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 |
Nephritis caused by deposition of antibodies in the kidneys |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• To evaluate the effect of OMS721 in patients with IgA nephropathy (IgAN) on proteinuria assessed by 24-hour urine protein excretion (UPE) in g/day at 24 weeks from beginning of treatment (BOT) |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effect of OMS721 in patients with IgAN on:
• Safety and tolerability assessed by adverse events (AEs), vital signs, clinical laboratory tests, and electrocardiograms (ECGs)
• Renal function as determined by the rate of change in estimated glomerular filtration rate (eGFR) up to 144 weeks from BOT
• Proteinuria assessed by UPE at 24 weeks from BOT in the subset of patients with baseline high proteinuria (defined as 24-hour UPE ≥ 2 g/day)
• Per-protocol-defined responder at 24 weeks
• Per-protocol-defined partial-responder at 24 weeks
• Time-averaged change in urine protein/creatinine ratio (uPCR)
• Proportion of patients who achieve partial proteinuria remission (24-hour UPE < 0.6 g/day)
• Proportion of patients who achieve complete proteinuria remission (24-hour UPE < 0.3 g/day)
• Proportion of patients who received rescue therapy for IgAN at any time during the study
• Pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of OMS721
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age 18 years or older at the onset of Screening
• Biopsy confirmed diagnosis of IgAN within 10 years prior to Screening
• Proteinuria of > 1 g in 24-hour urine collection at Screening and baseline
• Estimated glomerular filtration rate of ≥ 30 and ≤ 90 mL/min/1.73 m2 at Screening and baseline
• Currently on physician-directed, stable treatment with RAS blockade (ACEIs, ARBs, direct renin inhibitors) and have a systolic BP of < 150 mmHg and a diastolic BP of < 100 mmHg at rest
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E.4 | Principal exclusion criteria |
• Treatment with immunosuppressants (e.g., azathioprine or cyclophosphamide), cytotoxic drugs, or eculizumab within 24 weeks prior to Screening
• Unwilling or unable to discontinue systemic corticosteroids 12 weeks prior to Randomization
• Female patients who are pregnant, breast feeding, or planning to become pregnant up through 12 weeks after the last dose of study drug, including possible retreatments
• Clinical or biological evidence of diabetes mellitus, systemic lupus erythematosus, IgA vasculitis (Henoch Schonlein purpura), secondary IgAN, or other renal disease
• Presence of significant morbidity or other major illness or disease that may confound the interpretation of the clinical trial results or may result in death within 2 years of Screening
• History of renal transplantation
• Have a known hypersensitivity to any constituent of the investigational product
• Rapidly progressive glomerulonephritis, defined as a fall in eGFR of > 30 mL/min/1.73 m2 within 24 weeks or > 15 mL/min/1.73 m2 within 3 months prior to Screening
• Significant abnormalities in clinical laboratory values
• Body mass index ≥ 35 kg/m²
• History of human immunodeficiency virus (HIV), hepatitis B infection (including the presence of isolated anti-hepatitis B core), hepatitis C infection without prior curative treatment and sustained virologic cure, or evidence of immune suppression
• Diagnosis of a malignancy except for adequately treated and cured basal or squamous cell skin cancer, curatively treated in situ disease, or other cancer from which the patient has been disease free for ≥ 5 years
• Have received any other investigational drug or device or experimental procedures within 30 days of the Screening Visit (SV)
• Previously received OMS721
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E.5 End points |
E.5.1 | Primary end point(s) |
• The primary endpoint of this study is the change from baseline in 24-hour UPE at 24 weeks from BOT. |
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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) |
• Safety and tolerability of OMS721 for the treatment of IgAN as assessed by AEs, vital signs, clinical laboratory tests, and ECGs
• The rate of change in eGFR up to 144 weeks from BOT
• Change from baseline in 24-hour UPE at 24 weeks from BOT in patients with baseline 24 hour UPE ≥ 2 g
• Achievement of a treatment response defined as ≥ 30% reduction from baseline in 24 hour UPE at 24 weeks
• Achievement of a partial response defined as a reduction between ≥ 15% and < 30% from baseline in 24-hour UPE at 24 weeks
• Time averaged change from baseline in uPCR through 24 weeks. This will be measured as the time adjusted area-under-the-curve
• Achievement of partial proteinuria remission defined as 24-hour UPE < 0.6 g/day at any time during study
• Achievement of complete proteinuria remission defined as 24-hour UPE < 0.3 g/day at any time during study
• Use of rescue therapy for IgAN at any time during the study
• Change from baseline in eGFR at 24 weeks from BOT
• Pharmacokinetics and pharmacodynamics of OMS721
• Occurrence of ADA and, if present, NAb
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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 | 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 | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
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 | 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 | 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 | 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
| 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 | 42 |
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 |
Australia |
Canada |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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 | 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 |