Trial to Assess Safety and Efficacy of MOR202 in Anti-PLA2R + Membranous Nephropathy (aMN) (M-PLACE)

A Phase Ib/IIa, Open-Label, Multicenter Clinical Trial to Assess Safety and Efficacy of the Human Anti-CD38 Antibody MOR202 in Anti-PLA2R Antibody Positive Membranous Nephropathy (aMN)

This is an open-label, multicentre study to characterize the safety and efficacy of the human anti-CD38 antibody MOR202 in adult subjects with in Anti-PLA2R Antibody Positive Membranous Nephropathy (newly diagnosed/relapsed/refractory)

Study Overview

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

Detailed Description

After treatment subjects will be observed for up to 1 year.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Melbourne, Australia, 3021
    • Western Health
  • New South Wales
    • Sydney, New South Wales, Australia, 2217
      • St. George Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3050
      • Royal Melbourne Hospital
• Belgium
  • Aalst, Belgium, 9300
    • O.L.V. Ziekenhuis
  • Brussels, Belgium, 1020
    • C.H.U. Brugmann - Site Victor Horta
  • Brussels, Belgium, 1090
    • Universitair Ziekenhuis Brussels
  • Bruxelles, Belgium, 1200
    • Cliniques Universitaires Saint-Luc
  • Leuven, Belgium, 3000
    • UZ Leuven
  • Liège, Belgium, 4000
    • CHU de Liège
• France
  • Bordeaux, France, 33000
    • Groupe Hospitalier Pellegrin - Hôpital Pellegrin
  • Grenoble, France, 38043
    • CHU de Grenoble - Hôpital Albert Michallon
  • Lille, France, 59037
    • Hopital Claude Huriez -CHU Lille
  • Paris, France, 75020
    • Hopital Tenon Service de nephrologie
  • Saint-Priest-en-Jarez, France, 42055
    • CHU Saint Etienne - Hopital Nord
• Italy
  • Firenze, Italy, 50134
    • Azienda Ospedaliera Universitaria Careggi
  • Milan, Italy, 20132
    • Ospedale San Raffaele
  • Verona, Italy, 37124
    • Ospedale Borgo Roma
• Korea, Republic of
  • Daejeon, Korea, Republic of, 35015
    • Chungnam National University Hospital
  • Seoul, Korea, Republic of
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of, 05355
    • Hallym University Kangdong Sacred Heart Hospital
  • Seoul, Korea, Republic of, 06273
    • Gangnam Severance Hospital
  • Seoul, Korea, Republic of, 06591
    • The Catholic University of Korea
• Netherlands
  • Nijmegen, Netherlands, 6525 GA
    • Radboud UMC Niimegen Nephrology
• Poland
  • Warsaw, Poland, 00631
    • Centrum Zdrowia MDM
  • Warsaw, Poland, 04749
    • Miedzyleski Szpital Specjalistyczny
  • Łódź, Poland, 92213
    • SPZOZ Centralny Szpital Kliniczny UM w Lodzi
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clínic de Barcelona
  • Barcelona, Spain, 8035
    • Hospital Universitari Vall d'Hebron
  • Córdoba, Spain, 50134
    • Hospital Universitario Reina Sofia
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28222
    • Hospital Universitario Puerta de Hierro Majadahonda
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen Del Rocio
  • Valencia, Spain, 46017
    • Hospital Universitario Dr. Peset
  • Valencia, Spain, 46014
    • Hospital General Universitario de Valencia
• United States
  • California
    • Azusa, California, United States, 91702
      • North America Research Institute
    • San Francisco, California, United States, 94143
      • UCSF Medical Center
    • Torrance, California, United States, 90502
      • Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Division of Nephrology & Hypertension
  • Georgia
    • Lawrenceville, Georgia, United States, 30046
      • GA Nephrology Associates
  • Louisiana
    • Shreveport, Louisiana, United States, 71101
      • Northwest Louisiana Nephrology Research
  • Massachusetts
    • Springfield, Massachusetts, United States, 01107
      • Kidney Care and Transplant Services of New England, PC
  • Minnesota
    • Rochester, Minnesota, United States, 55902
      • Mayo Clinic
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center
  • Texas
    • El Paso, Texas, United States, 79905
      • MedResearch, Inc
    • Fort Worth, Texas, United States, 76248
      • Texas Research Institute

