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Evaluation of Glucocorticoids Plus Rituximab Compared to Glucocorticoids Plus Placebo for the Treatment of Patients With Newly-Diagnosed or Relapsing IgA Vasculitis (RIGA)

Primary Purpose

IgA Vasculitis

Status
Recruiting
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Rituximab Injection
placebo
Sponsored by
Hopital Foch
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for IgA Vasculitis focused on measuring Rituximab

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Biopsy-proven diagnosis of IgAV according to Chapel Hill Consensus Conference definitions
  • Patient aged of 18 years or older
  • Patients with newly-diagnosed disease or relapsing disease at the time of screening, with an active disease defined by active manifestations attributable to IgAV
  • Patients with severe involvement of at least one organ
  • Patients within the first 21 days following initiation/increase of glucocorticoids at a dose < 1 mg/kg/day
  • Has signed an informed consent form prior to any study related procedures
  • Affiliated to a national health insurance

Exclusion Criteria:

  • Patients with ANCA-associated vasculitis, or other vasculitis, defined by the ACR criteria and/or the Chapel Hill Consensus Conference,
  • Patients with IgAV in remission of the disease,
  • Patients with severe cardiac failure defined as class IV in New York Heart Association,
  • Patients with severe, uncontrolled cardiac disease,
  • Patients with acute infections or chronic active infections (including HIV, HBV or HCV),
  • Patients with active cancer or recent malignancy (<5 years), except basocellular carcinoma and prostatic cancer of low activity controlled by hormonal treatment,
  • Pregnant women and breastfeeding. Patients with childbearing potential must use reliable contraceptive methods throughout the study and at least for 12 months after the last study drug administration,
  • Patients with IgAV who have already been treated with rituximab within the previous 12 months,
  • Patients treated with immunosuppressive therapy within the last 3 months,
  • Patients with hypersensitivity to human or chimeric monoclonal antibodies,
  • Patients with contraindication to use rituximab,
  • Patients treated with any concomitant drugs contraindicated for use with the rituximab according to its SmPC,
  • Patients with contraindication to use routine care treatments (Glucocorticoids, Angiotensin-converting-enzyme (ACEis) or angiotensin receptor blockers (ARBs), dexchlorphéniramine),
  • Patients in a severely immunocompromised state,
  • Patients with other uncontrolled diseases, including drug or alcohol abuse, severe psychiatric disorders, that could interfere with his/her compliance to protocol requirements,
  • Patients currently participating in another clinical study or 3 months prior to randomization,
  • Patients suspected not to be observant to the proposed treatments,
  • Patients unable to give written informed consent prior to participation in the study
  • Being deprived of liberty or under guardianship.

Sites / Locations

  • Hopital La Cavale Blanche
  • CHU Clermont Ferrand
  • CHU Clermont Ferrand
  • Hôpital Edouard Herriot
  • CHU MarseilleRecruiting
  • APHM de La Timone
  • Hôpital André Grégoire
  • CHU Nantes
  • CHU Nîmes (Caremeau)Recruiting
  • Hôpital Cochin
  • CHU Strasbourg
  • Hôpital Foch
  • CHU Toulouse
  • CHRU Bretonneau

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

experimental group

control group

Arm Description

Experimental therapeutic strategy based on the use of rituximab in combination with glucocorticoids

Control therapeutic strategy based on glucocorticoids plus placebo

Outcomes

Primary Outcome Measures

Rituximab efficacy
The proportion of patients alive who achieved remission with a prednisone dose of 0 mg/day at both days 180 and 360

Secondary Outcome Measures

Rituximab efficacy delay
Proportion of patients in remission at different research times
Rituximab efficacy delay
Proportion of patients with BVAS=0 (or BVAS of ≤5 if all scores were due to persistent hematuria or proteinuria) and a prednisone dose ≤5 mg/day at days 180 and 360
IgAV relapses
Number of major and minor relapse at 12 months
IgAV relapses
Cumulative incidence of relapse at 12 months
IgAV relapses
Time to first IgAV relapse
Number of participants with adverse events for the safety analyse
Adverse events, expressed as adverse events according to the CTCAE toxicity grading system per patient-year at days 180 and 360 for the following adverse events combined: death (all causes), grade 2 or higher leukopenia or thrombocytopenia, grade 3 or higher infections, malignancies, venous thromboembolic events, hospitalization resulting either from the disease or from a complication due to the study treatment, infusion reactions (within 24 hours of infusion) that result in the cessation of further infusions, death
The glucocorticoids dose
Prednisone dosage at days 180 and 360 in the two treatment groups
The glucocorticoids dose
Area under the curve for prednisone dose at days 180 and 360 in the two treatment groups
Number of patients with a complete or partial renal remission & renal outcome remission
Proportion of patients in complete renal and partial renal remission at days 180 and 360; - Renal parameters at days 180 and 360 compared with baseline
Number of patients with a complete or partial renal remission & renal outcome remission
Renal parameters at days 180 and 360 compared with baseline
The sequelae assessed by the Vasculitis Damage Index
The Vasculitis Damage Index at days 180 and 360 in the two treatment groups
Patient survival and quality of life
Quality of life as measured by the HAQ and SF-36 questionnaires at days 180 and 360
Patient survival and quality of life
The patient-reported outcomes (PRO) including patient-reported disease activity, anxiety and depression, burden of the disease and treatment and adherence to treatment, at days 180 and 360 after randomization in the two treatment groups, and during the long-term follow-up
Patient survival and quality of life
Number of patient survival
To assess renal outcome
A complete response is defined as a decrease in the proteinuria level to < 0.5 gm/ day (or urine protein-to-creatinine ratio <0.5 gm/gm), the disappearance of hematuria, and no decrease in the eGFR of more than 20% from baseline.

Full Information

First Posted
August 9, 2021
Last Updated
June 13, 2023
Sponsor
Hopital Foch
Collaborators
Ministry of Health, France
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1. Study Identification

Unique Protocol Identification Number
NCT05329090
Brief Title
Evaluation of Glucocorticoids Plus Rituximab Compared to Glucocorticoids Plus Placebo for the Treatment of Patients With Newly-Diagnosed or Relapsing IgA Vasculitis
Acronym
RIGA
Official Title
Evaluation of Glucocorticoids Plus Rituximab Compared to Glucocorticoids Plus Placebo for the Treatment of Patients With Newly-Diagnosed or Relapsing IgA Vasculitis: A Prospective, Randomized, Controlled, Double-blind Study
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 11, 2022 (Actual)
Primary Completion Date
March 11, 2025 (Anticipated)
Study Completion Date
March 11, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hopital Foch
Collaborators
Ministry of Health, France

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Systemic vasculitis are inflammatory diseases of the blood vessels, responsible for systemic manifestations. Among the systemic vasculitis affecting small blood vessels, IgA vasculitis (IgAV) is one of the most common forms and mainly affects the skin, joints, kidneys and gastrointestinal tract. Kidney and gastrointestinal damage can be serious, causing complications and life-threatening sequelae, especially in adults. The treatment of adult-onset IgAV is still a matter of debate. Glucocorticoids have been the standard of care for inducing remission for years in severe forms of IgAV. However, not all patients achieve remission and may experience disease flares associated with increased morbidity and mortality. In addition, the cumulative side effects of glucocorticoids are also major causes of long-term adverse events and death.Rituximab (RTX), an anti-CD20 monoclonal antibody, has been shown to be spectacularly effective in inducing remission in d 'other small vascular vessels, in particular ANCA-associated vasculitis and cryoglobulinemic vasculitis, with an acceptable safety profile. Recently, a multicenter observational study suggested that RTX was an effective and safe therapeutic option for treating relapsed and / or refractory adult IgAV. Overall, RTX may be an effective and safe therapeutic approach in adult IgAVs, justifying the need for a prospective randomized controlled trial evaluating Rituximab as an induction of remission for adult IgAV.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
IgA Vasculitis
Keywords
Rituximab

