Pharmacokinetic Study of Rituximab Induction Regimen in ANCA-associated Vasculitis (MONITUX)

Pharmacokinetic Study of Rituximab Induction Regimen in ANCA-associated Vasculitis : a Predictive Factor of Clinical Outcome? (MONITUX)

The aim of the investigators' study is to evaluate whether monitoring serum rituximab levels could be an interesting tool in the follow-up of ANCA-associated vasculitis patients.

All consecutive patients, hospitalized for a new diagnosis of ANCA-associated vasculitis or the relapse of a known ANCA-associated vasculitis, in which the decision to start an induction regimen with rituximab has been taken, will be included.

Serum rituximab levels (along with serum anti-rituximab antibodies levels) will be determined (at M+1 and M+3) and the correlation with clinical outcome at M+6 will be analyzed.

Study Overview

• Status: Terminated
• Conditions: Microscopic Polyangiitis; Granulomatosis, Wegener's
• Intervention / Treatment: Other: blood specimen

• Study Type: Observational
• Enrollment (Actual): 28

Contacts and Locations

Study Locations

• France
  • Lyon, France, 69003
    • Hôpital Edouard Herriot
  • Lyon, France, 69317
    • Hopital de la croix rousse
  • Pierre-Bénite, France, 69495
    • CH Lyon Sud
  • Saint-Etienne, France, 42055
    • CHU Saint-Etienne

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Granulomatosis with polyangiitis or microscopic polyangiitis (according to Chapel Hill criterions), with or without detectable ANCA

Description

Inclusion Criteria:

• Age > 18 years
• Granulomatosis with polyangiitis or microscopic polyangiitis (according to Chapel Hill criterions), with or without detectable ANCA
• Decision taken to start an induction regimen with rituximab
• Informed and having signed the study consent form
• If of child-bearing potential, female patients will have use an effective method of contraception during RTX (rituximab) treatment and in the 12 months following RTX treatment stop
• no-breast-feeding during RTX treatment and in the 12 months following RTX treatment stop

Exclusion Criteria:

• Other primary or secondary systemic vasculitis
• Incapacity or refusal to sign the informed consent form
• Incapacity or refusal to adhere to treatment or perform the follow-up examinations required by the study
• Allergy, documented hypersensitivity or contraindication to the medications used in the present study (corticosteroids, rituximab)
• severe active infection
• Patient with severe heart failure (stage NYHA IV) or any other unstable heart disease Pregnancy, except for cases where the expected benefit oj treatment seems to surpass the potential risks
• Patients with active hepatitis B
• Any live vaccine within four weeks prior to the first infusion of RTX

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Rituximab; a classical induction regimen with rituximab (decision taken before inclusion), implying an infusion of 375mg/m² per week, for 4 consecutive weeks (from week -3 until week 0) with blood specimen.	Other: blood specimen; blood specimen for serum rituximab level and serum anti-rituximab level at M1 and M3 after stop of induction rituximab treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
serum rituximab levels	rituximab level comparison between number of non-responders and number of responders after rituximab induction regimen. The number of non-responders is defined by a Birmingham Vascularitis Activity score > 0, 6 months after stop of induction regimen	1 month after stop of rituximab induction regimen

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
serum rituximab levels	rituximab level comparison between number of non-responders and number of responders after rituximab induction regimen. The number of non-responders is defined by a Birmingham Vascularitis Activity score > 0 six months after stop of induction regimen	3 months after stop of rituximab induction regimen
serum rituximab levels	rituximab level comparison between number of non-responders and number of responders after rituximab induction regimen. The number of non-responders is defined by a Birmingham Vascularitis Activity score > 0 six months after stop of induction regimen	6 months after stop of rituximab induction regimen
serum anti-rituximab antibodies	serum anti-rituximab antibodies level comparison between number of non-responders and number of responders after rituximab induction regimen. The number of non-responders is defined by a Birmingham Vascularitis Activity score > 0 six months after stop of induction regimen	1 month after stop of rituximab induction regimen
serum anti-rituximab antibodies	serum anti-rituximab antibodies level comparison between number of non-responders and number of responders after rituximab induction regimen. The number of non-responders is defined by a Birmingham Vascularitis Activity score > 0 six months after stop of induction regimen	3 months after stop of rituximab induction regimen
serum anti-rituximab antibodies	serum anti-rituximab antibodies level comparison between number of non-responders and number of responders after rituximab induction regimen. The number of non-responders is defined by a Birmingham Vascularitis Activity score > 0 six months after stop of induction regimen	6 months after stop of rituximab induction regimen
Serum B lymphocytes (CD19+ cells) levels	Serum B lymphocytes (CD19+ cells) levels comparison between number of non-responders and number of responders after rituximab induction regimen. The number of non-responders is defined by a Birmingham Vascularitis Activity score > 0 six months after stop of induction regimen	1 month after stop of rituximab induction regimen
Serum B lymphocytes (CD19+ cells) levels	Serum B lymphocytes (CD19+ cells) levels comparison between number of non-responders and number of responders after rituximab induction regimen. The number of non-responders is defined by a Birmingham Vascularitis Activity score > 0 six months after stop of induction regimen	3 months after stop of rituximab induction regimen
Serum B lymphocytes (CD19+ cells) levels	Serum B lymphocytes (CD19+ cells) levels comparison between number of non-responders and number of responders after rituximab induction regimen. The number of non-responders is defined by a Birmingham Vascularitis Activity score > 0 six months after stop of induction regimen	6 months after stop of rituximab induction regimen
patient number with adverse event	frequency and nature of rituximab-attributed adverse events	from start of induction rituximab regimen until six monthes after stop of induction regimen

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Collaborators: Theradiag
• Investigators: Principal Investigator: Pascal CATHEBRAS, PHD, CHU Saint-Etienne

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2015
• Primary Completion (Actual): June 12, 2020
• Study Completion (Actual): June 12, 2020

Study Registration Dates

• First Submitted: June 10, 2015
• First Submitted That Met QC Criteria: June 17, 2015
• First Posted (Estimate): June 18, 2015

Study Record Updates

• Last Update Posted (Actual): November 16, 2020
• Last Update Submitted That Met QC Criteria: November 12, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Respiratory Tract Diseases; Immune System Diseases; Autoimmune Diseases; Lung Diseases; Lung Diseases, Interstitial; Cerebral Small Vessel Diseases; Systemic Vasculitis; Vasculitis; Granulomatosis with Polyangiitis; Microscopic Polyangiitis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
• Other Study ID Numbers: 1508058; 2015-001807-29 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No