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

• > 18 to < 80 years (at date of signing informed consent form [ICF]).
• Urine protein to creatinine ratio (UPCR) of ≥ 3.000 g/g OR proteinuria ≥ 3.500 g/24 h from 24-h urine at screening
• Active anti-PLA2R antibody positive MN in need of immunosuppressive therapy (IST) according to investigator judgement and diagnosed on the basis of a biopsy, archival biopsy acquired within 5 years prior to screening is acceptable.
• Estimated glomerular filtration rate ≥ 50 ml/min/1.73m² or ≥ 30 and <50 ml/min/1.73m², and interstitial fibrosis and tubular atrophy score of less than 25% on a renal biopsy obtained within the last 6 months prior to start of screening.
• Not in spontaneous remission despite proper treatment with ACEIs, ARBs (sufficient dose and treatment duration) as per clinical practice and scientific guidelines. If the subject is intolerant to an ACEI or ARB, the reason must be documented and approval obtained prior to enrolment.
• Systolic blood pressure BP ≤150 mmHg and diastolic BP ≤100 mmHg after 5 minutes of rest
• Vaccinated against Pneumococcus within the last 3 years prior to date of signing informed consent (subjects may be vaccinated during screening to meet this criterion; interval to first dose of MOR202 must be at least 14 days).
• Cohort 1 comprises newly diagnosed or relapsed subjects: Serum anti-PLA2R antibodies ≥50.0 RU/mL
• Cohort 2 comprises therapy refractory subjects: a Subject did not achieve immunological remission after prior IST(s) as documented by the investigator AND b Subject is without promising standard therapeutic options as documented by the investigator (i.e. investigator expects efficacy or safety issues with remaining IST options) AND c Serum anti-PLA2R antibodies ≥ 20.0 RU/mL measured at screening

Note: France will only enroll patients in Cohort 2.

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.
• Secondary cause of MN (e.g. Systemic lupus erythematosus, medications, malignancies)
• Concomitant renal disease other than MN (e.g., diabetic renal disease, lupus nephritis, IgA nephropathy).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Patients with newly diagnosed or relapsed membranous nephropathy	Drug: MOR202; Patients will receive 9 doses of MOR202 as an intravenous infusion over 6 treatment cycles of 28-days each. Dosing will occur weekly in Cycle 1 and every 4 weeks in Cycles 2 to 6.
Experimental: Cohort 2; Patients with membranous nephropathy refractory to immunosuppressive treatment	Drug: MOR202; Patients will receive 9 doses of MOR202 as an intravenous infusion over 6 treatment cycles of 28-days each. Dosing will occur weekly in Cycle 1 and every 4 weeks in Cycles 2 to 6.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
safety and tolerability: incidence and severity of treatment-emergent adverse events	incidence and severity of treatment-emergent adverse events	at end of treatment phase (after 6 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
effect of MOR202 on serum anti-PLA2R antibodies	best Immunological Response based on reduction of serum anti-PLA2R antibody titer	through study completion, an average of 1 year
immunogenicity of MOR202	number of subjects developing anti-MOR202 antibodies	through study completion, an average of 1 year
PK profile	serum concentrations after multiple i.v. administrations	through study completion, an average of 1 year
safety in the follow-up phase: incidence and severity of adverse events (AEs) in the follow-up phase	incidence and severity of adverse events (AEs) in the follow-up phase	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): October 15, 2019
• Primary Completion (Actual): January 19, 2022
• Study Completion (Actual): August 2, 2022

Study Registration Dates

• First Submitted: October 18, 2019
• First Submitted That Met QC Criteria: October 28, 2019
• First Posted (Actual): October 30, 2019

Study Record Updates

• Last Update Posted (Actual): September 29, 2023
• Last Update Submitted That Met QC Criteria: September 25, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Kidney Diseases; Urologic Diseases; Nephritis; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Glomerulonephritis; Glomerulonephritis, Membranous; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Felzartamab
• Other Study ID Numbers: MOR202C103

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: Yes
• Studies a U.S. FDA-regulated device product: No