Back to resultsEfficacy, Safety and PK/PD of MOR202 in Anti-PLA2R + Membranous Nephropathy (aMN) (NewPLACE) (NewPLACE)
Primary Purpose
Glomerulonephritis, Membranous Nephropathy, antiPLA2R Positive
Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
MOR202
Sponsored by
About this trial
This is an interventional treatment trial for Glomerulonephritis
Eligibility Criteria
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:
- Not a female of childbearing potential (FCBP)
- 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:
- Glycated hemoglobin (HbAlc) <8.0 % or 64 mmol/mol.
- No diabetic retinopathy known.
- No peripheral neuropathy known.
- Total bilirubin, aspartate aminotransferase or alanine aminotransferase >1.5 x ULN, alkaline phosphatase >3.0 x ULN.
Sites / Locations
- Managadze National Center of Urology
- Tbilisi State Medical University and Ingorokva High Medical Technology University Clinic
- University Hospital Aachen
- Charite
- DaVita Clinical Research
- Uniklinikum
- Hospital of Johannes Gutenberg University
- General Hospital of Athens
- General Hospital of Heraklion Venizeleio-Papaneio
- University General Hospital of Patras
- General Hospital of Thessaloniki
- Hallym University Sacred Heart Hospital
- JeJu National University Hospital
- Konkuk University Hospital
- Kyung Hee University Hospital at Gangdong
- Seoul National University Bundang Hospital
- Botkin Hospital Moscow
- First Pavlov State Medical University of St. Petersburg
- Chang Gun Kaog Memorial Hospital
- Shuang Ho Hospital
- China Medical University Hospital
- Taichung Veterans General Hospital
- National Taiwan University Hospital
- Kings College
- Nottingham Renal and Transplant Unit
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
MOR202 Arm 1
MOR202 Arm 2
Arm Description
5 doses administered on Day 1, 8, 15, 29, and 57
2 doses administered on Day 1 and 15
Outcomes
Primary Outcome Measures
efficacy: percent change of anti-PLA2R antibody levels
efficacy of 2 different dosing regimens of MOR202 in subjects with anti-PLA2R antibody positive MN
Secondary Outcome Measures
efficacy: immunological complete response (ICR) rate
efficacy of 2 different dosing regimens of MOR202
efficacy: overall proteinuria response (OPR) rate
efficacy of 2 different dosing regimens of MOR202
safety: determined by the frequency, incidence and severity of TEAEs
frequency, incidence and severity of treatment-emergent adverse events
PK profile
MOR202 serum concentrations after multiple i.v. administrations
immunogenicity
number of subjects developing anti-MOR202 antibodies
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04733040
Brief Title
Efficacy, Safety and PK/PD of MOR202 in Anti-PLA2R + Membranous Nephropathy (aMN) (NewPLACE)
Acronym
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)
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 20, 2021 (Actual)
Primary Completion Date
January 11, 2024 (Anticipated)
Study Completion Date
January 11, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
HI-Bio
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief 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
Detailed 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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glomerulonephritis, Membranous Nephropathy, antiPLA2R Positive
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
MOR202 Arm 1
Arm Type
Experimental
Arm Description
5 doses administered on Day 1, 8, 15, 29, and 57
Arm Title
MOR202 Arm 2
Arm Type
Experimental
Arm Description
2 doses administered on Day 1 and 15
Intervention Type
Drug
Intervention Name(s)
MOR202
Intervention Description
5 or 2 doses of MOR202 will be administered as an intravenous infusion
Primary Outcome Measure Information:
Title
efficacy: percent change of anti-PLA2R antibody levels
Description
efficacy of 2 different dosing regimens of MOR202 in subjects with anti-PLA2R antibody positive MN
Time Frame
3 months compared to baseline
Secondary Outcome Measure Information:
Title
efficacy: immunological complete response (ICR) rate
Description
efficacy of 2 different dosing regimens of MOR202
Time Frame
ICR rate at 3 months, 6 months, 12 months and 24 months
Title
efficacy: overall proteinuria response (OPR) rate
Description
efficacy of 2 different dosing regimens of MOR202
Time Frame
OPR rate at 6 months, 12 months and 24 months.
Title
safety: determined by the frequency, incidence and severity of TEAEs
Description
frequency, incidence and severity of treatment-emergent adverse events
Time Frame
through treatment completion, an average of 3 months per treatment period
Title
PK profile
Description
MOR202 serum concentrations after multiple i.v. administrations
Time Frame
through study completion, an average of 1 year
Title
immunogenicity
Description
number of subjects developing anti-MOR202 antibodies
Time Frame
through study completion, an average of 1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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:
Not a female of childbearing potential (FCBP)
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:
Glycated hemoglobin (HbAlc) <8.0 % or 64 mmol/mol.
No diabetic retinopathy known.
No peripheral neuropathy known.
Total bilirubin, aspartate aminotransferase or alanine aminotransferase >1.5 x ULN, alkaline phosphatase >3.0 x ULN.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
HI-Bio Clinical Program Lead
Organizational Affiliation
HI-Bio
Official's Role
Study Director
Facility Information:
Facility Name
Managadze National Center of Urology
City
Tbilisi
Country
Georgia
Facility Name
Tbilisi State Medical University and Ingorokva High Medical Technology University Clinic
City
Tbilisi
Country
Georgia
Facility Name
University Hospital Aachen
City
Aachen
Country
Germany
Facility Name
Charite
City
Berlin
Country
Germany
Facility Name
DaVita Clinical Research
City
Düsseldorf
Country
Germany
Facility Name
Uniklinikum
City
Essen
Country
Germany
Facility Name
Hospital of Johannes Gutenberg University
City
Mainz
Country
Germany
Facility Name
General Hospital of Athens
City
Athens
Country
Greece
Facility Name
General Hospital of Heraklion Venizeleio-Papaneio
City
Heraklion
Country
Greece
Facility Name
University General Hospital of Patras
City
Patras
Country
Greece
Facility Name
General Hospital of Thessaloniki
City
Thessaloníki
Country
Greece
Facility Name
Hallym University Sacred Heart Hospital
City
Chuncheon
Country
Korea, Republic of
Facility Name
JeJu National University Hospital
City
Jeju
Country
Korea, Republic of
Facility Name
Konkuk University Hospital
City
Seoul
Country
Korea, Republic of
Facility Name
Kyung Hee University Hospital at Gangdong
City
Seoul
Country
Korea, Republic of
Facility Name
Seoul National University Bundang Hospital
City
Seoul
Country
Korea, Republic of
Facility Name
Botkin Hospital Moscow
City
Moscow
Country
Russian Federation
Facility Name
First Pavlov State Medical University of St. Petersburg
City
Saint Petersburg
Country
Russian Federation
Facility Name
Chang Gun Kaog Memorial Hospital
City
Kaohsiung
Country
Taiwan
Facility Name
Shuang Ho Hospital
City
New Taipei City
Country
Taiwan
Facility Name
China Medical University Hospital
City
Taichung
Country
Taiwan
Facility Name
Taichung Veterans General Hospital
City
Taichung
Country
Taiwan
Facility Name
National Taiwan University Hospital
City
Taipei
Country
Taiwan
Facility Name
Kings College
City
London
Country
United Kingdom
Facility Name
Nottingham Renal and Transplant Unit
City
Nottingham
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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.
Learn more about this trial
Efficacy, Safety and PK/PD of MOR202 in Anti-PLA2R + Membranous Nephropathy (aMN) (NewPLACE)
We'll reach out to this number within 24 hrs