E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
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 evaluate the safety of long-term exposure with AMG 827 in subjects with rheumatoid arthritis.
To evaluate the efficacy of AMG 827 as measured by the following:
The proportion of subjects achieving an American College of Rheumatology (ACR) 20, 50, and 70 response
Change in Disease Activity Score 28 joint (DAS28) score
The proportion of subjects with DAS28 < 2.6
DAS28 score
ACR individual components |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effect of treatment on patient-reported outcomes, including the Medical Outcomes Short Form-36 (SF-36), Medical Outcomes Study (MOS) Sleep Scale, and Health Assessment Questionnaire Disability Index (HAQ-DI)
To determine the proportion of subjects who develop anti-AMG 827 antibodies
To explore lipid profiles in subjects receiving AMG 827 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subject has provided informed consent.
Subject was randomized into study 20090061 and completed the week 16 evaluation.
For subjects with ≥ 3 months between the week 16 visit of 20090061 and the planned first IP dose in 20090402: Negative test for hepatitis B virus (HBV) surface antigen, hepatitis C virus (HCV) antibody, and/or human immunodeficiency virus (HIV) in subjects if clinically indicated (eg, known recent exposure) in the opinion of the investigator.
For female subjects with ≤ 4 weeks between the week 16 visit of 20090061 and the planned first IP dose in 20090402, a negative urine pregnancy test at baseline prior to the first IP dose in 20090402 (except those at least 3 years post menopausal or surgically sterile).
For female subjects with > 4 weeks between the week 16 visit of 20090061 and the planned first IP dose in 20090402, a negative serum pregnancy test within 28 days prior to initiating IP and a negative urine pregnancy test at baseline prior to the first dose of IP in 20090402 (except those at least 3 years post menopausal or surgically sterile).
For subjects with ≥ 3 months between the week 16 visit of 20090061 and the planned first IP dose in 20090402:
• If the subject entered 20090061 with a negative purified protein derivative (PPD) test: Subject must have a negative PPD test within 30 days prior to the first IP dose. Tuberculin skin tests should be considered positive when they have greater than or equal to 5 mm of induration at 48-72 hours after test is placed.
• If the subject entered 20090061 with a positive PPD and has had a subsequent exposure to tuberculosis: Subject must have a negative Quantiferon test within 30 days prior to the first IP dose. |
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E.4 | Principal exclusion criteria |
Subject had any SAE reported during 20090061 that was considered to be related to IP.
Subject experienced an adverse event in 20090061 that, in the opinion of the investigator, could cause extension of treatment to be detrimental to the subject.
Subject is currently experiencing an infection of CTCAE grade 2 (if requiring oral antibiotics) or higher. Subject is ineligible until the infection is resolved in the opinion of the investigator.
For subjects with > 4 weeks between the week 16 visit of 20090061 and the planned first IP dose in 20090402, subject has laboratory abnormalities at screening, including:
• Elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT); >1.5x upper limit of normal)
• Serum total bilirubin ≥1.5 mg/dL
• Hemoglobin < 11 g/dL
• Platelet count < 125,000 /mm3
• White blood cell count < 3,000 cells/mm3
• Absolute neutrophil count < 2000/mm3
• Estimated creatinine clearance < 50 mL/min (Cockroft-Gault formula, central lab will calculate value and provide to sites)
• Hemoglobin A1c > 8.5 (for type 2 diabetics only)
• Any other laboratory abnormality, which, in the opinion of the investigator, will prevent the subject from completing the study or will interfere with the interpretation of the study results
For subjects with ≥ 3 months between the week 16 visit of 20090061 and the planned first IP dose in 20090402, subject has a serious infection, defined as requiring hospitalization or intravenous antibiotics within 8 weeks before screening.
For subjects with ≥ 3 months between the week 16 visit of 20090061 and the planned first IP dose in 20090402, subject has recurrent or chronic infections, defined as ≥ 3 infections requiring anti-microbials over the past 12 months prior to screening.
Subject has a significant concurrent medical conditions, including:
• Type 1 diabetes
• Poorly controlled type 2 diabetes
• Symptomatic heart failure (New York Heart Association class II, III, or IV)
• Myocardial infarction within the last year
• Current or history of unstable angina pectoris within the last year
• Uncontrolled hypertension as defined by resting blood pressure > 150/90 mmHg prior to first IP dose (confirmed by a repeat assessment)
• Severe chronic pulmonary disease (eg, requiring oxygen therapy)
• Major chronic inflammatory disease or connective tissue disease other than rheumatoid arthritis (eg, systemic lupus erythematosus), with the exception of secondary Sjögren’s syndrome
• Multiple sclerosis or any other demyelinating disease
• Active malignancy, including evidence of cutaneous basal or squamous cell carcinoma or melanoma, or history of cancer (except successfully treated in situ cervical cancer or squamous or basal cell carcinoma of the skin)
• Any condition that, in the opinion of the investigator, might cause this study to be detrimental to the subject
Subject is pregnant or breast feeding, or planning to become pregnant while enrolled in the study, up to the subject’s last study visit including the follow-up period.
Female subject is not willing to abstain from sexual intercourse or use 2 highly effective forms of birth control for the duration of the study and at least 40 days after the last dose (except women at least 3 years postmenopausal or surgically sterile). Highly effective methods of birth control for women include but are not limited to birth control pills, Depo-Provera® injections, contraceptive implants, or occlusive cap (barrier method) in combination with barrier methods used by the man.
Male subject is not willing to abstain from sexual intercourse or use 2 highly effective forms of birth control for the duration of the study, plus an additional 16 weeks after the last dose (except for men who are surgically sterile or whose female partners are at least 3 years postmenopausal or surgically sterile). Highly effective methods of birth control include but are not limited to a condom in combination with hormonal birth control or barrier methods used by the woman.
Male subject (including vasectomised males) with a pregnant female partner is not willing to use effective methods to ensure that an unborn child is not exposed to AMG 827 via semen. Effective methods to ensure that an unborn child is not exposed to AMG 827 via semen include condoms or abstinence. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Adverse events
Change in laboratory parameters (hematology, chemistry and urinalysis profiles) and vital signs
Efficacy endpoints
ACR 20, 50, and 70 at all measured timepoints
DAS28 improvement from baseline at all measured timepoints
DAS28 < 2.6 at all measured timepoints
DAS28 score at all measured timepoints
ACR individual components at all measured timepoints
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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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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
|
The end of the study is defined as the last visit of the last subject off the study. |
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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 | 5 |
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 | 5 |
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 |