MOR202 for refractory M

Phase 1

• Conditions: Membranous Nephropathy who Failed Anti-CD20 Target Therapy.; MedDRA version: 21.1Level: LLTClassification code 10027170Term: Membranous nephropathySystem Organ Class: 100000004857; Therapeutic area: Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13]

• Registration Number: EUCTR2021-000835-30-IT
• Lead Sponsor: IRCCS- ISTITUTO DI RICERCHE FARMACOLOGICHE MARIO NEGRI

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-08-30
• Last Update Posted: 2 March 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

- Age =18 years.
- Biopsy-proven membranous nephropathy with or without detectable circulating anti-PLA2R or anti-THSD7A antibodies.
- Background treatment with RAS blocking agents (ACE inhibitor and/or ARBs), at maximum tolerated doses and adequately controlled blood pressure (BP <140/90 mmHg in at least three consecutive readings at screening).
- One condition between:
•Anti-CD20 Resistance: residual proteinuria =3.5 g/day (mean of three consecutive 24-hour urine collections), with less than 50% reduction compared to pre-treatment values at least 12 months after anti-CD20 antibody therapy.
•Anti-CD20 Dependence: frequently relapsing NS (nephrotic-range proteinuria for >50% of time in the last five years or since disease onset, whichever is shorter) despite repeated treatments with anti-CD20 antibodies.
- Estimated GFR >30 ml/min/1.73m2 (CKD-EPI equation) and less than 50% of sclerotic glomeruli in patients receiving renal biopsy.
- A minimum 12-month wash-out from last anti-CD20 therapy with rituximab and/or other monoclonal antibodies.
- No immunosuppressive therapy with steroid, cyclophosphamide, cyclosporine, mycophenolate mofetil or any other immunosuppressant over the last 6 months; in case of therapies administered for less than 2 weeks, no washout time will be required prior to inclusion.
- Completed anti SARS Cov 2 Vaccination
- Written informed consent
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 5
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion Criteria

- Clinically relevant neutropenia (neutrophils < 1.5 x 109/L), anemia (Hb levels <9.0 g/dL), thrombocytopenia (platelet count < 150.000/mm3), hypogammaglobulinemia (serum immunoglobulin =5.0 g/L), increased liver transaminase or bilirubin levels (total bilirubin, aspartate aminotransferase or alanine aminotransferase >1.5 x ULN, alkaline phosphatase >3.0 x ULN).
- Significant uncontrolled cardiovascular disease (including arterial or venous thrombotic or embolic events over the last three months) or cardiac insufficiency (New York Heart Association [NYHA] class IV) as judged by the investigator.
- Clinically relevant findings on a 12-lead electrocardiogram (ECG) as determined by the investigator at screening.
- History of significant cerebrovascular disease (stroke or transitory ischemic attack over the last three months) or sensory or motor neuropathy of toxicity = grade 3.
- Any clinical condition that in the investigator judgment could affect the possibility to complete the study or could have a major confounding effect on study findings and data interpretation.
- Known intolerance to the study drug or its excipients
- Any viral, bacterial or fungal infection without complete symptoms resolution from at least two weeks.
- Serologic or virologic markers positive for HIV, hepatitis C (patients with positive antihepatitis C virus [anti-HCV] antibody but negative HCV RNA polymerase chain reaction [PCR] can enroll) or active or latent hepatitis B (patients with positive hepatitis B surface antigen [HBsAg] are excluded). Patients with isolated positive hepatitis B core antibody [anti-HBc], hepatitis B virus (HBV) DNA test by PCR must be non-detectable to enroll.
- History of malignancy within the prior 5 years.
- Participation in other clinical trials within 4 weeks of signing the consent form.
- Expected need of anti SARS Cov 2 vaccination during the study period
- Pregnancy or breast-feeding.
- Childbearing potential in males and females non using an highly effective method of contraception according to 2020 CTFG Recommendations related to contraception and pregnancy testing in clinical trials (https://www.hma.eu/fileadmin/dateien/Human_Medicines/01-About_HMA/Working_Groups/CTFG/2020_09_HMA_CTFG_Contraception_guidance_Version_1.1_updated.pdf).
- Legal incapacity or limited legal capacity.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified