| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| RHEUMATOID ARTHRITIS (RA) |
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| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| 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 |
| The objectives of this study are to assess the efficacy of CRx-102 in subjects with active RA using ACR 20 and to assess the safety and tolerability of CRx-102. |
|
| E.2.2 | Secondary objectives of the trial |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
To be eligible to participate in the study, subjects must meet the following criteria at the time of Screening:
· I01 Subject must voluntarily give written informed consent
· I02 Subject must be ≥ 18 years of age
· I03 Subject must have RA (ACR criteria)
· I04 Subject must have at least 4 swollen joints and at least 6 tender joints at screening and baseline (28 joint count)
· I05 Subject must have a C-Reactive Protein > Upper Limit of Normal at screening
· I06 Subject must have been on DMARD or DMARD combination (e.g. MTX + hydroxychloroquine) for at least 3 months and be on a stable dose of DMARD(s) for at least 6 weeks prior to screening.
· I07 For MTX subjects: MTX ≥ 7.5 mg weekly (po/sc/im) and willing to take folic acid or follinic acid supplementation
· I08 Subject willing to take concomitant multivitamin or ≥ 400 I.U. vitamin D and ≥ 1000 mg of elemental calcium daily
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| E.4 | Principal exclusion criteria |
Subjects will be excluded from study entry if any of the following criteria exist at the time of Screening:
Medical History:
· E01 History of clinically significant (as determined by the Investigator) cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other major disease
· E02 Wheelchair or bed bound
· E03 History of osteoporotic fracture
· E04 History of malignancy within the past 10 years. However, subjects with a history of treated or excised basal cell carcinoma or fewer than 3 squamous cell carcinomas are eligible to participate
· E05 History of lymphoma or chronic leukemia
· E06 Moles or lesions that are currently undiagnosed, but are suspicious for malignancy
· E07 Surgery within the previous 3 months (except for minor dental and cosmetic)
· E08 History of drug or alcohol abuse (as defined by the Investigator)
· E09 History of bleeding disorder
· E10 History of gastrointestinal bleeding within 5 years of screening
· E11 History of severe migraines or headaches
· E12 History of glaucoma
· E13 Active diabetic retinopathy
· E14 Visually compromising cataract
Infection History:
· E15 History of opportunistic infection within the previous 12 months
· E16 Active Tuberculosis
· E17 Serious local infection (e.g., cellulitis, abscess) or systemic infection (e.g., septicemia) within 3 months prior to screening
· E18 Fever or symptomatic viral or bacterial infection within 2 weeks prior to screening
· E19 Positive for hepatitis C (HCV) antibody
· E20 Positive for hepatitis B surface antigen (HBsAg)
· E21 Known positive HIV antibody
Treatment History:
· E22 Has a history of hypersensitivity to glucocorticoids and/or dipyridamole
· E23 Treatment with oral, intra-articular, intramuscular, or intravenous glucocorticoids within 6 weeks prior to screening; inhaled glucocorticoid is permitted
· E24 Treatment with any TNFα biologic, anakinra or abatacept within 2 months prior to screening
· E25 Treatment with rituximab
· E26 Treatment with another investigational drug, investigational device or approved therapy for investigational use within 3 months prior to screening
· E27 Treatment with anticoagulants including: dipyridamole, warfarin, clopidogrel, ticlopidine
o Acetylsalicylic acid > 150 mg per day
· E28 Treatment with any concomitant medications that have not been at a stable dose for at least 28 days prior to screening
Laboratory Exclusions:
· E29 ALT or AST laboratory values that exceed 1.5 x ULN
· E30 HgbA1C value of > 7.0%
Miscellaneous:
· E31 Current enrollment in any other study with investigational drug or device
· E32 Female subject who is pregnant or lactating or of child bearing potential and not using acceptable methods of contraception (birth control pills, barriers or abstinence)
· E33 Unwilling or unable to comply with the requirements of this protocol, including the presence of any condition (physical, mental, or social) that is likely to affect the subject’s return for follow-up visits on schedule
· E34 Other unspecified reasons that, in the opinion of the Investigator or sponsor make the subject unsuitable for enrollment
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| E.5 End points |
| E.5.1 | Primary end point(s) |
Primary Endpoint:
To assess the superiority of CRx-102 (2.7 mg/360 mg) compared to prednisolone (2.7 mg) and dipyridamole (360 mg) using ACR 20 calculated from Baseline to Day 98 in subjects with active RA
Secondary endpoints:
To assess the efficacy of CRx-102 (2.7 mg/180 mg) compared to prednisolone (2.7 mg) and dipyridamole (360 mg) using ACR 20 calculated from Baseline to Day 98
To assess the efficacy of each dosage of CRx-102 to placebo using ACR 20 calculated from Baseline to Day 98
Exploratrory endpoints:
To assess the efficacy of each dosage of CRx-102 compared to prednisolone (2.7 mg), dipyridamole (360 mg), and placebo using DAS 28
To assess the efficacy of each dosage of CRx-102 compared to prednisolone (2.7 mg), dipyridamole (360 mg), and placebo in lowering CRP levels
Hand x-ray analysis will be performed to assess potential disease modifying activity including joint space narrowing, erosions and total Sharp score. |
|
| 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 | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| 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) | Yes |
| 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 | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 51 |
| 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
| |
| 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 | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| 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 | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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