Open-label, 2-arm, multicenter clinical trial to assess safety, efficacy and PK/PD of MOR202 in anti-PLA2R antibody positive membranous nephropathy (aMN)
- Conditions
- Anti-PLA2R antibody positive membranous nephropathy (aMN)MedDRA version: 21.1Level: LLTClassification code 10027170Term: Membranous nephropathySystem Organ Class: 100000004857Therapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2020-002985-15-GB
- Lead Sponsor
- MorphoSys AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 22
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.
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
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. Serologic or virologic markers positive for HIV, hepatitis C (subjects with positive anti hepatitis C virus [anti-HCV] antibody but negative HCV RNA polymerase chain reaction [PCR] may enroll) or active or latent hepatitis B (subjects with positive hepatitis B surface antigen [HBsAg] are excluded, subjects with isolated positive hepatitis B core antibody [anti-HBc] but non-detectable hepatitis B virus (HBV) DNA by PCR may enroll).
18. For any other preexisting symptoms and impairments of health or any residual toxicity from prior therapy classified = grade 3 (NCI-CTCAE): these subjects may be included upon confirmation by the Medical Monitor.
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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the efficacy of 2 different dosing regimens of MOR202 in subjects with anti PLA2R antibody positive MN ;Secondary Objective: • To assess the efficacy of 2 different dosing regimens of MOR202<br>• To assess the safety of MOR202 <br>• To assess the PK profile of MOR202<br>• To investigate the potential immunogenicity of MOR202<br>;Primary end point(s): Percent change of anti-PLA2R antibody levels;Timepoint(s) of evaluation of this end point: 3 months compared to baseline
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • Immunological complete response (ICR) rate<br>• Overall proteinuria response (OPR) rate<br>• Frequency, incidence and severity of TEAEs.<br>• Serum concentrations of MOR202 over time.<br>• Formation of anti drug antibodies.<br>;Timepoint(s) of evaluation of this end point: ICR: 3 months, 6 months, 12 months and 24 months<br>OPR: 6 months, 12 months and 24 months<br>Other time points are according to the Schedule of Activities in the study protocol