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Design of trial : Controlled (the comparator is a Placebo) Randomised Double blind Parallel groupe With a double layering
Masking
ParticipantInvestigator
Masking Description
This trial will be comparative, randomized, double-blind and double-dummy in order to limit performance and evaluation bias. Neither patients, nor physicians will know the treatments allocated to their patients. Investigators will be in blind of the leukocyte formula during all study period, from day 1. Neither patients, nor physicians will know the treatments allocated to their patients. Investigators will be in blind of the CD19+ count during all study period, from day 15.
Allocation
Randomized
Enrollment
72 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
experimental group
Arm Type
Experimental
Arm Description
Experimental therapeutic strategy based on the use of rituximab in combination with glucocorticoids
Arm Title
control group
Arm Type
Placebo Comparator
Arm Description
Control therapeutic strategy based on glucocorticoids plus placebo
Intervention Type
Drug
Intervention Name(s)
Rituximab Injection
Other Intervention Name(s)
Rixathon, Truxima
Intervention Description
anti-CD20 monoclonal antibody leading to B-cell depletion, in relapsing and/or refractory IgAV patients
Intervention Type
Drug
Intervention Name(s)
placebo
Other Intervention Name(s)
NaCl
Intervention Description
placebo experimental treatment
Primary Outcome Measure Information:
Title
Rituximab efficacy
Description
The proportion of patients alive who achieved remission with a prednisone dose of 0 mg/day at both days 180 and 360
Time Frame
360 days
Secondary Outcome Measure Information:
Title
Rituximab efficacy delay
Description
Proportion of patients in remission at different research times
Time Frame
360 days
Title
Rituximab efficacy delay
Description
Proportion of patients with BVAS=0 (or BVAS of ≤5 if all scores were due to persistent hematuria or proteinuria) and a prednisone dose ≤5 mg/day at days 180 and 360
Time Frame
360 days
Title
IgAV relapses
Description
Number of major and minor relapse at 12 months
Time Frame
180 days
Title
IgAV relapses
Description
Cumulative incidence of relapse at 12 months
Time Frame
180 days
Title
IgAV relapses
Description
Time to first IgAV relapse
Time Frame
180 days
Title
Number of participants with adverse events for the safety analyse
Description
Adverse events, expressed as adverse events according to the CTCAE toxicity grading system per patient-year at days 180 and 360 for the following adverse events combined: death (all causes), grade 2 or higher leukopenia or thrombocytopenia, grade 3 or higher infections, malignancies, venous thromboembolic events, hospitalization resulting either from the disease or from a complication due to the study treatment, infusion reactions (within 24 hours of infusion) that result in the cessation of further infusions, death
Time Frame
360 days
Title
The glucocorticoids dose
Description
Prednisone dosage at days 180 and 360 in the two treatment groups
Time Frame
360 days
Title
The glucocorticoids dose
Description
Area under the curve for prednisone dose at days 180 and 360 in the two treatment groups
Time Frame
360 days
Title
Number of patients with a complete or partial renal remission & renal outcome remission
Description
Proportion of patients in complete renal and partial renal remission at days 180 and 360; - Renal parameters at days 180 and 360 compared with baseline
Time Frame
360 days
Title
Number of patients with a complete or partial renal remission & renal outcome remission
Description
Renal parameters at days 180 and 360 compared with baseline
Time Frame
360 days
Title
The sequelae assessed by the Vasculitis Damage Index
Description
The Vasculitis Damage Index at days 180 and 360 in the two treatment groups
Time Frame
360 days
Title
Patient survival and quality of life
Description
Quality of life as measured by the HAQ and SF-36 questionnaires at days 180 and 360
Time Frame
360 days
Title
Patient survival and quality of life
Description
The patient-reported outcomes (PRO) including patient-reported disease activity, anxiety and depression, burden of the disease and treatment and adherence to treatment, at days 180 and 360 after randomization in the two treatment groups, and during the long-term follow-up
Time Frame
360 days
Title
Patient survival and quality of life
Description
Number of patient survival
Time Frame
360 days
Title
To assess renal outcome
Description
A complete response is defined as a decrease in the proteinuria level to < 0.5 gm/ day (or urine protein-to-creatinine ratio <0.5 gm/gm), the disappearance of hematuria, and no decrease in the eGFR of more than 20% from baseline.
Time Frame
360 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Biopsy-proven diagnosis of IgAV according to Chapel Hill Consensus Conference definitions Patient aged of 18 years or older Patients with newly-diagnosed disease or relapsing disease at the time of screening, with an active disease defined by active manifestations attributable to IgAV Patients with severe involvement of at least one organ Patients within the first 21 days following initiation/increase of glucocorticoids at a dose < 1 mg/kg/day Has signed an informed consent form prior to any study related procedures Affiliated to a national health insurance Exclusion Criteria: Patients with ANCA-associated vasculitis, or other vasculitis, defined by the ACR criteria and/or the Chapel Hill Consensus Conference, Patients with IgAV in remission of the disease, Patients with severe cardiac failure defined as class IV in New York Heart Association, Patients with severe, uncontrolled cardiac disease, Patients with acute infections or chronic active infections (including HIV, HBV or HCV), Patients with active cancer or recent malignancy (<5 years), except basocellular carcinoma and prostatic cancer of low activity controlled by hormonal treatment, Pregnant women and breastfeeding. Patients with childbearing potential must use reliable contraceptive methods throughout the study and at least for 12 months after the last study drug administration, Patients with IgAV who have already been treated with rituximab within the previous 12 months, Patients treated with immunosuppressive therapy within the last 3 months, Patients with hypersensitivity to human or chimeric monoclonal antibodies, Patients with contraindication to use rituximab, Patients treated with any concomitant drugs contraindicated for use with the rituximab according to its SmPC, Patients with contraindication to use routine care treatments (Glucocorticoids, Angiotensin-converting-enzyme (ACEis) or angiotensin receptor blockers (ARBs), dexchlorphéniramine), Patients in a severely immunocompromised state, Patients with other uncontrolled diseases, including drug or alcohol abuse, severe psychiatric disorders, that could interfere with his/her compliance to protocol requirements, Patients currently participating in another clinical study or 3 months prior to randomization, Patients suspected not to be observant to the proposed treatments, Patients unable to give written informed consent prior to participation in the study Being deprived of liberty or under guardianship.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Romain Paule, Dr
Phone
33 1 46 25 25 76
Email
r.paule@hopital-foch.com
First Name & Middle Initial & Last Name or Official Title & Degree
Elisabeth Hullier-Ammar, Dr
Email
drci-promotion@hopital-foch.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Romain Paule, Dr
Organizational Affiliation
Hôpital Foch
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hopital La Cavale Blanche
City
Brest
ZIP/Postal Code
29200
Country
France
Individual Site Status
Active, not recruiting
Facility Name
CHU Clermont Ferrand
City
Clermont-Ferrand
ZIP/Postal Code
63000
Country
France
Individual Site Status
Active, not recruiting
Facility Name
CHU Clermont Ferrand
City
Clermont-Ferrand
ZIP/Postal Code
63003
Country
France
Individual Site Status
Active, not recruiting
Facility Name
Hôpital Edouard Herriot
City
Lyon
ZIP/Postal Code
69003
Country
France
Individual Site Status
Active, not recruiting
Facility Name
CHU Marseille
City
Marseille
ZIP/Postal Code
13005
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Noémie Jourde-Chiche, Dr
Email
noemie.jourde@ap-hm.fr
Facility Name
APHM de La Timone
City
Marseille
ZIP/Postal Code
13385
Country
France
Individual Site Status
Active, not recruiting
Facility Name
Hôpital André Grégoire
City
Montreuil
ZIP/Postal Code
93100
Country
France
Individual Site Status
Active, not recruiting
Facility Name
CHU Nantes
City
Nantes
ZIP/Postal Code
44093
Country
France
Individual Site Status
Active, not recruiting
Facility Name
CHU Nîmes (Caremeau)
City
Nîmes
ZIP/Postal Code
30029
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Olivier Moranne, Dr
Email
olivier.moranne@chu-nimes.fr
Facility Name
Hôpital Cochin
City
Paris
ZIP/Postal Code
75679
Country
France
Individual Site Status
Active, not recruiting
Facility Name
CHU Strasbourg
City
Strasbourg
ZIP/Postal Code
67091
Country
France
Individual Site Status
Active, not recruiting
Facility Name
Hôpital Foch
City
Suresnes
ZIP/Postal Code
92150
Country
France
Individual Site Status
Active, not recruiting
Facility Name
CHU Toulouse
City
Toulouse
ZIP/Postal Code
31059
Country
France
Individual Site Status
Active, not recruiting
Facility Name
CHRU Bretonneau
City
Tours
ZIP/Postal Code
37044
Country
France
Individual Site Status
Active, not recruiting

12. IPD Sharing Statement

Learn more about this trial

Evaluation of Glucocorticoids Plus Rituximab Compared to Glucocorticoids Plus Placebo for the Treatment of Patients With Newly-Diagnosed or Relapsing IgA Vasculitis

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