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

Study Overview

• Status: Completed
• Conditions: Glomerulonephritis; Membranous Nephropathy; antiPLA2R Positive
• Intervention / Treatment: Drug: MOR202

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 Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• Georgia
  • Tbilisi, Georgia
    • Managadze National Center of Urology
  • Tbilisi, Georgia
    • Tbilisi State Medical University and Ingorokva High Medical Technology University Clinic
• Germany
  • Aachen, Germany
    • University Hospital Aachen
  • Berlin, Germany
    • Charité
  • Düsseldorf, Germany
    • DaVita Clinical Research
  • Essen, Germany
    • Uniklinikum
  • Mainz, Germany
    • Hospital of Johannes Gutenberg University
• Greece
  • Athens, Greece
    • General Hospital of Athens
  • Heraklion, Greece
    • General Hospital of Heraklion Venizeleio-Papaneio
  • Patras, Greece
    • University General Hospital of Patras
  • Thessaloníki, Greece
    • General Hospital of Thessaloniki
• Korea, Republic of
  • Chuncheon, Korea, Republic of
    • Hallym University Sacred Heart Hospital
  • Jeju, Korea, Republic of
    • Jeju National 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
    • Konkuk University Hospital
• Russian Federation
  • Moscow, Russian Federation
    • Botkin Hospital Moscow
  • Saint Petersburg, Russian Federation
    • First Pavlov State Medical University of St. Petersburg
• Taiwan
  • Kaohsiung, Taiwan
    • Chang Gun Kaog Memorial Hospital
  • New Taipei City, Taiwan
    • Shuang Ho Hospital
  • Taichung, Taiwan
    • China Medical University Hospital
  • Taichung, Taiwan
    • Taichung Veterans General Hospital
  • Taipei, Taiwan
    • National Taiwan University Hospital
• United Kingdom
  • London, United Kingdom
    • Kings College
  • Nottingham, United Kingdom
    • Nottingham Renal and Transplant Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 109/L.
• Neutropenia: Neutrophils < 1.5 x 109/L.
• Leukopenia: Leukocytes < 3.0 x 109/L.
• Hypogammaglobulinemia: Serum immunoglobulins ≤ 4.0 g/L.

Subjects may receive supportive therapies to meet the above criteria

• B-cells < 5 x 106/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 (HbAlc) <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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MOR202 Arm 1; 5 doses administered on Day 1, 8, 15, 29, and 57	Drug: MOR202; 5 or 2 doses of MOR202 will be administered as an intravenous infusion
Experimental: MOR202 Arm 2; 2 doses administered on Day 1 and 15	Drug: MOR202; 5 or 2 doses of MOR202 will be administered as an intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
efficacy: percent change of anti-PLA2R antibody levels	efficacy of 2 different dosing regimens of MOR202 in subjects with anti-PLA2R antibody positive MN	3 months compared to baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
efficacy: immunological complete response (ICR) rate	efficacy of 2 different dosing regimens of MOR202	ICR rate at 3 months, 6 months, 12 months and 24 months
efficacy: overall proteinuria response (OPR) rate	efficacy of 2 different dosing regimens of MOR202	OPR rate at 6 months, 12 months and 24 months.
safety: determined by the frequency, incidence and severity of TEAEs	frequency, incidence and severity of treatment-emergent adverse events	through treatment completion, an average of 3 months per treatment period
PK profile	MOR202 serum concentrations after multiple i.v. administrations	through study completion, an average of 1 year
immunogenicity	number of subjects developing anti-MOR202 antibodies	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: HI-Bio
• Investigators: Study Director: HI-Bio Clinical Program Lead, HI-Bio

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2021
• Primary Completion (Actual): December 14, 2023
• Study Completion (Actual): December 14, 2023

Study Registration Dates

• First Submitted: January 18, 2021
• First Submitted That Met QC Criteria: January 26, 2021
• First Posted (Actual): February 1, 2021

Study Record Updates

• Last Update Posted (Estimated): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 26, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Urologic Diseases; Nephritis; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Glomerulonephritis; Glomerulonephritis, Membranous; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Felzartamab
• Other Study ID Numbers: MOR202C205

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data supporting this study are not publicly available due to the ongoing nature of the clinical development program. Datasets may be available upon reasonable request 18 months after the final clinical study report has been completed and, as appropriate, once the regulatory review of the indication or drug has completed, whichever is later.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No