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

A Phase IIa, Open-Label, 2-Arm Multicenter Clinical Trial to Evaluate the Efficacy, Safety and PK/PD of the Human Anti-CD38 Antibody MOR202 in Anti-PLA2R Antibody Positive Membranous Nephropathy (NewPLACE)

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

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.

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.