Open-label, 2-arm, multicenter clinical trial to assess safety, efficacy and PK/PD of MOR202 in anti-PLA2R antibody positive membranous nephropathy (aMN)

• Register: EUCTR
• Last refreshed on: 15 January 2024
• Main ID: EUCTR2020-002985-15-GR
• Date of registration: 11/09/2020
• Prospective Registration: Yes
• Primary sponsor: Human Immunology Biosciences, Inc.
• Public title: Open-label, 2-arm, multicenter clinical trial to assess safety, efficacy and PK/PD of MOR202 in anti-PLA2R antibody positive membranous nephropathy (aMN)
• Scientific 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) - NewPLACE
• Date of first enrolment: 22/10/2020
• Target sample size: 22
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-002985-15
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Different dosing regimen Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

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

Contacts

• Name: Clinical Trial Information
• Affiliation: Human Immunology Biosciences, Inc.

• Name: Clinical Trial Information
• Affiliation: Human Immunology Biosciences, Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Subjects = 18 to = 80 years (at date of signing the informed consent form [ICF]).
2. Urine protein to creatinine ratio (UPCR) of = 3.0 g/g (as determined by a 24 h urine collection) or proteinuria = 3.5 g/24 h (as determined by a 24 h urine collection)
3. Anti-PLA2R antibody positive MN in need for IST according to the investigator’s judgment. The diagnosis of MN should be histologically documented with a diagnostic biopsy; for this purpose, a biopsy at screening or an archival biopsy acquired within 5 years prior to screening is acceptable.
4. Estimated glomerular filtration rate (eGFR) = 50 ml/min/1.73 m².
Alternatively, subjects with an 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 is histologically documented; for this purpose, a biopsy at screening or an archival biopsy acquired within 6 months prior to start of screening is needed.
5. 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.
6. Systolic blood pressure (BP) = 150 mmHg and diastolic BP = 100 mmHg after 5 minutes of rest.
7. Serum anti-PLA2R antibodies = 50.0 RU/mL determined by Euroimmun ELISA.
8. Female subjects: A female is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
a. Not a female of childbearing potential (FCBP) ; OR
b. 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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 7

Exclusion criteria:
1. Hemoglobin < 80 g/L (4.9 mmol/L).
2. Thrombocytopenia: Platelets < 100.0 x 10^9/L.
3. Neutropenia: Neutrophils < 1.5 x 10^9/L.
4. Leukopenia: Leukocytes < 3.0 x 10^9/L.
5. B-cells < 5 x 10^6/L
6. Secondary cause of MN (e.g. malignancies, medications, systemic lupus erythematosus).
7. Concomitant renal disease other than MN (e.g., diabetic renal disease, lupus nephritis, immunoglobulin A (IgA) nephropathy).
8. Diabetes mellitus type 1.
9. 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:
a. Glycated hemoglobin (HbA1c) <8.0 % or 64 mmol/mol.
b. No diabetic retinopathy known.
c. No peripheral neuropathy known.
10. Previous treatment with an anti-CD38 antibody.
11. Prior to screening start, oral or parenteral treatment with:
a. Mycophenolate mofetil (MMF) or high dose corticosteroids (> 20 mg prednisone/day) within 30 days prior to start of screening.
b. Alkylating agents (e.g. cyclophosphamide) or calcineurin inhibitors (CNIs) (e.g. tacrolimus, cyclosporine A) within 90 days.
c. Biologic drugs including rituximab (RTX) within 180 days.
d. Any other oral/parenteral IST within 180 days.
12. Significant uncontrolled cardiovascular disease or cardiac insufficiency (New York Heart Association [NYHA] class IV) as judged by the investigator.
13. Clinically relevant findings on a 12-lead electrocardiogram (ECG) as determined by the investigator at screening.
14. History of significant cerebrovascular disease or sensory or motor neuropathy of toxicity = grade 3.
15. Total bilirubin, aspartate aminotransferase or alanine aminotransferase >1.5 x ULN, alkaline phosphatase >3.0 x ULN.
16. Known or suspected hypersensitivity to MOR202 and its excipients (L-histidine, sucrose, polysorbate 20).
17. All patients will be screened for HIV, HBsAg, HBsAb, HBcAb, HC Ab and Hepatitis C RNA. If a patient tests positive for any of the following: HIV, HBsAg, HBcAb or HC Ab or Hepatitis C RNA, then the patient should be excluded from the study. If a patient tests positive only for HBsAb,
HBV-DNA should be tested and if this test result is positive the patient should be excluded from the study. Patients who test positive only for HBsAb and negative for HBV-DNA are eligible.
18. For any other pre-existing symptoms and impairments of health or any residual toxicity from prior therapy classified = grade 3 (NCI-CTCAE)
19. Any malignancy within 5 years prior to screening start, with the exception of adequately treated in situ carcinoma of the cervix uteri, basal or squamous cell carcinoma or non melanomatous skin cancer.
20. Treatment within 5 terminal half-lives (if known) or within the last
30 days prior to baseline (whatever is longer) with investigational drugs.
21. Any active infection (viral, fungal, bacterial) requiring systemic therapy.
22. Any other disease which, in the investigator's opinion, is likely to compromise the subject's ability to participate in the trial.
23. Not applicable to EU sites.
24. Individuals housed in institutions due to official or judicial orders or who are in positions of dependency vis-à-vis the sponsor or investigator are not eligible for participation.
25. History or current hemostasis or bleeding disorder.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Anti-PLA2R antibody positive membranous nephropathy (aMN)
MedDRA version: 21.1 Level: LLT Classification code 10027170 Term: Membranous nephropathy System Organ Class: 100000004857

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Name: MOR202
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: not yet assigned
CAS Number: 2197112-39-1
Current Sponsor code: MOR202
Other descriptive name: MOR03087
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 65-

Primary Outcome(s)

Main Objective: To assess the efficacy of 2 different dosing regimens of MOR202 in subjects with anti PLA2R antibody positive MN

Primary end point(s): Percent change of anti-PLA2R antibody levels

Secondary Objective: • To assess the efficacy of 2 different dosing regimens of MOR202
• To assess the safety of MOR202
• To assess the PK profile of MOR202
• To investigate the potential immunogenicity of MOR202

Timepoint(s) of evaluation of this end point: 3 months compared to baseline

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: ICR: 3 months, 6 months, 12 months and 24 months
OPR: 6 months, 12 months and 24 months
Other time points are according to the Schedule of Activities in the study protocol

Secondary end point(s): • Immunological complete response (ICR) rate
• Overall proteinuria response (OPR) rate
• Frequency, incidence and severity of treatment-emergent adverse events (TEAEs).
• Serum concentrations of MOR202 over time.
• Formation of anti drug antibodies.

Secondary ID(s)

MOR202C205

2020-002985-15-GB

Source(s) of Monetary Support

Human Immunology Biosciences, Inc.

Ethics review

Status: Approved
Approval date: 16/10/2020
Contact: