Clinical trial NCT04145440: Trial to Assess Safety and Efficacy of MOR202 in Anti-PLA2R + Membranous Nephropathy (aMN)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Glomerulonephritis, Membranous
antiPLA2R Positive
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2019-10-30
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: 2 cohorts by disease status (Cohort 1: Patients with newly diagnosed or relapsed membranous nephropathy; Cohort 2: Patients with membranous nephropathy refractory to immunosuppressive treatment)
Primary purpose: TREATMENT

Brief 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)

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

Study Sponsor, originally HI-Bio, Inc., is now HI-Bio, A Biogen Company.

Eligibility criteria: 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 5 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).

Primary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: Week 1 to Week 24
measure: Percentage of Participants With Adverse Events
timeFrame: Week 1 to Week 24
Secondary outcomes:
measure: Best Immunological Response Rate (BIRR)
timeFrame: Up to 52 weeks
measure: Number of Participants Tested Positive for Anti-felzartamab Antibodies
timeFrame: Baseline; Up to 52 weeks
measure: Percentage of Participants Tested Positive for Anti-felzartamab Antibodies
timeFrame: Baseline; Up to 52 weeks
measure: Antibody Titers of Participants Tested Positive for Anti-felzartamab Antibodies
timeFrame: Baseline; Up to 52 weeks
measure: Felzartamab Serum Concentrations After Multiple Intravenous Administrations
timeFrame: Pre Dose and Post Dose on Cycle 1 Day 1 (C1D1), C1D8, C1D15, C1D22, C2D1, C3D1, C4D1, C5D1, C6D1, End of Treatment (week 24), Follow-up visit (week 38), End of Study (up to 52 weeks)
measure: Number of Participants With AEs During the Follow-up Period
timeFrame: Week 25 to Week 52
measure: Percentage of Participants With AEs During the Follow-up Period
timeFrame: Week 25 to Week 52
Other outcomes:
Locations:
city: Azusa
country: United States
facility: North America Research Institute
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center
state: California
city: Torrance
country: United States
facility: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
state: California
city: Miami
country: United States
facility: University of Miami Division of Nephrology & Hypertension
state: Florida
city: Lawrenceville
country: United States
facility: GA Nephrology Associates
state: Georgia
city: Shreveport
country: United States
facility: Northwest Louisiana Nephrology Research
state: Louisiana
city: Springfield
country: United States
facility: Kidney Care and Transplant Services of New England, PC
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: El Paso
country: United States
facility: MedResearch, Inc
state: Texas
city: Fort Worth
country: United States
facility: Texas Research Institute
state: Texas
city: Sydney
country: Australia
facility: St. George Hospital
state: New South Wales
city: Melbourne
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Western Health
city: Aalst
country: Belgium
facility: O.L.V. Ziekenhuis
city: Brussels
country: Belgium
facility: C.H.U. Brugmann - Site Victor Horta
city: Brussels
country: Belgium
facility: Universitair Ziekenhuis Brussels
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Leuven
country: Belgium
facility: UZ Leuven
city: Liège
country: Belgium
facility: CHU de Liège
city: Bordeaux
country: France
facility: Groupe Hospitalier Pellegrin - Hôpital Pellegrin
city: Grenoble
country: France
facility: CHU de Grenoble - Hôpital Albert Michallon
city: Lille
country: France
facility: Hopital Claude Huriez -CHU Lille
city: Paris
country: France
facility: Hopital Tenon Service de nephrologie
city: Saint-Priest-en-Jarez
country: France
facility: CHU Saint Etienne - Hôpital Nord
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi
city: Milan
country: Italy
facility: Ospedale San Raffaele
city: Verona
country: Italy
facility: Ospedale Borgo Roma
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital
city: Seoul
country: Korea, Republic of
facility: Hallym University Kangdong Sacred Heart Hospital
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Nijmegen
country: Netherlands
facility: Radboud UMC Niimegen Nephrology
city: Warsaw
country: Poland
facility: Centrum Zdrowia MDM
city: Warsaw
country: Poland
facility: Miedzyleski Szpital Specjalistyczny
city: Łódź
country: Poland
facility: SPZOZ Centralny Szpital Kliniczny UM w Lodzi
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro Majadahonda
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital Universitario Dr. Peset
Study officials:
affiliation: HI-Bio, A Biogen Company
name: Medical Director
role: STUDY_DIRECTOR
References: