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 |
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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 assess the safety and efficacy of different dose regimens of ILV-094 compared with placebo, administered subcutaneously to subjects with active Rheumatoid Arthritis on a background of methotrexate. |
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E.2.2 | Secondary objectives of the trial |
To assess the pharmacokinetic (PK), pharmacodynamic (PD), immunogenicity profile and subject-reported outcomes. |
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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 |
Optional Pharmacogenetic sub-study: Genotypes from whole blood samples may be measured and analyzed for markers associated with rheumatoid arthritis and response to ILV-094 administration. Optional Pharmacogenomic sub-study: RNA from whole blood samples collected during the study may be measured and analyzed for markers associated with rheumatoid arthritis and response to ILV-094 administration. |
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E.3 | Principal inclusion criteria |
1. Male or female aged 18 years or older at the time of signing the ICF (or older as required by local regulation or ethics committees). 2. All male and female subjects who are biologically capable of having children must agree and commit to the use of a highly effective method of birth control for the duration of the study and for 12 weeks after the last dose of test article. A subject is still biologically capable of having children if he or she is using contraceptives or if his or her sexual partner is sterile or using contraceptives. 3. Meets the American College of Rheumatology (ACR) 1987 revised criteria for classification of RA for at least 6 months prior to screening. 4. ACR functional class I through III. 5. Active RA at the time of screening and baseline consisting of ≥ 5 swollen and ≥ 5 tender joints (28-joint count) and at least 1 of the following at screening: a. C-reactive protein (CRP) ≥ 10 mg /L. b. Erythrocyte sedimentation rate (ESR) (as measured by the Westergren method) ≥ 28 mm/h. 6. Must be receiving methotrexate for at least 12 weeks, with stable route and dose (up to 25 mg weekly according to standard medical practice and local regulation) for at least 8 weeks prior to the expected baseline visit. 7. Negative urine pregnancy test result for all women.
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E.4 | Principal exclusion criteria |
1. Any major illness/condition or evidence of unstable clinical condition (eg, cardiovascular, cerebrovascular, neurologic, metabolic, immunologic, infectious, hepatic, or renal condition; uncontrolled diabetes mellitus; or hypertension) or any serious disorder (eg, current or history of alcohol or drug abuse, current or history of psychiatric disease) that, in the investigator’s judgment, will substantially increase the risk associated with the subject’s participation in and completion of the study, or could preclude the evaluation of the subject’s response, or interfere with the subject’s ability to give informed consent. 2. Pregnant or breastfeeding women or women planning to become pregnant during the study. A urine pregnancy test must be performed during the screening and baseline visits for all women. 3. Subjects with other rheumatic diseases, including but not limited to Lyme disease, psoriatic arthritis, spondyloarthropathy, systemic lupus erythematosus, systemic vasculitis, polymyositis, infectious or reactive arthritis, overlap syndrome, scleroderma, Reiter syndrome, or primary Sjögren syndrome. 4. Cancer or history of cancer (other than adequately treated cutaneous basal cell carcinoma and squamous cell carcinoma of the skin or in situ cervical cancer, with no evidence of recurrence). 5. Contraindications for treatment with methotrexate. 6. Positive for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HBsAg), and/or hepatitis C antibodies (HCV). 7. History of drug-induced liver injury, liver cirrhosis, or fibrosis at any time before the baseline visit. 8. Laboratory abnormalities at screening including the following: a. Hemoglobin < 8.5 g/dL (SI units: < 85 g/L) b. White blood cell (WBC) count < 3.3 x 103/mm3 (SI units: < 3.3 x 109/L) c. Platelets < 110,000/mm3 or ≥ 1,000,000/mm3 (SI units: < 110 x 109/L or ≥ 1,000 x 109/L) d. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 1.5 x the upper limit of normal (ULN) e. Serum creatinine > 2 mg/dL (SI units: > 177 μmol/L) 9. Other clinically significant laboratory, electrocardiogram (ECG), or vital sign abnormalities at screening. 10. Active tuberculosis or history of active tuberculosis. Subjects with latent tuberculosis are allowed if there is documentation of completion of a course of chemoprophylaxis per country-specific medical guidelines. A tuberculosis test, interpreted by the investigator according to local standards or country specific-guidelines, must be performed during the screening visit for subjects with no documentation of tuberculosis test results available within 4 weeks before the baseline visit. 11. Clinically significant finding on chest radiograph within 3 months before the baseline visit. A chest X ray must be obtained during the screening visit for subjects with no documentation of chest X ray results available within 3 months before baseline. 12. Known or suspected allergy or intolerance to any components of test article (refer to the investigator’s brochure), or other compounds related to these classes of medication. 13. Known hypersensitivity reaction to medicine, including biopharmaceutical proteins. 14. Any prior use of B cell-depleting therapy. 15. Receipt within 24 weeks before the baseline visit: • any investigational biological drugs not listed under the other exclusion criteria • any cytotoxic agents, including cyclophosphamide (cytoxan), or chlorambucil • intravenous immunoglobulin (IVIG) • Prosorba column (extracorporeal immunoadsorption protein A column) 16. Receipt within 12 weeks before the baseline visit: • any investigational drugs (other than investigational biological drugs and those not listed under the other exclusion criteria) or devices • any disease-modifying antirheumatic drugs (DMARDs) (including biological drugs), other than methotrexate, or immunosuppressive drugs not listed under the other exclusion criteria. • any surgical joint interventions (open or arthroscopic) 17. Receipt within 8 weeks before the baseline visit: • abatacept, adalimumab, or infliximab 18. Receipt within 4 weeks before the baseline visit: • etanercept, hydroxychloroquine, or sulfasalazine • intra-articular hyaluronic acid injections • any live (attenuated) vaccine • change in the dose of folic or folinic acid 19. Receipt within 2 weeks before the baseline visit: • more than 10 mg/day of oral prednisone or equivalent, or a change in the dose of prednisone or its equivalent, or having intra-articular corticosteroid injection or bolus intramuscular (IM) or IV treatment with corticosteroids (≥ 20 mg prednisone or equivalent) • more than 1 nonsteroidal anti-inflammatory drug (NSAID), or a change in the dose of the NSAID, or an NSAID dose greater than the maximum recommended dose (Aspirin at doses up to 325 mg for cardiac protection daily is permitted.)
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint will be ACR20 at week 12. |
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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 | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity, subject-reported outcomes |
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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.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 26 |
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 |
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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
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The end of the study is the last visit of the last subject. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 18 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 18 |
E.8.9.2 | In all countries concerned by the trial days | 0 |