This is a Randomized, Double-Blind, Placebo-Controlled Study designed to assess safety, tolerability, and efficacy of NM8074 in AAV patients when used in combination with Standard of Care (SOC) cyclophosphamide/azathioprine or rituximab plus corticosteroids.
The proposed study, NM8074-AAV-501, will initially assign six (6) patients per cohort in a 2-cohort trial. In the first cohort, we will evaluate a biweekly dosing regimen with NM8074 and SOC whereas in the second cohort, we will evaluate placebo with SOC. These studies will assess safety, tolerability, and efficacy of NM8074 in AAV patients when used in combination with SOC cyclophosphamide/azathioprine or rituximab plus corticosteroids.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
12
NM8074 will be administered as an intravenous infusion. In Cohort 1, all subjects will be administered 20 mg/kg of NM8074 intravenously every two weeks for a total of 7 doses from Day 1 to Day 85 of the Treatment Period.
Saline Placebo will be administered as an intravenous infusion. In Cohort 2, all subjects will be administered saline placebo intravenously every two weeks for a total of 7 doses from Day 1 to Day 85 of the Treatment Period.
Proportion of subjects achieving disease response at Day 85 defined as BVAS percent decrease of at least 50% from baseline.
Time frame: Up to Study Day 85
Number of patients with ANCA positivity (anti-PR3 and anti-MPO)
Time frame: Up to Study Day 133
Change from Baseline or Percent Change from Baseline in BVAS (Birmingham Vasculitis Activity Score)
Time frame: Up to Study Day 133
Change from Baseline or Percent Change from Baseline in Vasculitis Damage Index (VDI)
Time frame: Up to Study Day 133
Change from Baseline or Percent Change from Baseline in C-reactive protein concentration
Time frame: Up to Study Day 133
Proportion of patients requiring rescue glucocorticoid treatment
Time frame: Up to Study Day 133
Proportion of patients achieving disease remission on Day 85 defined as BVAS of 0.
Time frame: Up to Study Day 85
Percent Change from Baseline in urinary Monocyte Chemoattractant Protein-1 (MCP-1):creatinine ratio
Time frame: Up to Study Day 133
proportion of subject achieving renal response at Day 85
An \>20% increase from baseline to Day 85 in eGFR, A \>30% decrease from baseline to Day 85 in hematuria, A \>30% decrease from baseline to Day 85 in albuminuria
Time frame: Up to Study Day 85
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Change from Baseline or Percent Change from Baseline in quality of life (QoL) Assessed via the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale, Version 4.
The FACIT-fatigue scale is a 13-item patient-reported measure of fatigue with a 7-day recall period. Items are scored on a 0 - 4 response scale ranging from "Not at all" to "Very much so". All items are summed to create a single fatigue score with a range from 0 to 52 with a better quality of life indicated by a higher score.
Time frame: Up to Study Day 133
Change from Baseline or Percent Change from Baseline in Quality of Life (QoL) Assessed via the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 Scale (QLQ- C30), Version 3.0
All EORTC QLQ-C30 scales and single-item measures range from 0 to 100. This includes 3 symptom scales (fatigue, pain, nausea and vomiting), 5 functional scales (physical, role, cognitive, emotional, and social), single-item questions addressing symptoms like insomnia, dyspnea, loss of appetite, and others that are commonly reported by cancer patients, and the perceived financial impact of the disease. A higher score is associated with a greater quality of life for global health status.
Time frame: Up to Study Day 133
Change from Baseline or Percent Change from Baseline in Quality of Life (QoL) assessed via EQ-5D-5L
The EuroQol 5 Dimension 5 Level (EQ-5D-5L) is a self-assessed, health related QoL which measures QoL in a 5-component scale including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The digits for 5 dimensions can be combined in a 5-digit number describing the respondent's health state.
Time frame: Up to Study Day 133
Change from Baseline or Percent Change from Baseline in Quality of Life (QoL) assessed via SF-36v2
The Short Form Health Survey version-2.0 (SF-36v2) questionnaire is a short-form health survey that measures each of the following eight health domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. Scales are standardized with a scoring algorithm from 0 to 100.
Time frame: Up to Study Day 133