| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 8.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10039073 |
| E.1.2 | Term | Rheumatoid arthritis |
|
| 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 evaluate the efficacy of Rob 803 administered orally once daily for 12 weeks in combination with a stable dose of methotrexate in patients with moderate or severe active RA. Efficacy will be evaluated by ACR20 (66 joints count) after 12 weeks of treatment. |
|
| E.2.2 | Secondary objectives of the trial |
•Evaluate the safety of Rob 803 administered orally once daily for 12 weeks in combination with a stable dose of methotrexate in patients with moderate or severe active Rheumatoid Arthritis (RA).
•Evaluate additional efficacy parameters of Rob 803 after 4,8 and 12 weeks of treatment
•Evaluate patient functional disability status (as measured by Modified Health Assessment Questionnaire: mHAQ)
•Evaluate correlation between plasma concentration and effect at week 12.
•Evaluate the pharmacokinetics of Rob 803 when administered orally in combination with a stable dose of methotrexate in a subgroup of 40 patients with moderate or severe active RA.
•Evaluate the pharmacodynamic effect of Rob 803 administered orally in combination with a stable dose of methotrexate. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. ≥ 18 years old
2. Diagnosed with RA based on the ARA 1987 revised criteria
at least 16 weeks prior to study enrolment, Day 0 (Appendix B)
3. Have an ACR global functional status class of 1 to 3
(Appendix C)
4. Have active disease, defined as the presence of 6 swollen
joints and 6 tender joints in a 44 joint examination
5. Have a CRP level at screening of ≥ 1.0mg/dL
6. Have been taking oral or parenteral methotrexate (15 mg
weekly or above), have been using methotrexate for at least
16 weeks (up to Day 0 of study), and have been on a stable dose
for at least 8 weeks, up to Day 0. (Subjects using 10 to 15 mg
methotrexate may be considered for inclusion if an unacceptable
toxicity was recorded when higher doses were used.)
7. Stable optional RA medication:
- Folic acid supplementation if already in use
- Nonsteroidal anti-inflammatory drugs (NSAIDs)
including cyclooxengase-2 (Cox-2) inhibitors – doses
must be stable for 4 weeks prior to dosing with study
drug and consistent with labelling recommendations
- Acetylsalicylic acid is allowed in low doses as
cardiovascular prophylaxis
- Oral glucocorticoids, daily doses of up to 10 mg (incl.) of
prednisolone or equivalent for 4 weeks prior to study
enrolment (Day 0)
- Painkillers (acetaminophen, Tramadol and similar, alone
or in combinations) usage as per routine instructions will
be allowed, except for 24 hours before rheumatology
evaluations
8. Are using adequate forms of birth control - defined as 2
methods of birth control (eg, contraceptive pill and single-barrier
methods). Birth control is not necessary in subjects who have
been postmenopausal for > 1 year or who are surgically sterile
(including hysterectomy)
9. Subjects must be able to give informed consent after reading
and understanding the subject information sheet, are willing to
comply with all study procedures including completing all
questionnaires.
|
|
| E.4 | Principal exclusion criteria |
1. Arthritis onset prior to 16 years old
2. Any of the following infections:
- Known or acute infection that may affect CRP levels
- Active tuberculosis
- Known chronic infection with human immunodeficiency
virus (HIV), hepatitis C virus (HCV) or hepatitis B virus
(HBV) including positive serology
3. Ongoing systemic inflammatory condition which may
interfere with the results of clinical or laboratory tests planned in
the study (eg, systemic lupus erythematosus or any other systemic
rheumatic disease other than RA)
4. Any clinically significant concurrent medical condition
resulting in the following abnormal laboratory values:
- Hepatic
• aspartate aminotransferase (AST) ≥ 2× the upper
limit of normal (ULN)
• alanine aminotransferase (ALT) ≥ 2× ULN
• Alkaline phosphatase ≥ 2.5 × ULN
• Total bilirubin > ULN
- Renal
• Serum creatinine > 1.5 × ULN
• Urea > 1.5 × ULN
• Significant proteinuria (2+ on urinary dipstick test)
- Haematology
• Haemoglobin < 9 g/dL
• Leukocytes < 3.5 × 10exp6/dL
• Absolute neutrophil count (ANC) < 1.5 × 10exp9/L
• Platelets < 100 × 10exp6/L
5. Present or previous malignancies, except cured squamous or
basal skin cell carcinoma
6. Have uncontrolled diabetes mellitus
7. Have any medical condition, which in the judgment of the
Investigator, will put the subject at an unacceptable risk by
participating in the study
8. Require one or several of the following medications:
- Narcotics (except for Tramadol) or any drug for
treatment of RA other than NSAIDs, Cox-2 inhibitors,
acetaminophen/paracetamol for pain and arthritis control,
or aspirin (except for cardiovascular prophylaxis)
- Current or previous use of biological anti-inflammatory or immunemodulatory
therapy for treatment of RA (e.g., anti-IL-1
and anti-B-cell treatment)
- Current or previous use of DMARDs (e.g.
sulphasalazine, antimalarials, etc.), except methotrexate,
within 4 months prior to study enrolment (Day 0)
- Anti-tumour necrosis factor [anti-TNF] 2 months prior to
study enrolment (Day 0)
- Intra-articular, intramuscular, or intravenous
glucocorticoids within 4 weeks prior to study enrolment
(Day 0)
9. Participation in an investigational study within the last 30
days or expects to be treated with an investigational product
during this study period.
10. Current or recent history (within 12 months of screening) of
drug or substance abuse, including alcohol
11. Females who are pregnant or nursing
12. Have any clinically significant abnormality on physical
examination, laboratory testing, vital signs, or 12-lead ECG
suggestive of a significant unstable medical condition
13. Have any other condition that in the opinion of the
Investigator, could interfere with the subject’s study participation.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Efficacy:
ACR 20 improvement measured after 12 weeks; defined as ≥ 20% improvement in tender and swollen joints count and ≥ 20% improvement in at least 3 of the following:
- Subject Disability assessment
- Physician Global assessment
- Subject Global assessment
- Subject pain assessment
- An acute Phase Reactant (C-reactive protein).
|
|
| 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 | Yes |
| 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 | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| 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.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 40 |
| 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 | No |
| 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
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 10 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
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