E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary glomerular disease and persistent proteinuria |
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E.1.1.1 | Medical condition in easily understood language |
Primary proteinuric renal disease |
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E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
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 | 10037032 |
E.1.2 | Term | Proteinuria |
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 efficacy of ANG-3070 in patients with primary glomerular disease and persistent proteinuria while on the SOC, as measured by a reduction in urinary protein excretion as measured by urinary protein/creatinine ratio (UPCR). |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of ANG-3070 in patients with primary glomerular disease and persistent proteinuria. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female participants aged 18 and older. 2. Diagnosis of IgA nephropathy or primary FSGS confirmed by renal biopsy at any time in the past, except for patients with type II diabetes who must have had a renal biopsy within prior 5 years showing no evidence of diabetic kidney disease. Participants with genetic forms of FSGS may be enrolled without a renal biopsy if the clinical picture is consistent with the genetic testing results and they are on the standard of care therapy for at least 12 weeks prior to enrollment in the study. 3. Estimated glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) ≥ 30 mL/min/1.73m2. 4. Urinary protein excretion, as measured by UPCR (geometric mean of 3 first-void urine), per threshold values below: a) IgA nephropathy: ≥ 750 mg/g or 85 mg/mmol of creatinine b) FSGS ≥ 1000 mg/g or 113 mg/mmol of creatinine 5. Stable blood pressure ≤ 140/90 mmHg with stable antihypertensive regimen for at least 12 weeks prior to screening. 6. All participants must be on the SOC therapy including the maximally tolerated/recommended doses of an Angiotensin-converting enzyme inhibitor (ACEi) or ARB, but not both. 7. Renin-angiotensin-aldosterone system (RAAS) blockers and Sodium glucose co-transporter 2 (SGLT-2) inhibitors must be stable (optimized, established dose) for at least 12 weeks prior to screening and projected to remain stable through week 16 (dose adjustment allowed if clinically indicated). 8. Immunosuppressive or immunomodulatory therapy must be stable (optimized, established dose) for at least 12 weeks prior to screening and projected to remain stable through study week 16 (dose adjustment allowed if clinically indicated). 9. Both genders of childbearing potential must agree to use adequate contraception, during and for at least 3 months after the last dose of study drug. 10. Participants must be willing and able to give written Informed Consent and to comply with protocol requirements. 11. Participants must be judged to be otherwise fit for the study by the Investigator. |
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E.4 | Principal exclusion criteria |
Laboratory and Assessments 1. Positive Hepatitis B (HBV), Hepatitis C (HCV), or human immunodeficiency virus (HIV) viral screening test; historical or during the screening. 2. Hematologic abnormalities as follows: Hemoglobin (Hb) <8 g/dL, or platelets <50,000, or absolute neutrophil count (ANC) <1000 cells/μL at baseline. 3. Aspartate Aminotransferase (AST) or alanine Aminotransferase (ALT) or total bilirubin > 2 ULN. 4. Hemoglobin A1C > 8.5% (only for patients with history of diabetes).
Excluded Medications 5. Participants taking non-steroidal anti-inflammatory agents (NSAIDS) chronically (intermittent, i.e., occasional NSAIDS for pain or fever is discouraged, but is not excluded). No NSAIDS allowed within 72 hours of the scheduled lab work to determine eGFR and/or urinary protein and creatinine measurements. 6. Participants taking strong inducers (e.g., phenytoin, rifampin) or inhibitors (e.g., clarithromycin, itraconazole) of CYP3A4. Please see Appendix 1.
Bleeding or Thrombosis Risk 7. Known predisposition to bleeding. 8. Participants who require fibrinolysis, full-dose therapeutic anticoagulation (e.g. vitamin K antagonists, dabigatran, heparin, hirudin etc.), or high dose antiplatelet therapy. Prophylactic use of antiplatelet therapy (e.g. acetyl salicylic acid up to 325 mg/d, or clopidogrel at 75 mg/d, or equivalent doses of other antiplatelet therapy) is not excluded. 9. History of hemorrhagic central nervous system (CNS) event within 12 months of the screening visit. 10. History of active gastrointestinal bleeding within 6 months of the Screening visit. 11. History of thrombotic event (including stroke and transient ischemic attacks) within 12 months of the Screening visit.
Other excluding conditions and medical judgement 12. Type I diabetes mellitus. 13. Histopathological evidence of diabetic kidney disease on the renal biopsy. 14. Membranous nephropathy. 15. Myocardial infarction or unstable angina within 6 months of the screening visit. 16. History of solid organ or hematopoietic cell transplantation. 17. On an organ transplant waiting list or anticipated organ transplant within 6 months of screening. 18. History of treated Hepatitis C (HCV). 19. Participation in any clinical study of an investigational product within 12 weeks from the date of screening. 20. History or presence of any form of cancer within 2 years of screening except excised basal or squamous cell carcinoma of the skin. 21. Renal disease secondary to systemic disease including but not limited to: systemic lupus erythematosus, anti-neutrophil cytoplasmic antibodies -associated diseases, anti-glomerular basement disease, secondary forms of focal segmental glomerulosclerosis, renal diseases associated with para-proteinemias, C3 glomerulopathy, and diabetic kidney disease. 22. Treatment with Anti-CD20 monoclonal antibodies within 6 months prior to screening. 23. A known systemic disorder that requires, or is expected to require, systemic glucocorticoids or immune modulators during the study. 24. BMI ≥40 Kg/m2 25. Pregnant women or women who are breast feeding or of child-bearing potential not willing to use two effective methods of birth control (1 barrier and 1 highly effective non-barrier) during the study from screening until 3 months after end of treatment. 26. Sexually active males not committing to using condoms during the study (except if their partner is not of childbearing potential) and 3 months after end of treatment. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage change in urinary protein excretion at Week 12, as measured by UPCR |
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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) |
measured by UPCR (urinary albumin/creatinine ratio) • Number of patients with complete remission in proteinuria, defined as UPCR of < 0.2 g/g of creatinine at Week 12. • Number of patients with partial remissions in proteinuria, defined as UPCR reduction of ≥ 50% from the baseline and UPCR < 3.5 g/g if the baseline UPCR was > 3.5 g/g of creatinine at Week 12. • Number of patients with ≥ 50% reduction in UPCR from the baseline at Week 12. • Number of patients with ≥ 50% reduction in UACR from the baseline at Week 12. • Percentage change from baseline in eGFR at Week 12. • Changes in serum albumin, fasting triglycerides, and cholesterol at Week 12. |
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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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | 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 | 4 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
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 |
Georgia |
United States |
Lithuania |
Bulgaria |
Spain |
Italy |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |