneous amenorrhea for 2 years, FSH levels > 40 mIU/mL and
estrogen levels < 30 pg/ml (unless the patient is receiving HRT and is over 55
years of age).
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. |
|
| E.4 | Principal 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 treat symptoms of spasticity, depression and
fatigue:
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: 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: natalizumab, 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 over-the-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 with a live vaccine. 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 using, for example, DSM-IV criteria for substance abuse
5) History of HIV or Hepatitis C Infection, Tuberculosis (TB), 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 or renal impairment which would contraindicate gadolinium injection
9) Current or history of cancer, excluding localized non-melanoma skin cancer
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 assessment of MS
3) ECG QTcF interval > 450 msec
4) A positive pregnancy test
5) Positive JCV DNA, HIV, Hepatitis B (HBsAg) or Hepatitis C (HepCAb) screening tests
6) Positive PPD (Mantoux) (≥ 10 mm induration, or according to national (standards) unless there is a history of BCG immunization and the investigator ascertains that there is no recent history of TB exposure; OR positive QuantiFERON-TB Gold test
7) Findings consistent with active or latent TB based on chest radiography performed within 12 months of screen
The following 5 items refer only to the last assessment before baseline. So for example if the screening result would have excluded proceeding to baseline the test may be repeated and the patient may be entered as long as the last value before baseline was acceptable.
8) Hemoglobin:
females: < 10 g/dL (< 6.2 mmol/L)
males: < 11 g/dL (< 6.8 mmol/L)
9) Leukocyte count < 3,000 /mm3 (< 3 x 10 exp9/L)
10) Lymphocyte count < 1,000/mm3 (< 1 x 10 exp9/L)
11) Platelet count < 100,000 /mm3 (< 100 x 10 exp9/L)
12) Urea nitrogen, total bilirubin, ALT or AST ≥ 2.5 times the upper limit of normal |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary endpoint is the cumulative number of MRI enhancing lesions. Other
endpoints are the cumulative number of active MRI lesions and the proportion of active MRIs. Clinical endpoints are the rate of MS attacks and change of MS status on the EDSS scale. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 32 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| The end of the trial is defined as the last visit of the last subject taking part in the trial. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 5 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
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