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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029151 |
E.1.2 | Term | 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 | 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 36 weeks from baseline |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effect of OMS721 in patients with IgAN on: • Proteinuria assessed by 24-hour UPE at 36 weeks from baseline in the subset of patients with high baseline proteinuria (defined as 24-hour UPE ≥ 2 g) • Durability of proteinuria response from 36 weeks • Renal function as determined by the rate of change in estimated glomerular filtration rate (eGFR) up to 144 weeks from baseline • Safety and tolerability • 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 8 years prior to Screening • Documented history of proteinuria of > 1 g/day within 6 months prior to Screening, or uPCR > 0.75 by spot urine at Screening • Mean of two proteinuria measurements > 1 g/day at baseline • Estimated glomerular filtration rate of ≥ 30 mL/min/1.73 m2 at Screening and baseline |
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E.4 | Principal exclusion criteria |
• Treatment with immunosuppressants (e.g., azathioprine or cyclophosphamide), cytotoxic drugs, or eculizumab within 8 weeks prior to Screening, unless such treatment is given for indications other than IgAN • Treatment with systemic corticosteroids within 8 weeks prior to Screening • Uncontrolled BP, a systolic BP of > 150 mmHg and a diastolic BP of >100 mmHg at rest despite the combination of two or more antihypertensives including ACE inhibiters, ARBs, or direct renin inhibitors • 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 Type 1 diabetes mellitus (DM) or poorly controlled DM with hemoglobin A1c > 7.5, or with evidence of diabetic nephropathy on biopsy, systemic lupus erythematosus, IgA Vasculitis (Henoch-Schonlein purpura), secondary IgAN, or other renal disease, during Screening or Run-In • 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 12 weeks prior to Screening. During the Run-In period a patient will be excluded if they experience a decrease in eGFR of > 15 mL/min/1.73 m2 from their best eGFR from the beginning of Screening. • Significant abnormalities in clinical laboratory values including any of the following at the time of evaluation during Screening and Run-In: a. hemoglobin < 9.0 g/dL b. platelet count < 100,000 cells/mm3 c. absolute neutrophil count < 500 cells/mm3 d. alanine transaminase or aspartate transaminase (AST) > 3.0 × the upper limit of normal (ULN) e. serum bilirubin > 2 × ULN • History of human immunodeficiency virus (HIV), evidence of immune suppression, active hepatitis C virus (HCV) infection (patients with positive anti-HCV antibody but a non-detected HCV RNA PCR can enroll), hepatitis B virus (HBV) infection (patients with positive HBsAg are excluded. For patients with isolated positive anti-HBc antibody, HBV DNA test by PCR must be non-detectable to enroll). • 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) or within 5 times the plasma half-life of the administered experimental drug, whichever is longer • Presence of active infection occurring within 7 days of Screening or at the time of Screening |
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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 log-transformed 24-hour UPE in g/day at 36 weeks from baseline |
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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) |
Key Secondary Endpoints • Proteinuria responder, defined as having a 24-hour UPE of at least 50% reduction from baseline as assessed at Week 36 (patients with ≥ 2 g/day UPE at baseline only) • The rate of change in eGFR up to 144 weeks from baseline Other Secondary Endpoints • Time-averaged change from baseline in the log-transformed 24-hour UPE between 36 weeks and 48 weeks • Time-averaged change from baseline in the log-transformed 24-hour UPE between 36 weeks and 72 weeks • Time-averaged 24-hour UPE from 36 weeks to 48 weeks to a level at least 50% reduced from the baseline 24-hour UPE (patients with ≥ 2 g/day UPE at baseline only) • Time-averaged 24-hour UPE from 36 weeks to 72 weeks to a level at least 50% reduced from the baseline 24-hour UPE (patients with ≥ 2 g/day UPE at baseline only) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
36, 48, and 72 weeks for UPE, and 144 week for the rate of change in eGFR. |
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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 | Yes |
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 |
Korea, Republic of |
Malaysia |
Philippines |
Singapore |
Taiwan |
Thailand |
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 |