E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Immunoglobulin A (IgA) nephropathy |
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E.1.1.1 | Medical condition in easily understood language |
IgA nephropathy (IgAN) is a kidney disease that occurs when an antibody called immunoglobulin A (IgA) lodges in the filters of the kidneys, causing progressive kidney damage. |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10021263 |
E.1.2 | Term | IgA nephropathy |
E.1.2 | System Organ Class | 10038359 - Renal and urinary 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 evaluate whether treatment with belimumab for 12 months can modulate proteinuria in patients with IgA nephropathy. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate whether treatment with belimumab for 12 months can modulate autoantigen and antibody production in IgA nephropathy. • To evaluate the safety and tolerability of 12 months treatment with belimumab in IgA nephropathy. • To evaluate the effect of belimumab compared to placebo on renal function in IgA nephropathy. • To evaluate the effect of 12 months treatment with belimumab on pharmacodynamic (PD) markers and other markers of autoimmunity and their relationship with clinical measures in IgA nephropathy. • To evaluate the effect of 12 months treatment with belimumab on quality of life in IgA nephropathy. • To evaluate the sustainability of any change in proteinuria, PD markers and quality of life in the 12 months following treatment with belimumab. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Subjects with IgAN, aged between 18-75 years • Biopsy proven IgAN, with an IgAN Oxford Classification Score of M1 and/or E1 and T0/1 • Clinically active disease, defined by proteinuria ≥ 0.5 g/24h (PCR ≥ 50 mg/mmol) on two separate occasions despite at least 3 months of maximized supportive therapy • Female subjects not of child bearing potential, or of child bearing potential agreeing to use one of the contraceptive methods listed in the protocol
Other protocol defined inclusion criteria may apply. |
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E.4 | Principal exclusion criteria |
• Secondary cause of IgAN, or renal impairment due to a condition that is not IgAN • Severely reduced or deteriorating kidney function, defined by an eGFR < 30 ml/min at screening, or >15% decrease in eGFR in 3 months before screening • Nephrotic syndrome • Uncontrolled hypertension (>150/90 mmHg) • Concomitant or recent immunosuppression • Participation in another clinical trial of an investigational medicinal product (a minimum period of 1 year will be allowed between study completion of a biological investigational agent and commencement of this study, or 2 months for a non-biologic investigational agent) • Use of traditional herbal medicines • Prior use of biologic and/or cytotoxic therapies, and/or live vaccines within specified time periods • Major organ transplant • Malignant neoplasm within last 5 years • Acute, chronic or recurrent infection • Liver disease or abnormal liver function tests • Significant unstable or uncontrolled co-morbid conditions • Positive serology (HIV, Hepatitis B or C) • History of primary immunodeficiency • Significant IgG deficiency • IgA deficiency • Laboratory test abnormalities • Drug sensitivity/anaphylaxis • Drug or alcohol abuse or dependence • Blood donation during the study period • Serious suicide risk or suicidal ideation
Other protocol defined exclusion criteria may apply. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Percent change from baseline in proteinuria at Week 52 |
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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) |
• Change from baseline in proteinuria levels • Change from baseline in autoantigen and antibody production • Safety and tolerability, as assessed by evaluation of adverse events (AE), clinical laboratory assessments (clinical chemistry, haematology, urinalysis), and vital signs • Change from baseline in renal function (serum creatinine, eGFR) • Change from baseline in pharmacodynamic/biomarker endpoints, which may include B and T cell populations, cytokines/chemokines, autoantibody profile, as data permit • Change from baseline in SF-36 v2 Quality of Life (QoL) questionnaire score |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Weeks 52 and 104 depending on endpoint |
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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) | 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.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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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 | 1 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 1 |