E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of patients with moderate to severe rheumatoid arthritis (RA) |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10039075 |
E.1.2 | Term | Rheumatoid arthritis and associated conditions |
E.1.2 | System Organ Class | 10021428 - Immune system disorders |
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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 determine the safety of Z102 relative to standard glucocorticoid comparators (5.0 mg and 7.5 mg prednisone) over a 12-month period in patients with Rheumatoid Arthritis (RA) using the following assessment tools:
o Adverse events
o Vital signs
o Clinical laboratory and clinical chemistry evaluations
o Physical examination and body weight
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of Z102 relative to standard glucocorticoid comparators (5.0 mg and 7.5 mg prednisone) over a 12-month period in patients with Rheumatoid Arthritis (RA) using the following assessment tools:
o Joint imaging and bone density using plain radiography and dual-energy X-ray absorptiometry (DXA)
o Disease Activity Scor 28 (DAS28)-CRP and individual components
o American College of Rheumatology (ACR) 20, ACR 50, and ACR 70
o Multidimensional Assessment of Fatigue (MAF)
o Time to failure
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Prior to Screening, have voluntarily signed the Informed Consent Form. Completing patients from Protocol Z102-008 will sign informed consent for Protocol Z102-009 prior to their termination visit in Protocol Z102-008.
2. Have completed all 12 weeks of Protocol Z102-008 or discontinued after participating in at least 6 weeks of the randomized withdrawal portion of Z102-008 for acceptable reasons (i.e., for reasons other than AE, protocol violation, or non-compliance). If Protocol Z102-008 participation terminated early, the full 12-week period (inclusive of study participation period) must elapse before participants in Z102-008 may be considered for participation in the 52-week extension study (Z102-009).
3. Have met all inclusion/exclusion criteria for enrollment into Protocol Z102-008.
4. Have been on DMARD therapy for at least 90 days and have been on a stable DMARD dose without dosage adjustment or modification for 6 weeks prior to enrollment into Protocol Z102-008, and be able to maintain the same dose of conventional DMARD therapy during Protocol Z102-009 participation (with or without glucocorticoid therapy); stable DMARD therapy may include a combination of DMARD agents (methotrexate and azulfidine or methotrexate and hydroxychloroquine as examples).
5. At Screening, female patients of childbearing potential (18 to 55 years of age, inclusive) must have negative urinary beta human chorionic gonadotropin (beta hCG) tests.
6. Female patients of childbearing potential (18 to 55 years of age, inclusive) must use acceptable methods of birth control (including, but not limited to, intrauterine device [IUD], oral or injectable contraceptives, barrier methods, or abstinence) for the duration of Protocol Z102-009.
7. If currently taking the following medications, she/he has been on a stable dose of the same drug for at least 3 months prior to entering into Protocol Z102-008, continued on the same dose during Protocol Z102-008, and should be able to continue on the same dose for the duration of Protocol Z102-009: statins, diuretics, thyroid hormone, hypoglycemic medications, and cardiovascular medications.
8. Have no general or specific changes in his/her condition unacceptable for further treatment in the judgment of the investigator. |
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E.4 | Principal exclusion criteria |
1. Did not complete 6 weeks of the double-blind section of Protocol Z102-008, or was discontinued from Protocol Z102-008 for reasons of an AE, protocol violation, or non-compliance.
2. Female patient who is pregnant or lactating or of childbearing potential not using acceptable methods of birth control (including, but not limited to, IUD, oral or injectable contraceptives, barrier methods, or abstinence).
3. Patients who do not respond to therapies that include a dose less than 10 mg prednisone and either a DMARD combination, DMARD/biologic combination, or biologics alone.
4. Active cardiovascular disease, unless well controlled by appropriate treatment, for a minimum of 3 months prior to screening for enrollment into Protocol Z102-008.
5. Currently taking aspirin for reasons other than for cardiovascular prophylaxis or their total daily dose is greater than 325 mg.
6. Taking oral steroids at a daily prednisone dose, or the equivalent, of >10 mg/day within the past 2 weeks.
7. Intraarticular, intramuscular, or intravenous glucocorticoids must not have been given at least 6 weeks prior to entering study Protocol Z102-008 or Protocol Z102-009, at any time during the study, or be anticipated to be given at any time during the study.
