EUCTR2019-000780-24-IT进行中（未招募）1 期
A Phase Ib/IIa, Open-Label, Multicenter Clinical Trial to Assess Safety and Efficacy of the Human Anti-CD38 Antibody MOR202 in anti-PLA2R antibody positive Membranous Nephropathy (aMN) - M-PLACE
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- MorphoSys AG
- 入组人数
- 30
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional clinical trial of medicinal product
入排标准
- 性别
- All
入选标准
- •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
排除标准
- •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
研究者
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