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

Glomerulonephritis Clinical Trial

— NewPLACE  

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04733040
• Other study ID #: MOR202C205
• Status: Completed
• Phase: Phase 2
• Start date: January 20, 2021
• Est. completion date: December 14, 2023

Study information

• Verified date: February 2024
• Source: HI-Bio
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: December 14, 2023
• Est. primary completion date: December 14, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• antiPLA2R Positive
• Glomerulonephritis
• Glomerulonephritis, Membranous
• Kidney Diseases
• Membranous Nephropathy

Intervention

Drug:
• MOR202
5 or 2 doses of MOR202 will be administered as an intravenous infusion

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
HI-Bio

Countries where clinical trial is conducted

Georgia,  Germany,  Greece,  Korea, Republic of,  Russian Federation,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	efficacy: overall proteinuria response (OPR) rate	efficacy of 2 different dosing regimens of MOR202	OPR rate at 6 months, 12 months and 24 months.
Secondary	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
Secondary	PK profile	MOR202 serum concentrations after multiple i.v. administrations	through study completion, an average of 1 year
Secondary	immunogenicity	number of subjects developing anti-MOR202 antibodies	through study completion, an average of 1 year