| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
| Berger´s disease, Inflammation of the kidney. |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Symptoms and general pathology [C23] |
| MedDRA Classification |
| 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 | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| Evaluate the effect of atacicept compared to placebo on change in proteinuria in adult subjects with IgAN |
|
| E.2.2 | Secondary objectives of the trial |
- Evaluate the effect of atacicept compared to placebo on change in proteinuria in adult subjects with IgAN
- Evaluate the effect of atacicept on change in proteinuria in adult subjects with IgAN
- Evaluate the effect of atacicept on rate of change in estimated glomerular filtration rate (eGFR)
- Evaluate the effect of atacicept on change in serum immunoglobulin levels, complement levels and on serum Gd-IgA1 levels
- Evaluate the safety and tolerability of atacicept
- Evaluate serum PK of atacicept |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Must have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study assessments
2. Adult male or female of ≥18 years of age, or as per country specific legally or nationally recognized adult age, who provide written informed consent prior to performing any study assessments
3. Diagnosis of IgAN as demonstrated by renal biopsy conducted within 10 years of the Screening Visit
4. Total urine protein excretion > 0.75g per 24-hour or UPCR > 0.75mg/mg based on a 24-hour urine sample during the Screening Period
5. eGFR ≥ 30 mL/min/1.73 m2 at screening as per the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
6. On a stable prescribed regimen of RAASi for at least 12 weeks that is at the maximum labeled or tolerated dose at screening.
• The subject is eligible if they do not tolerate RAASi, provided their management of IgAN is SoC according to local guidelines. This must be documented by the Investigator.
7. Systolic blood pressure ≤150 mmHg and diastolic blood pressure ≤90 mmHg at screening
8. A female is eligible if she is not pregnant (i.e., after a confirmed menstrual period, a negative serum pregnancy test at screening and negative urine pregnancy test at Day 1), not breastfeeding (for at least 3 months prior to screening), and at least one of the following conditions applies:
• Is not a woman of childbearing potential (WOCBP).
OR
• Is a WOCBP who agrees to use a highly effective contraceptive method (i.e., has a failure rate of less than 1% per year), as listed in Appendix 2, at least 7 days prior to randomization through 175 days after the last dose of study drug. See Appendix 2 for further details. |
|
| E.4 | Principal exclusion criteria |
1.IgAN secondary to another condition (e.g., liver cirrhosis), or other causes of mesangial IgA deposition including IgA vasculitis (i.e.,Henoch-Schonlein purpura),SLE,dermatitis herpetiformis, ankylosing spondylitis
2.Evidence of rapidly progressive glomerulonephritis (loss of ≥50% of eGFR within 3 months of screening
3.Evidence of nephrotic syndrome within 6 months of screening (serum albumin <30g/L in association with UPCR>3.5mg/mg
4. Total urine protein excretion ≥5g per 24-hour or urine protein to creatinine ratio (UPCR)≥5mg/mg based on a 24-hour urine sample during Screening
5.Renal or other organ transplantation prior to, or expected during, the study with the exception of corneal transplants
6.Concomitant chronic renal disease in addition to IgAN(e.g., diabetic nephropathy, primary focal segmental glomerulosclerosis (FSGS), membranous nephropathy,C3 glomerulopathy, lupus nephritis)
7.Uncontrolled diabetes, defined as hemoglobin-A1c (HbA1c)>7.5% at screening
8.History of tuberculosis(TB), untreated latent TB infection(LTBI), or evidence of active TB determined by a positive Quantiferon test at the Screening Visit.
9.Prohibited medications:
•Use of systemic corticosteroids or immunosuppressive medications (e.g., MMF, azathioprine, cyclophosphamide, hydroxychloroquine) for the treatment of IgAN within 3 months prior to screening or expected use during the study.
•For non-IgAN indications (e.g., gout flare, exacerbation of asthma, severe rash, etc):
•Within 3 months prior to randomization: Use of systemic corticosteroids or immunosuppressive medications for>1 week or 0.5mg/kg/day prednisolone or equivalent
•Use of B-cell–directed biologic therapies including blisibimod, belimumab, rituximab, ocrelizumab for any period of time
•Use of other biologics (e.g.,anti-TNF, abatacept,anti-IL-6) and investigational biologics
10.Clinically significant or predefined abnormalities per central laboratory tests, at the Screening Visit, meeting any of the criteria below:
•serum IgG below 7g/L
•aspartate aminotransferase, alanine aminotransferase or alkaline phosphatase level >2.5 × upper limit of normal (ULN) or total bilirubin >1.5 x ULN.
i.If subject has a known history of Gilberts (history of isolated increase in total bilirubin without increase in liver transaminases), contact the Medical Monitor for further discussion.
11.Administration of live and live-attenuated vaccinations within 30 days prior to randomization
12.History or current diagnosis of any demyelinating disease such as, but not restricted to, multiple sclerosis (MS) or optic neuritis (ON)
13.Patients with history of unstable angina, Class III and IV congestive heart failure and/or clinically significant arrhythmia, as judged by the Investigator.
14.Any condition, including any uncontrolled disease state other than IgAN, that in the opinion of the Investigator or the Sponsor/designee constitutes an inappropriate risk or a contraindication for participation in the study or that could interfere with the study objectives, conduct or evaluation
15.Active clinically significant viral, bacterial or fungal infection, or any major episode of infection requiring hospitalization or treatment with parenteral anti-infectives within 4 weeks prior to, or during the Screening Visit, or completion of oral anti-infectives within 2 weeks prior to, or during the Screening Visit or a history of recurrent infections (i.e., 3 or more of the same type of infection in a 12-month rolling period).Vaginal candidiasis, onychomycosis and genital or oral herpes simplex virus considered by the Investigator to be sufficiently controlled are not exclusionary.
16.History of acute or chronic infection with human immunodeficiency virus, hepatitis C virus, or hepatitis B virus.Positive hepatitis B surface antigen (HBsAg): Subjects who are HBsAg negative and hepatitis B core antibody (HBcAb) positive with no detectable hepatitis B virus (HBV) DNA are eligible but will require monthly HBV DNA monitoring through safety follow-up.
17.History of splenectomy
18.History of malignancy (hematologic or solid tumor) within 5 years prior to Screening Visit, except adequately treated basal cell or squamous cell carcinomas of the skin (no more than 3 lesions requiring treatment in lifetime) or carcinoma in situ/cervical intraepithelial neoplasia of the uterine cervix
19.Known hypersensitivity to atacicept or any component of the formulated atacicept
20.Major surgery within 6 weeks prior to the Screening Visit or planned/expected major surgery during the study period
21.Clinically significant history of alcohol or drug abuse in the 1 year prior to the Screening Visit as per Investigator opinion
22.Unwillingness or lack of capacity to follow all study procedures
23.Treatment with other investigational agents within the last 4 weeks or 5 half-lives, whichever is longer, prior to the Screening Visit. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Urine protein to creatinine ratio (UPCR) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
- Urine protein to creatinine ratio (UPCR)
- Urine protein to creatinine ratio (UPCR)
- Rate of change in eGFR
- IgA, IgG, IgM levels, C3 and C4 levels. Gd-IgA1 levels
- Routine clinical and laboratory tests, and AEs
- Serum concentration of atacicept |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Week 36
- Weeks 12, 48 and 96
- Weeks 12, 24, 36, 48 and 96
- Weeks 12, 24, 36, 48, 96 and Follow Up Weeks 12 and 26
- Entire Study
- Entire Study |
|
| 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 | 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 26 |
| 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 |
| India |
| Malaysia |
| United States |
| Turkey |
| Belgium |
| Czechia |
| Germany |
| Greece |
| Poland |
| Korea, Republic of |
| United Kingdom |
|
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 7 |
| E.8.9.2 | In all countries concerned by the trial days | 29 |
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