Clinical trial NCT04733040: Efficacy, Safety and PK/PD of MOR202 in Anti-PLA2R+ Membranous Nephropathy (aMN) (NewPLACE)
Official title: A Phase IIa, Open-Label, 2-Arm Multicenter Clinical Trial to Evaluate the Efficacy, Safety and PK/PD of the Human Anti-CD38 Antibody MOR202 in Anti-PLA2R Antibody Positive Membranous Nephropathy (NewPLACE)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Glomerulonephritis
Membranous Nephropathy
antiPLA2R Positive
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2021-02-01
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This 2-arm, multi-center, open-label, parallel-group phase II trial will assess the efficacy, safety and pharmacokinetics/pharmacodynamics of the human antibody MOR202 in subjects with anti-PLA2R antibody-positive membranous nephropathy indicated for immunosuppressive therapy

Detailed description: After treatment, subjects will enter a repeat treatment period (3 months) if necessary; and a final follow-up period of 15 to 18 months.

Study Sponsor, originally HI-Bio, Inc., is now HI-Bio, A Biogen Company.

Eligibility criteria: Inclusion Criteria:

* Subjects ≥ 18 to ≤ 80 years (at date of signing the informed consent form \[ICF\]).
* Urine protein to creatinine ratio (UPCR) of ≥ 3.0 g/g or proteinuria ≥ 3.5 g/24 h
* Estimated glomerular filtration rate (eGFR) ≥ 50 ml/min/1.73 m² (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)
* 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. If the subject is intolerant to ACEI and ARBs, the reason must be documented and approval for enrollment be obtained from the Medical Monitor.
* Systolic blood pressure (BP) ≤150 mmHg and diastolic BP ≤100 mmHg after 5 minutes of rest.
* Serum anti-PLA2R antibodies ≥ 50.0 RU/mL determined by Euroimmun ELISA.
* Female subjects: A female is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:

  1. Not a female of childbearing potential (FCBP)
  2. 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

Key Exclusion Criteria:

* Hemoglobin \< 80 g/L.
* Thrombocytopenia: Platelets \< 100.0 x 10\^9/L.
* Neutropenia: Neutrophils \< 1.5 x 10\^9/L.
* Leukopenia: Leukocytes \< 3.0 x 10\^9/L.
* Hypogammaglobulinemia: Serum immunoglobulins ≤ 4.0 g/L.

Subjects may receive supportive therapies to meet the above criteria

* B-cells \< 5 x 10\^6/L
* 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:

  1. Glycated hemoglobin (HbA1c) \<8.0 % or 64 mmol/mol.
  2. No diabetic retinopathy known.
  3. No peripheral neuropathy known.
* Total bilirubin, aspartate aminotransferase or alanine aminotransferase \>1.5 x ULN, alkaline phosphatase \>3.0 x ULN.

Primary outcomes:
measure: efficacy: percent change of anti-PLA2R antibody levels
timeFrame: 3 months compared to baseline
Secondary outcomes:
measure: efficacy: immunological complete response (ICR) rate
timeFrame: ICR rate at 3 months, 6 months, 12 months and 24 months
measure: efficacy: overall proteinuria response (OPR) rate
timeFrame: OPR rate at 6 months, 12 months and 24 months.
measure: safety: determined by the frequency, incidence and severity of TEAEs
timeFrame: through treatment completion, an average of 3 months per treatment period
measure: PK profile
timeFrame: through study completion, an average of 1 year
measure: immunogenicity
timeFrame: through study completion, an average of 1 year
Other outcomes:
Locations:
city: Tbilisi
country: Georgia
facility: Managadze National Center of Urology
city: Tbilisi
country: Georgia
facility: Tbilisi State Medical University and Ingorokva High Medical Technology University Clinic
city: Aachen
country: Germany
facility: University Hospital Aachen
city: Berlin
country: Germany
facility: Charite
city: Düsseldorf
country: Germany
facility: DaVita Clinical Research
city: Essen
country: Germany
facility: Uniklinikum
city: Mainz
country: Germany
facility: Hospital of Johannes Gutenberg University
city: Athens
country: Greece
facility: General Hospital of Athens
city: Heraklion
country: Greece
facility: General Hospital of Heraklion Venizeleio-Papaneio
city: Patras
country: Greece
facility: University General Hospital of Patras
city: Thessaloníki
country: Greece
facility: General Hospital of Thessaloniki
city: Chuncheon
country: Korea, Republic of
facility: Hallym University Sacred Heart Hospital
city: Jeju
country: Korea, Republic of
facility: JeJu National University Hospital
city: Seoul
country: Korea, Republic of
facility: Konkuk University Hospital
city: Seoul
country: Korea, Republic of
facility: Kyung Hee University Hospital at Gangdong
city: Seoul
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Moscow
country: Russian Federation
facility: Botkin Hospital Moscow
city: Saint Petersburg
country: Russian Federation
facility: First Pavlov State Medical University of St. Petersburg
city: Kaohsiung
country: Taiwan
facility: Chang Gung Memorial Hospital
city: New Taipei City
country: Taiwan
facility: Shuang Ho Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: London
country: United Kingdom
facility: Kings College
city: Nottingham
country: United Kingdom
facility: Nottingham Renal and Transplant Unit
Study officials:
affiliation: HI-Bio, A Biogen Company
name: Medical Director
role: STUDY_DIRECTOR
References: