E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Lupus Nephritis (LN)
Immunoglobulin A Nephropathy (IgAN) |
|
E.1.1.1 | Medical condition in easily understood language |
Lupus Nephritis (LN)
Immunoglobulin A Nephropathy (IgAN) |
|
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 |
|
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 |
|
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 ravulizumab compared with placebo to reduce proteinuria in adult participants with LN or IgAN |
|
E.2.2 | Secondary objectives of the trial |
Safety and tolerability of ravulizumab and additional efficacy measures |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Common to both disease cohorts:
- 18 - 75 years of age
- Proteinuria ≥ 1 (g/d or g/g)
- Vaccinated against meningococcal infection
- Vaccinated against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae
For LN cohort:
- Diagnosis of active focal or diffuse proliferative LN Class III or IV
- Clinical active LN, requiring/receiving immunosuppression induction treatment
For IgAN cohort:
- Diagnosis of primary IgAN
- Compliance with stable and optimal dose of RAS inhibitor treatment for ≥ 3 months
- For participants with a kidney biopsy used for eligibility > 1 year prior to Screening: Presence of hematuria as defined by a positive result on urine dipstick for blood or ≥ 10 red blood cell (RBC)/hpf microscopy on urine sediment (as documented by the local laboratory). Presence of hematuria documented by the central laboratory may also be acceptable. Participants with established intolerance to RAS inhibitors may be included
For a full list of inclusion criteria please refer to the clinical study protocol, section 5.1. |
|
E.4 | Principal exclusion criteria |
Common to both disease cohorts:
- Estimated GFR < 30 mL/min/1.73 m2
- For patients with eGFR < 45 mL/min/1.73 m2 at Screening, presence of any of the following in glomeruli on most recent kidney biopsy prior or during the Screening Period:
≥ 50% interstitial fibrosis and tubular atrophy
≥ 50% glomerular sclerosis,
≥ 50% active crescent formation
- Previously received a complement inhibitor (eg, eculizumab) at any time
- Concomitant significant renal disease other than LN or IgAN
- History of other solid organ or bone marrow transplant
- Uncontrolled hypertension
- Institutionalization by administrative or court order or known medical or psychological condition or risk factor that, in the opinion of the Investigator, might interfere with the participant's full participation in the study
- Known history of human immunodeficiency virus (HIV) infection
- Hypersensitivity to any ingredient contained in the study drug
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. Calcineurin inhibitors ≤ 3 months prior to Screening
c. A cumulative dose of IV methylprednisolone > 3 g
d. Mycophenolate mofetil > 2 g/day (or equivalent) for ≥ 4 consecutive weeks prior to Screening
e. Oral corticosteroids ≥ 0.5 mg/kg/day for ≥ 4 consecutive weeks prior to Screening
For IgAN cohort:
- Diagnosis of rapid progressive glomerulonephritis
- Prednisone or prednisone equivalent > 20 mg/day for > 14 consecutive days or any other immunosuppression for the treatment of
IgAN ≤ 6 months prior to Screening
- Body mass index ≥ 38 kg/m2
For a full list of exclusion criteria please refer to the clinical study protocol, section 5.2. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Percentage change in proteinuria |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Common to both disease cohorts:
- Percentage change in proteinuria
- Change from baseline in eGFR
For LN:
- Percentage of participants meeting the criteria for Complete Renal Response
- Percentage of participants meeting the criteria for Partial Renal Response
- Time to UPCR (Urine Protein to Creatinine Ratio) < 0.5 g/g
- Percentage of participants achieving corticosteroid taper to 7.5 mg/day
- Percentage of participants with Renal Flare
- Percentage of participants with Extrarenal SLE (Systemic Lupus Erythematosus) Flare
- Percentage of participants with Suboptimal Response through Week 50
For IgAN:
- Percentage of participants meeting the criteria for Partial Remission |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Throughout, Week 26 and/or Week 50 |
|
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 | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
|
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 | 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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
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 |
Singapore |
United States |
Belgium |
France |
Germany |
Italy |
Netherlands |
Poland |
Spain |
Sweden |
Korea, Republic of |
Taiwan |
United Kingdom |
|
E.8.7 | Trial has a data monitoring committee | No |
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
|
|
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 | 0 |
E.8.9.1 | In the Member State concerned days | 7 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial days | 3 |