8. The need to continue the use of one or multiple NSAIDs at the same time, or use acetaminophen on a chronic basis. Acetaminophen/paracetamol is permitted episodically for pain during the titration and stable dose treatment period for Protocol Z102-009, not exceeding 1.5 g/day for any 3 days in any 7-day interval. There are no exclusions during the 30-day follow-up period.
9. All opiate use is prohibited. Such agents include oxycodone, hydrocodone, codeine, morphine sulfate, Demerol (meperidine/pethidine), Dilaudid (hydromorphone), tramadol, combination products including Percocet (oxycodone and acetaminophen), Hydrocet (dihydrocodeine and acetaminophen), Tylenol (acetaminophen or paracetamol) with codeine, Vicodin (hydrocodone and acetaminophen), Lorcet (hydrocodone and acetaminophen), Lortabs (hydrocodone and acetaminophen) extended-release formulations.
10. Use of any other medications or herbs or non-pharmacological treatments (e.g., acupuncture) used for the treatment of pain is prohibited.
11. Excluded medications include systemic anticoagulants, including dipyridamole, Coumadin (warfarin), clopidogrel, ticlopidine, and aspirin exceeding 325 mg/day (whether or not taken for cardiovascular prophylaxis). All systemic antifungal agents are excluded, including (but not limited to) the polyene macrolides (amphotericin B), the azoles (ketoconazole, miconazole, itraconazole, and fluconazole), and the allylamines (terbinafine). All anti-HIV drugs belonging to the following classes are prohibited: members of the nucleoside/nucleotide reverse transcriptase inhibitors, non-nucleoside/nucleotide reverse transcriptase inhibitors, protease inhibitors, fusion and entry inhibitors, and integrin inhibitors. These agents include (but are not limited to) abacavir, zidovudine, didanosine, tenofovir, and efavirenz.
12. Has, or has had any active severe infections, such as osteomyelitis, sepsis, active infectious hepatitis, endocarditis, systemic fungal infection, or recent invasive surgical procedures within 30 days of Protocol Z102-008 or Protocol Z102-009 initiation.
13. Known HIV, hepatitis B, or hepatitis C infection.
14. Has undergone administration of any investigational drug within 30 days of study Protocol Z102-008 initiation, and within 30 days of Protocol Z102-009 initiation, other than Protocol Z102-008, or intends to participate in any investigational drug trial during the study.
15. All biologic agents are excluded for 90 days prior to Screening and during the conduct of Protocol Z102-008, and Protocol Z102-009.
16. Has undergone administration of rituximab or any B-cell depleting investigational drugs within 6 months of Protocol Z102-008 Screening or Protocol Z102-009 initiation, or at any time during participation in study Protocol Z102-008, and throughout the conduct of Protocol Z102-009.
17. Has a history of hypersensitivity reaction to glucocorticoids and/or dipyridamole.
18. Known or suspected history of alcohol or drug abuse within 2 years prior to Screening for Protocol Z102-008.
19. Has any other medical condition which may interfere with the conduct of this study in the opinion of the investigator.
20. Has limited mental capacity or language skills such that simple instructions cannot be followed or information regarding AEs cannot be provided. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To determine the safety of Z102 relative to standard glucocorticoid comparators (5.0mg and 7.5mg prednisone) over a 12 month period in patients with Rheumatoid Arthritis (RA). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
To evaluate the efficacy of Z102 relative to standard glucocorticoid comparators (5.0mg and 7.5mg prednisone) over a 12 month period in patients with Rheumatoid Arthritis (RA). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 14 |
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 | No |
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 |
Argentina |
Brazil |
Bulgaria |
Canada |
Chile |
Hungary |
Mexico |
Peru |
Poland |
Russian Federation |
Serbia |
Ukraine |
United States |
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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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Following the last patient-last dose, the completion of the 2 week follow-up of this patient represents the end of trial. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 15 |
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 | 11 |
E.8.9.2 | In all countries concerned by the trial days | 15 |