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 retreatment
•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>30mL/min/1.73m2 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 = 2g/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 = 2g/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 | 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 |
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 |