Clinical trial NCT04652570: Efficacy and Safety of VB119 in Subjects With Membranous Nephropathy
Official title: A Phase 1b/2a Study of VB119 in Adult Subjects With Primary Membranous Nephropathy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Membranous Nephropathy
Lead sponsor: Tenet Medicines
Sponsor class: INDUSTRY
First posted: 2020-12-03
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This study is a Phase 1b/2a, open-label, sequential-cohort, dose escalation, and dose expansion study to evaluate the safety, tolerability, PK, and PD of VB119 in subjects with primary MN


Eligibility criteria: Inclusion Criteria:

1. Is ≥ 18 years of age at the time of informed consent;
2. Has a kidney biopsy-proven diagnosis of primary MN within the past 10 years; Note: It is preferable that subjects enrolled have kidney biopsy tissue samples that are positive for anti-PLA2R antibody staining. Subjects with kidney biopsy-proven diagnosis of primary MN \>10 years and ≤20 years that meet all other eligibility criteria may be enrolled after discussion with the Medical Monitor.
3. 3. Has a documented laboratory history of nephrotic range proteinuria (defined as either greater than or equal to 3.5 g total protein per 24-hour urine collection or greater than or equal to 3.5 g/g UPCR by spot collection) AND has proteinuria with a UPCR greater than or equal to 2.0 g/g based on 2 consecutive spot urine (first morning void) sample collections obtained within 14 days of each other during the Screening Period. Both samples must qualify;
4. Has systolic blood pressure (BP) \<160 mmHg or diastolic BP \<100 mmHg after 5 minutes of rest at Screening;
5. Is willing and able to provide written informed consent prior to Screening;
6. Female subjects of non-childbearing potential must be either surgically sterile (hysterectomy, bilateral tubal ligation, salpingectomy, and/or bilateral oophorectomy at least 26 weeks before the Screening Visit) or postmenopausal, defined as spontaneous amenorrhea for at least 2 years, with follicle-stimulating hormone in the postmenopausal range at Screening, based on the central laboratory's ranges;
7. Female subjects of childbearing potential (ie, ovulating, premenopausal, or not surgically sterile) and all male subjects must use a medically accepted, highly effective contraceptive regimen during their participation in the study and for 125 days after the last administration of study drug.
8. Male subjects must agree to abstain from sperm donation through 125 days after administration of the last dose of study drug.

Exclusion Criteria:

1. Has an eGFR \<45 mL/min/1.73 m2 at Screening utilizing the Chronic Kidney Disease Epidemiology Collaboration formula confirmed by the central laboratory;
2. Has an absolute neutrophil count \<1.5 x 10/L;
3. Has a white blood cell count \<3.0 x 10/L;
4. Has secondary causes of MN (eg, malignancy, hepatitis B or C, human immunodeficiency virus \[HIV\], systemic lupus erythematosus \[SLE\], or other autoimmune diseases \[eg, thyroiditis\], drug-induced);
5. Has a diagnosis or history of SLE (including non renal disease);
6. Has type 1 or 2 diabetes mellitus;
7. Has an acute, chronic, or latent infection, including tuberculosis, hepatitis, HIV, or chronic urinary tract infections;

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: Through study completion, an average of 18 months
measure: Incidence of Clinical Laboratory Assessments
timeFrame: Through study completion, an average of 18 months
Secondary outcomes:
measure: % of Patients with Anti-Drug Antibodies
timeFrame: Through study completion, an average of 18 months
measure: Maximum Plasma Concentration [Cmax]
timeFrame: Week 12
measure: Time to Maximum Plasma Concentration [Tmax]
timeFrame: Week 12
measure: % of patients achieving complete remission of proteinuria
timeFrame: Through study completion, an average of 18 months
measure: Anti-PLA2R Antibody Assessment
timeFrame: Through study completion, an average of 18 months
measure: Quality of Life as assessed by PROMIS
timeFrame: Through study completion, an average of 18 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Clinical Reserach Site
state: California
city: Albany
country: United States
facility: Clinical Research Site
state: New York
city: Bethlehem
country: United States
facility: Clinical Research Site
state: Pennsylvania
city: Dallas
country: United States
facility: Clinical Research Site
state: Texas
Study officials:
affiliation: ValenzaBio, Inc.
name: Keenan
role: STUDY_CHAIR
References: