E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Lupus Nephritis (LN) Immunoglobulin A Nephropathy (IgAN) |
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E.1.1.1 | Medical condition in easily understood language |
Lupus Nephritis (LN) Immunoglobulin A Nephropathy (IgAN) |
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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 | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10025140 |
E.1.2 | Term | Lupus nephritis |
E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
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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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
•To evaluate the efficacy of ALXN2050 to reduce proteinuria in participants with LN or IgAN |
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E.2.2 | Secondary objectives of the trial |
•To evaluate the efficacy of ALXN2050 to improve measures of kidney function in participants with LN or IgAN • PK/PD - To characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of ALXN2050 in participants with LN or IgAN • Safety -To characterize the safety and tolerability of ALXN2050 in participants with LN or IgAN
LN Cohort only: •To evaluate the efficacy of ALXN2050 on measures of kidney function in participants with LN
IgAN Cohort Only: •To evaluate the efficacy of ALXN2050 on measures of kidney function in participants with IgAN
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
LN Cohort • Clinical diagnosis of SLE by 2019 American College of Rheumatology and European League Against Rheumatism criteria. • Diagnosis of 2018 Revised International Society of Nephrology/Renal Pathology Society classification (active focal or diffuse proliferative LN Class III or IV) confirmed by biopsy obtained ≤ 6 months prior to Screening or during Screening Period. Participants may co-exhibit Class V disease. Participants with de novo or relapsing disease may be eligible. • Clinically active LN at Screening requiring/receiving immunosuppression induction treatment in the opinion of the Investigator. • Proteinuria with UPCR ≥ 1 g/g based on one 24 hour urine collection during the Screening Period.
IgAN Cohort • Established diagnosis of primary IgAN based on kidney biopsy obtained any time prior to or during the Screening Period. • Mean proteinuria ≥ 1 g/day on 2 complete and valid 24 hour urine collections during the Screening Period. • For participants with a kidney biopsy performed > 1 year prior to Screening that was used for eligibility: Presence of hematuria as defined by a positive result for blood on urine dipstick or ≥ 10 red blood cells (RBCs)/high power field (hpf) microscopy on urine sediment (documented by the local laboratory) during Screening Period. Presence of hematuria documented by the central laboratory may also be acceptable. • Compliance with stable and optimal dose of RAS inhibitor treatment including maximum allowed or tolerated ACE inhibitor and/or ARB dose for ≥ 3 months prior to Screening with no expected change in dose during the Blinded Treatment Periods (through Week 50) (participants with established intolerance to RAS inhibitors may be included). • Controlled and stable blood pressure (defined as < 140/90 millimeters of mercury [mmHg]) over the past 3 months prior to randomization. |
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E.4 | Principal exclusion criteria |
Both Cohorts: • eGFR ≤ 30 milliliters/minute/1.73 squared meters during Screening calculated by Chronic Kidney Disease Epidemiology Collaboration. • For participants with eGFR < 45 mL/min/1.73 m2 at Screening, presence of any of the following in glomeruli on most recent kidney biopsy prior to or during the Screening Period: a. ≥ 50% interstitial fibrosis and tubular atrophy b. ≥ 50% glomerular sclerosis c. ≥ 50% active crescent formation • Concomitant significant renal disease other than LN or IgAN on the most recent biopsy prior to or during the Screening Period. • History of solid organ or bone marrow transplant, or planned transplant during the Blinded Extended Treatment Period (50 weeks). • Splenectomy or functional asplenia. • Known or suspected complement deficiency, unless attributable to underlying disease (that is, LN and IgAN). • Bone marrow insufficiency with absolute neutrophil count < 1.3 × 10^3/microliter; thrombocytopenia (platelet count < 50,000/cubic millimeter).
For LN Cohort: • Participants who have initiated any of the following treatments for the current active LN flare: a. Cyclophosphamide ≤ 6 months prior to Screening b. CNIs ≤ 1 month prior to Screening c. A cumulative dose of intravenous (IV) methylprednisolone > 3 g d. Mycophenolate mofetil > 2 g/day (or equivalent) for ≥ 8 consecutive weeks prior to Screening e. Prednisone or prednisone equivalent ≥ 0.5 mg/kg/day for ≥ 8 consecutive weeks prior to Screening • Uncontrolled hypertension (systolic blood pressure > 160 mmHg or diastolic blood pressure > 110 mmHg) on 2 or more measurements during the Screening Period.
For IgAN Cohort: • Diagnosis of rapid progressive glomerulonephritis as measured by eGFR loss ≥ 30% over a period of 3 months prior to or during the Screening Period. • Secondary etiologies of IgAN. • Prednisone or prednisone equivalent > 20 mg/day for > 14 consecutive days or any other systemic immunosuppression for the treatment of IgAN ≤ 6 months prior to Screening • Blood pressure of ≥ 140/90 mmHg during the Screening Period confirmed on 2 measures > 30 minutes apart. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1) Percentage change in proteinuria |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1) Week 26 (based on 24-hour urine collection[s]) |
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E.5.2 | Secondary end point(s) |
1) Percentage change in proteinuria 2) Achieving > 30% and > 50% reduction in proteinuria 3)Change from baseline in eGFR 4)PK/PD - Observed plasma concentrations of ALXN2050 5)PK/PD - Absolute values and change from baseline in plasma Bb concentration and serum AP activity 6) Safety - Incidence of TEAEs and TESAEs 7) Safety - Changes from baseline in laboratory assessments
LN Cohort Only: 8) Meeting the criteria for complete renal response (CRR) 9) Meeting the criteria for partial renal response (PRR) 10) Time to the first occurrence of UPCR ≤ 0.5 g/g as measured by spot urine sample 11) Achieving corticosteroid taper to 7.5 mg/day 12) Experience of a Renal Flare 13) Experience of an Extrarenal systemic lupus erythematosus (SLE) Flare 14) Meeting the criteria for treatment failure 15) Meeting the criteria for Suboptimal Response 16) Absolute values and change from baseline in serum albumin
IgAN Cohort Only: 17) Meeting the criteria for partial remission |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 12, Week 26, Week 50 PK/PD and Safety - over time |
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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 | 6 |
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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 28 |
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 |
Argentina |
Peru |
Taiwan |
Australia |
Brazil |
China |
Israel |
Korea, Republic of |
Mexico |
Serbia |
Thailand |
United Kingdom |
United States |
Germany |
Italy |
Spain |
Türkiye |
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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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The end of study is defined as the date the last participant completes the last visit, including the OLE Period and Safety Follow-up Visit. |
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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 | 4 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |