antiPLA2R Positive, Glomerulonephritis, Membranous Nephropathy
Conditions
Brief summary
This 2-arm, multi-center, open-label, parallel-group phase II trial will assess the efficacy, safety and pharmacokinetics/pharmacodynamics of the human antibody MOR202 in subjects with anti-PLA2R antibody-positive membranous nephropathy indicated for immunosuppressive therapy
Detailed description
After treatment, subjects will enter a repeat treatment period (3 months) if necessary; and a final follow-up period of 15 to 18 months. Study Sponsor, originally HI-Bio, Inc., is now HI-Bio, A Biogen Company.
Interventions
DRUGMOR202
MOR202 will be administered as an intravenous infusion
Sponsors
HI-Bio, A Biogen Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Subjects ≥ 18 to ≤ 80 years (at date of signing the informed consent form \[ICF\]). * Urine protein to creatinine ratio (UPCR) of ≥ 3.0 g/g or proteinuria ≥ 3.5 g/24 h * Estimated glomerular filtration rate (eGFR) ≥ 50 ml/min/1.73 m² (eGFR \>30 and \< 50 ml/min/1.73 m² can be included provided an interstitial fibrosis and tubular atrophy (IFTA) score of \< 25% in a kidney biopsy) * Not in spontaneous remission despite proper treatment with angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARBs) (sufficient dose and treatment duration) as per clinical practice and scientific guidelines. If the subject is intolerant to ACEI and ARBs, the reason must be documented and approval for enrollment be obtained from the Medical Monitor. * Systolic blood pressure (BP) ≤150 mmHg and diastolic BP ≤100 mmHg after 5 minutes of rest. * Serum anti-PLA2R antibodies ≥ 50.0 RU/mL determined by Euroimmun ELISA. * Female subjects: A female is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: 1. Not a female of childbearing potential (FCBP) 2. A FCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 3 months after the last dose of MOR202 Key
Exclusion criteria
* Hemoglobin \< 80 g/L. * Thrombocytopenia: Platelets \< 100.0 x 10\^9/L. * Neutropenia: Neutrophils \< 1.5 x 10\^9/L. * Leukopenia: Leukocytes \< 3.0 x 10\^9/L. * Hypogammaglobulinemia: Serum immunoglobulins ≤ 4.0 g/L. Subjects may receive supportive therapies to meet the above criteria * B-cells \< 5 x 10\^6/L * Diabetes mellitus type 2: Subjects with type 2 diabetes mellitus may only enter the clinical trial if a kidney biopsy performed within 6 months prior to screening shows MN without evidence of diabetic nephropathy and diabetes is controlled, as shown by: 1. Glycated hemoglobin (HbA1c) \<8.0 % or 64 mmol/mol. 2. No diabetic retinopathy known. 3. No peripheral neuropathy known. * Total bilirubin, aspartate aminotransferase or alanine aminotransferase \>1.5 x ULN, alkaline phosphatase \>3.0 x ULN.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| efficacy: percent change of anti-PLA2R antibody levels | 3 months compared to baseline | efficacy of 2 different dosing regimens of MOR202 in subjects with anti-PLA2R antibody positive MN |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| efficacy: immunological complete response (ICR) rate | ICR rate at 3 months, 6 months, 12 months and 24 months | efficacy of 2 different dosing regimens of MOR202 |
| efficacy: overall proteinuria response (OPR) rate | OPR rate at 6 months, 12 months and 24 months. | efficacy of 2 different dosing regimens of MOR202 |
| safety: determined by the frequency, incidence and severity of TEAEs | through treatment completion, an average of 3 months per treatment period | frequency, incidence and severity of treatment-emergent adverse events |
| PK profile | through study completion, an average of 1 year | MOR202 serum concentrations after multiple i.v. administrations |
| immunogenicity | through study completion, an average of 1 year | number of subjects developing anti-MOR202 antibodies |
Countries
Georgia, Germany, Greece, Russia, South Korea, Taiwan, United Kingdom
Outcome results
None listed