E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Rheumatoid Arthritis, a disease characterized amongst others by tender and swollen joints |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10042952 |
E.1.2 | Term | Systemic rheumatoid arthritis |
E.1.2 | System Organ Class | 100000004859 |
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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 |
The primary objective of the study is to evaluate the effect of drug delivery method (prefilled syringe or auto-injector) on the PK of tabalumab after the administration of the loading dose in patients with RA who have had an inadequate response to methotrexate (MTX) |
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E.2.2 | Secondary objectives of the trial |
• Evaluate the effect of body weight and the site of injection (arm, thigh, or abdomen) on the PK over 12 weeks
• To summarize the effect of tabalumab SC administration via prefilled syringe or auto-injector on the following outcomes over 12 weeks: ACR 20%, ACR 50%, ACR 70% and ACR-N; DAS28 and DAS28-CRP; EULAR-28 and individual component of ACR.
• To evaluate the frequency of development of anti-tabalumab antibodies over 12 weeks in patients administered tabalumab SC via prefilled syringe or auto-injector
• To evaluate the frequency of operation failures over 12 weeks in patients administered tabalumab via prefilled syringe or auto-injector
• To evaluate ease of use and confidence of tabalumab SC administrations via auto-injector using the Subcutaneous Administration Assessment Questionnaire (SQAAQ) at Weeks 0, 4, and 8
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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 |
Title: Protocol Addendum H9B-MC-BCEF(1) Pharmacokinetic Evaluations of Tabalumab Following Subcutaneous Administration by Prefilled Syringe or Auto Injector in Patients with Rheumatoid Arthritis Who Have Had an Inadequate Response to Methotrexate
Scope: US only
Objectives: To evaluate the auto-injector duration of injection
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E.3 | Principal inclusion criteria |
• Patients ≥18 years of age with diagnosis of adult-onset RA as defined by the 2010 RA classification and diagnosis of disease for at least 6 months prior to screening.
• At least 8 tender and swollen joints.
• Adnormal C-Reactive Protein (CRP) level or Erythrocyte Sedimentation rate (ESR) rate.
• Positive for Rheumatoid Factor (RF) and/or Anti-cyclic citrullinated peptide antibody (anti-CCP Ab).
• Regular use of MTX for at least 12 weeks and stable dose (10 to 25 mg/week) for at least 8 weeks prior to baseline.
• ACR functional class I, II, or III.
• Able and willing to inject study drug by themselves (or have an assistant who will inject study drug) and able and willing to complete all study procedures.
• Able and willing to have blood drawn for PK sampling per protocol (PP).
• Female patients of childbearing potential must test negative for pregnancy at the time of enrollment and agree to use 2 reliable methods of birth control or remain abstinent during the study or for at least 8 weeks following the last dose of study drug, whichever is longer, or, must be a female of non-childbearing potential.
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E.4 | Principal exclusion criteria |
• Use of oral corticosteroids at average daily doses of >10 mg/day of prednisone or its equivalent within 6 weeks prior to baseline. Injection of any parenteral (including intra-articular) corticosteroid within 6 weeks of baseline.
• Have previously discontinued treatment with a DMARD or a novel drug that interrupts cytokine signaling (eg, JAK inhibitors) due to insufficient efficacy.
• Previous severe reaction to any biologic therapy.
• Have had an inadequate response to treatment with 3 or more of the following DMARDs prescribed alone or in combination at approved doses for a minimum of 90 days: leflunomide, azathioprine, cyclosporine, and/or sulfasalazine.
• Use of other DMARDs other than MTX, hydroxychloroquine, chloroquine, or sulfasalazine, in the 8 weeks prior to baseline.
• Any previous treatment with alkylating agents such as cyclophosphamide or chlorambucil.
• Surgical treatment within 60 days prior to baseline of a joint that is to be assessed in the study or will require such treatment during the study.
• Any major surgery within 60 days prior to baseline or required during the study.
• Active fibromyalgia or diagnosis of any systemic inflammatory condition other than RA. Patients with secondary Sjögren's syndrome are not excluded.
• Any malignancy within the past 5 years, except for cervical carcinoma in situ, that has been resected with no evidence of recurrence or metastatic disease or basal cell or squamous epithelial skin cancers that were completely resected and have no evidence of recurrence for at least 3 years.
• Presence of significant uncontrolled cerebro-cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic or neuropsychiatric disorders, or abnormal laboratory values at screening
• ECG abnormalities that are considered clinically significant
• Live vaccine within 12 weeks prior to baseline or intend to receive a live vaccine during the course of the study.
• Evidence of or positive test for hepatitis B (positive for hepatitis B surface antigen [HBsAg+]) OR are positive for hepatitis B core antibody (HBcAb+) and negative for hepatitis B surface antibody(HBsAb-) at screening.
• Hepatitis C virus (HCV; positive for anti–hepatitis C antibody with confirmed presence of HCV.)
• Positive for human immunodeficiency virus (HIV; positive for human HIV antibodies).
• Serious infection (for example, pneumonia or cellulitis) within 3 months of baseline or had serious bone or joint infections within 6 months of baseline or are immunocompromised to an extent such that participation in the study would pose an unacceptable risk to the patient.
• An active or recent infection (including symptomatic herpes zoster or herpes simplex) within 30 days of screening (Visit 1) or between Visit 1 and Visit 2.
• Evidence of active or latent TB as documented by a PPD test with an induration ≥5 mm between 2 and 3 days after application (regardless of vaccination history, medical history, and chest X‑ray at screening). In locations where the QuantiFERON®-TB Gold test is available, it may be used instead of the PPD test.
• Known hypogammaglobulinemia or a screening serum immunoglobulin G (IgG), immunoglobulin M (IgM), or immunoglobulin A (IgA) concentration less than the lower limit of normal.
• Significant hematological abnormalities, including hemoglobin <8.5 g/dL, total platelet count <100,000 cells/µL, total white blood cell (WBC) count <3000 cells/µL, neutrophil count <2000 cells/µL, or lymphocyte count <1000 cells/µL.
• Any other condition that renders the patient unable to understand the nature, scope, and possible consequences of the study or precludes the patient from following and completing the protocol, in the opinion of the Investigator.
• Blood donation of >500 mL within the 30 days before screening or intention to donate blood during the course of the study.
• Women who are pregnant, lactating, or breastfeeding.
• Have previously received tabalumab in this or any other study.
• Are Investigator site personnel directly affiliated with this study and/or their immediate families. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.
• Employees of Lilly or of third-party organizations (TPOs) involved in the study who require exclusion of their employees.
• Currently enrolled in, or have discontinued within the last 30 days or within 5 half‑lives (whichever is longer) from, a clinical trial involving an investigational drug or device or off-label use of a drug or device, or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
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E.5 End points |
E.5.1 | Primary end point(s) |
to evaluate the effect of delivery system (Auto-Injector or Prefilled Syrine) over Cmax and AUC(0-14days) following the first dose of 180 mg |
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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 effect of injection site and body weight over Cmax and AUC(0-14days) following the first dose of 180 mg |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
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 | 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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 15 |
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 |
Czech Republic |
Poland |
Russian Federation |
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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End of study is the date of the last visit or last scheduled procedure for the last active subject in 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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |