Trial to Assess Safety and Efficacy of MOR202 in Anti-PLA2R + Membranous Nephropathy (aMN)
- Registration Number
- NCT04145440
- Lead Sponsor
- HI-Bio, A Biogen Company
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 31
- > 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Cohort 2 (refractory participants) MOR202 Participants with membranous nephropathy refractory to immunosuppressive treatment received MOR202 as an intravenous infusion over 6 treatment cycles of 28-days each. Dosing occurred weekly in Cycle 1 and every 4 weeks in Cycles 2 to 6. Cohort 1 (newly diagnosed or relapsed participants) MOR202 Participants with newly diagnosed or relapsed membranous nephropathy received MOR202 as an intravenous infusion over 6 treatment cycles of 28-days each. Dosing occurred weekly in Cycle 1 and every 4 weeks in Cycles 2 to 6.
- Primary Outcome Measures
Name Time Method Number of Participants With Adverse Events Week 1 to Week 24 An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Percentage of Participants With Adverse Events Week 1 to Week 24 An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
- Secondary Outcome Measures
Name Time Method Percentage of Participants Tested Positive for Anti-felzartamab Antibodies Baseline; Up to 52 weeks Antibody Titers of Participants Tested Positive for Anti-felzartamab Antibodies Baseline; Up to 52 weeks Best Immunological Response Rate (BIRR) Up to 52 weeks The BIRR was defined as the percentage of participants with a best immunological response of stringent immunological complete response (sICR), immunological complete response (ICR), or immunological partial response (IPR) prior to the start of prohibited treatment or progression, based on reduction of serum anti-PLA2R antibody titer.
Number of Participants Tested Positive for Anti-felzartamab Antibodies Baseline; Up to 52 weeks Felzartamab Serum Concentrations After Multiple Intravenous Administrations 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) Number of Participants With AEs During the Follow-up Period Week 25 to Week 52 An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Percentage of Participants With AEs During the Follow-up Period Week 25 to Week 52 An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Trial Locations
- Locations (45)
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
🇺🇸Torrance, California, United States
Northwest Louisiana Nephrology Research
🇺🇸Shreveport, Louisiana, United States
Radboud UMC Niimegen Nephrology
🇳🇱Nijmegen, Netherlands
University of Miami Division of Nephrology & Hypertension
🇺🇸Miami, Florida, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
North America Research Institute
🇺🇸Azusa, California, United States
GA Nephrology Associates
🇺🇸Lawrenceville, Georgia, United States
MedResearch, Inc
🇺🇸El Paso, Texas, United States
Texas Research Institute
🇺🇸Fort Worth, Texas, United States
O.L.V. Ziekenhuis
🇧🇪Aalst, Belgium
St. George Hospital
🇦🇺Sydney, New South Wales, Australia
Royal Melbourne Hospital
🇦🇺Melbourne, Victoria, Australia
Western Health
🇦🇺Melbourne, Australia
C.H.U. Brugmann - Site Victor Horta
🇧🇪Brussels, Belgium
Universitair Ziekenhuis Brussels
🇧🇪Brussels, Belgium
Azienda Ospedaliera Universitaria Careggi
🇮🇹Firenze, Italy
UZ Leuven
🇧🇪Leuven, Belgium
Ospedale San Raffaele
🇮🇹Milan, Italy
CHU Saint Etienne - Hôpital Nord
🇫🇷Saint-Priest-en-Jarez, France
CHU de Grenoble - Hôpital Albert Michallon
🇫🇷Grenoble, France
Cliniques Universitaires Saint-Luc
🇧🇪Bruxelles, Belgium
Hopital Tenon Service de nephrologie
🇫🇷Paris, France
Hopital Claude Huriez -CHU Lille
🇫🇷Lille, France
CHU de Liège
🇧🇪Liège, Belgium
Groupe Hospitalier Pellegrin - Hôpital Pellegrin
🇫🇷Bordeaux, France
Miedzyleski Szpital Specjalistyczny
🇵🇱Warsaw, Poland
Ospedale Borgo Roma
🇮🇹Verona, Italy
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Centrum Zdrowia MDM
🇵🇱Warsaw, Poland
SPZOZ Centralny Szpital Kliniczny UM w Lodzi
🇵🇱Łódź, Poland
Hallym University Kangdong Sacred Heart Hospital
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital Universitario Puerta de Hierro Majadahonda
🇪🇸Madrid, Spain
Hospital Universitario Reina Sofia
🇪🇸Córdoba, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario Dr. Peset
🇪🇸Valencia, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Hospital General Universitario de Valencia
🇪🇸Valencia, Spain
The Ohio State University Wexner Medical Center
🇺🇸Columbus, Ohio, United States
UCSF Medical Center
🇺🇸San Francisco, California, United States
Chungnam National University Hospital
🇰🇷Daejeon, Korea, Republic of
Kidney Care and Transplant Services of New England, PC
🇺🇸Springfield, Massachusetts, United States
Gangnam Severance Hospital
🇰🇷Seoul, Korea, Republic of