Open Label Clinical Trial to assess Safety and Efficacy of MOR202 in Membranous Nephropathy
- Conditions
- Primary (anti-PLA2R antibody positive) Membranous NephropathyMedDRA version: 21.1Level: LLTClassification code 10027170Term: Membranous nephropathySystem Organ Class: 100000004857Therapeutic area: Body processes [G] - Immune system processes [G12]
- Registration Number
- EUCTR2019-000780-24-IT
- 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
- 30
1. =18 to =80 years (at date of signing ICF)
2. Urine protein to creatinine ratio (UPCR) of = 3.0 g/g (as measured from a 24 hour urine collection)
3. MN diagnosed on the basis of a biopsy, archival biopsy acquired within 5 years prior to screening is acceptable.
4. Estimated glomerular filtration rate (eGFR) =50 ml/min/1.73m² or >30 and <50 ml/min/1.73m², and IFTA (interstitial fibrosis and tub-ular atrophy) score of less than 25% on a renal biopsy obtained within the last 6 months prior to start of screening. If a subject falls into the latter range without availability of an adequate biopsy, a biopsy at screening should be performed for IFTA assessment.
5. The subject is on supportive treatment with an ACEI or an ARB for at least 4 weeks prior to screening. The ACEI or ARB treatment should have reached a stable dose according to best local practice.
6. Systolic BP = 150 mmHg and diastolic BP = 100 mmHg after a period of 5 minutes of rest as measured at screening
7. Subject vaccinated against Pneumococcus within the last 3 years prior to date of signing ICF (subjects may be vaccinated during screening to meet this criterion; interval to first dose of MOR202 must be at least 14 days (1)).
8. Cohort 1: Serum anti-PLA2R antibodies = 150.0 RU/mL as determined at screening by Euroimmun ELISA
9. Cohort 1: Serum anti-PLA2R antibodies before screening ris-ing or stable as judged by the investigator
10. Cohort 1, relapse subjects only: Must have had complete remission of proteinuria, or a combination of partial remission of proteinuria (demonstrating at least 50 % decrease) with a remission of serum anti-PLA2R anti-body titer to less than 20.0 RU/mL (Euroimmun ELISA) or negative Immunfluorescence Test (IFT). Remission must have lasted for at least 6 months according to clinical judgement.
11. Cohort 2: Failure of previous therapy, i.e. subject never achieved a reduction of serum anti-PLA2R antibody titers to below 20.0 RU/ml (Euroimmun ELISA) during or after completion of a recognized IST contain-ing CSA, tacrolimus, MMF, ACTH or alkylating agents (e.g. cy-clophosphamide), or RTX determined after at least 6 months after start of this IST.
12. Cohort 2: Subjects may have received a maximum of two prior treatment lines of immunosuppressive therapy (retreatment for re-lapse with the same regimen is considered a line of its own). A planned, fixed sequence of different therapeutic agents (e. g. STARMEN regimen) is considered as one regimen.
13. Female of non-childbearing potential fulfilling one of the criteria:
a. post-menopausal: after 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms)
b. surgically sterile: tubal ligation at least 6 weeks before taking trial treatment, hysterectomy, or bilateral oophorectomy
c. genetically sterile: e. g. Turner syndrome, uterine agenesis.
14. Sexually active females of reproductive potential should use one of the following contraception options until 3 months after the last dose of MOR202:
a. One method of contraception that has a typical use failure rate of <1% (i.e., less than 1 pregnancy expected per 100 women), which would include
sterilization surgery for women, sterilization implant for women, sterilization surgery for men, Copper IUD, IUD with progestin, or implantable rod
b. A hormonal method of contraception (i.e., shot/injection, oral contraceptive, contraceptive patch, vaginal contraceptive ring, havin
1. Hemoglobin < 90 g/L
2. Thrombocytopenia: Platelets < 100.0x10^9/L
3. Neutropenia: Neutrophils < 1.5x10^9/L
4. Leukopenia: Leukocytes < 3.0x10^9/L
5. Hypogammaglobulinemia: Serum immunoglobulins =5.0 g/L
6. Secondary cause of MN (e.g. SLE, medications, malignancies) as determined by the investigator
7. Concomitant renal disease other than MN (e.g., diabetic renal disease, lupus nephritis, 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 membranous nephropathy without histological signs of diabetic nephropathy and their disease is controlled, such as:
o Hba1c <8.0 % or 64 mmol/mol,
o No diabetic retinopathy known
o No peripheral neuropathy known
10. Previous treatment with an anti-CD38 antibody
Note: Cohort 1 specific criteria are not applicable in France
11. Cohort 1 newly diagnosed subjects only: previous treatment for MN with alkylating agents, RTX, cyclosporine, tacrolimus, MMF, all with or without corticosteroids
12. Cohort 1 relapse subjects and Cohort 2: Treatment within 3 months prior to screening with alkylating agents, RTX, CSA, tacrolimus, MMF, all with or without corticoster-oids
13. Significant uncontrolled cardiovascular disease or cardiac insufficiency (New York Heart Association [NYHA] class IV) as judged by the investigator
14. Clinically relevant findings on a 12 lead ECG as determined by the investigator at screening
15. History of significant cerebrovascular disease or sensory or motor neuropathy of tox-icity = grade 3
16. Total bilirubin, aspartate aminotransferase and alanine aminotransferase >1.5 x ULN, alkaline phosphatase >2.0 x ULN
17. Treatment within five terminal half-lives (if known) or within the last 30 days prior to baseline (whatever is longer) with investigational drugs.
18. Known or suspected hypersensitivity to MOR202 and its excipients (L-histidine, su-crose, polysorbate 20)
19. Serologic or virologic markers positive for active or latent hepatitis B, C, or HIV at screening (central lab, HBsAg positive subjects are not eligible; HBcAb positive sub-jects are only eligible, if HBsAb is positive as well)
20. For any other preexisting symptoms and impairments of health classified or any re-sidual toxicity from prior therapy = grade 3 (NCI-CTCAE, see 3.2): these subjects may be included upon confirmation by the medical department of the sponsor
21. Pregnancy or breast feeding
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 safety and tolerability of MOR202 treatment in subjects with anti-PLA2R antibody positive membranous nephropathy (aMN);Secondary Objective: To assess the effect of MOR202 on serum anti-PLA2R antibodies in subjects with aMN<br>To assess immunogenicity of MOR202 (anti-MOR202 antibody formation)<br>To assess the pharmacokinetic (PK) profile of MOR202<br>To assess safety in the follow-up phase;Primary end point(s): Incidence and severity of treatment-emergent adverse events (TEAE);Timepoint(s) of evaluation of this end point: Throughout the study
- Secondary Outcome Measures
Name Time Method Secondary end point(s): KEY SECONDARY ENDPOINT: Best Immunological Response: rate of sICR, ICR and IPR based on re-duction of serum anti-PLA2R antibody titer <br>SECONDARY ENDPOINTS: <br>1. Number and antibody titers of subjects tested positive for anti-MOR202 antibodies <br>2. MOR202 serum concentrations after multiple i.v. administrations <br>3. Incidence and severity of AEs in the follow-up phase;Timepoint(s) of evaluation of this end point: Throughout the study