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-PL
- 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 informed consent form (ICF).
2. Urine protein to creatinine ratio (UPCR) of = 3.0000 g/g OR proteinuria = 3.500g/24 h from 24-h urine at screening.
3. Anti-PLA2R antibody positive MN in need for IST according to investigator's judgement. 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 screening is acceptable.
4.Estimated glomerular filtration rate (eGFR) = 50 mL/min/1.73m². Alternatively eGFR =30 and <50 mL/min/1.73m² and interstitial fibrosis and tubular atrophy (IFTA) score < 25% in a renal biopsy obtained within the last 6 months prior to start of screening (if not available, a biopsy should be performed at screening to obtain the IFTA assessment).
5. Not in spontaneous remission despite proper treatment with ACEIs, ARBs (sufficient dose and treatment duration) as per clinical practice and guidelines. If the PI determines that a subject is intolerant to an ACEI or ARB, the reason must be documented and approval obtained from the Medical Monitor prior to enrolment.
6. Systolic BP = 150 mmHg and diastolic BP = 100 mmHg after a period of 5 minutes rest.
7. Subject vaccinated against Pneumococcus within the last 5 years prior to date of signing ICF (subjects may be vaccinated during screening to meet this criterion during screening; interval to first dose of MOR202 must be at least 14 days [MSD SmPC]).
8. Cohort 1 comprises newly or relapsed subjects: Serum anti-PLA2R antibodies =50.0 RU/ml determined by Euroimmun ELISA at central laboratory.
9. Cohort 2 comprises therapy refractory subjects:
a. subject did not achieve immunological remission after prior IST(s) as documented by the investigator AND
b. subject is without promising standard therapeutic options as documented by the investigator(i.e. investigator expects efficacy or safety issues with remaining IST options AND
c. serum anti-PLA2R antibodies =20RU/mL measured at screening by the Euroimmun ELISA at central laboratory
10. 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.
11. 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 intra-uterine device (IUD), IUD with progestin, or implantable rod
b. A hormonal method of contraception (i.e., shot/injection, oral contraceptive, contraceptive patch, vaginal contraceptive ring, having typical use failure rate = 9%) plus a barrier method (i.e., diaphragm with spermicide, sponge with spermicide, cervical cap with spermicide, male condom, female condom, spermicide alone).
Note: France will only enroll patients in Cohort 2.
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
1.Hemoglobin < 80 g/L
2.Thrombocytopenia: Platelets < 100.0 × 109/L
3.Neutropenia: Neutrophils < 1.5 × 109/L
4.Leukopenia: Leukocytes < 3.0 × 109/L
5.Hypogammaglobulinemia defined as serum immunoglobulin = 4.0 g/L
6.B-cells < 5 × 106/L.
7.Secondary cause of MN (e.g. SLE, medications, malignancies) as determined by the investigator.
8.Concomitant renal disease other than MN (e.g., diabetic renal disease, lupus nephritis, IgA nephropathy).
9.Diabetes mellitus type 1.
10.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 their disease is controlled, such as:
•Hba1c < 8.0 % or 64 mmol/mol
•No diabetic retinopathy known
•No peripheral neuropathy known
11.Previous treatment with an anti-CD38 antibody.
12.Subject received treatment with:
a.Mycophenolate mofetil (MMF) or high dose corticosteroids (> 20 mg prednisone/day), within 30 days prior to screening OR
b.Alkylating agents (e.g. cyclophosphamide [CYC]) or CNIs (e.g. tacrolimus, cyclosporine A [CSA]) within 90 days OR
c.Biologic drugs including RTX within 180 days
d.Any other oral/parenteral IST within 180 days.
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 toxicity = grade 3.
16.Total bilirubin, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) > 1.5 × ULN, alkaline phosphatase (ALP) > 2.0×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, sucrose, polysorbate 20).
19.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 be enrolled).
20.For any other pre-existing symptoms and impairments of health classified or any residual toxicity from prior therapy = grade 3 (NCI-CTCAE, see Section 3.2): these subjects may be included upon confirmation by the medical department of the sponsor.
21.Pregnancy or breast feeding.
22.Any active infection (viral, fungal, bacterial) requiring systemic therapy.
23.Any malignancy within 5 years prior to date of screening, with the exception of adequately treated in situ carcinoma of the cervix, uteri, basal or squamous cell carcinoma or non-melanomatous skin cancer.
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 the safety in subjects with aMN after MOR202 treatment and during 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 Timepoint(s) of evaluation of this end point: Throughout the study ;Secondary end point(s): KEY SECONDARY ENDPOINT: Best Immunological Response: rate of stringent immunological complete response (sICR), immunological complete response (ICR) and immunological partial response (IPR) based on reduction 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