Efficacy, Safety and PK/PD of MOR202 in Anti-PLA2R+ Membranous Nephropathy (aMN) (NewPLACE)

Phase 2

Completed

Conditions: Glomerulonephritis
antiPLA2R Positive
Membranous Nephropathy

Interventions: Drug: MOR202

Registration Number: NCT04733040

Lead Sponsor: HI-Bio, A Biogen Company

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 24

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MOR202 5 Doses	MOR202	5 doses administered on Day 1, 8, 15, 29, and 57
MOR202 2 Doses	MOR202	2 doses administered on Day 1 and 15

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (25): Chang Gung Memorial Hospital
🇨🇳
Kaohsiung, Taiwan
Managadze National Center of Urology
🇬🇪
Tbilisi, Georgia
University Hospital Aachen
🇩🇪
Aachen, Germany
Charite
🇩🇪
Berlin, Germany
Uniklinikum
🇩🇪
Essen, Germany
General Hospital of Athens
🇬🇷
Athens, Greece
General Hospital of Heraklion Venizeleio-Papaneio
🇬🇷
Heraklion, Greece
General Hospital of Thessaloniki
🇬🇷
Thessaloníki, Greece
Kings College
🇬🇧
London, United Kingdom
Nottingham Renal and Transplant Unit
🇬🇧
Nottingham, United Kingdom
Tbilisi State Medical University and Ingorokva High Medical Technology University Clinic
🇬🇪
Tbilisi, Georgia
DaVita Clinical Research
🇩🇪
Düsseldorf, Germany
Hospital of Johannes Gutenberg University
🇩🇪
Mainz, Germany
University General Hospital of Patras
🇬🇷
Patras, Greece
Hallym University Sacred Heart Hospital
🇰🇷
Chuncheon, Korea, Republic of
JeJu National University Hospital
🇰🇷
Jeju, Korea, Republic of
Konkuk University Hospital
🇰🇷
Seoul, Korea, Republic of
Kyung Hee University Hospital at Gangdong
🇰🇷
Seoul, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷
Seoul, Korea, Republic of
Botkin Hospital Moscow
🇷🇺
Moscow, Russian Federation
First Pavlov State Medical University of St. Petersburg
🇷🇺
Saint Petersburg, Russian Federation
Shuang Ho Hospital
🇨🇳
New Taipei City, Taiwan
China Medical University Hospital
🇨🇳
Taichung, Taiwan
Taichung Veterans General Hospital
🇨🇳
Taichung, Taiwan
National Taiwan University Hospital
🇨🇳
Taipei, Taiwan