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

Glomerulonephritis, Membranous Clinical Trial

— M-PLACE  

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04145440
• Other study ID #: MOR202C103
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: October 15, 2019
• Est. completion date: August 2, 2022

Study information

• Verified date: September 2023
• Source: HI-Bio
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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)

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: August 2, 2022
• Est. primary completion date: January 19, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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).

Related Conditions & MeSH terms

• antiPLA2R Positive
• Glomerulonephritis
• Glomerulonephritis, Membranous

Intervention

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.

Locations

Country	Name	City	State
Australia	Royal Melbourne Hospital	Melbourne	Victoria
Australia	Western Health	Melbourne
Australia	St. George Hospital	Sydney	New South Wales
Belgium	O.L.V. Ziekenhuis	Aalst
Belgium	C.H.U. Brugmann - Site Victor Horta	Brussels
Belgium	Universitair Ziekenhuis Brussels	Brussels
Belgium	Cliniques Universitaires Saint-Luc	Bruxelles
Belgium	UZ Leuven	Leuven
Belgium	CHU de Liège	Liège
France	Groupe Hospitalier Pellegrin - Hôpital Pellegrin	Bordeaux
France	CHU de Grenoble - Hôpital Albert Michallon	Grenoble
France	Hopital Claude Huriez -CHU Lille	Lille
France	Hopital Tenon Service de nephrologie	Paris
France	CHU Saint Etienne - Hôpital Nord	Saint-Priest-en-Jarez
Italy	Azienda Ospedaliera Universitaria Careggi	Firenze
Italy	Ospedale San Raffaele	Milan
Italy	Ospedale Borgo Roma	Verona
Korea, Republic of	Chungnam National University Hospital	Daejeon
Korea, Republic of	Gangnam Severance Hospital	Seoul
Korea, Republic of	Hallym University Kangdong Sacred Heart Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	The Catholic University of Korea	Seoul
Netherlands	Radboud UMC Niimegen Nephrology	Nijmegen
Poland	SPZOZ Centralny Szpital Kliniczny UM w Lodzi	Lódz
Poland	Centrum Zdrowia MDM	Warsaw
Poland	Miedzyleski Szpital Specjalistyczny	Warsaw
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Universitario Reina Sofia	Córdoba
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Puerta de Hierro Majadahonda	Madrid
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Hospital General Universitario de Valencia	Valencia
Spain	Hospital Universitario Dr. Peset	Valencia
United States	North America Research Institute	Azusa	California
United States	The Ohio State University Wexner Medical Center	Columbus	Ohio
United States	MedResearch, Inc	El Paso	Texas
United States	Texas Research Institute	Fort Worth	Texas
United States	GA Nephrology Associates	Lawrenceville	Georgia
United States	University of Miami Division of Nephrology & Hypertension	Miami	Florida
United States	Mayo Clinic	Rochester	Minnesota
United States	UCSF Medical Center	San Francisco	California
United States	Northwest Louisiana Nephrology Research	Shreveport	Louisiana
United States	Kidney Care and Transplant Services of New England, PC	Springfield	Massachusetts
United States	Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center	Torrance	California

Sponsors (1)

Lead Sponsor	Collaborator
HI-Bio

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  France,  Italy,  Korea, Republic of,  Netherlands,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	immunogenicity of MOR202	number of subjects developing anti-MOR202 antibodies	through study completion, an average of 1 year
Secondary	PK profile	serum concentrations after multiple i.v. administrations	through study completion, an average of 1 year
Secondary	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