Clinical trial NCT05329090: Evaluation of Glucocorticoids Plus Rituximab in Patients with Newly-Diagnosed or Relapsing IgA Vasculitis
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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: IgA Vasculitis
Keywords: Rituximab
Lead sponsor: Hopital Foch
Sponsor class: OTHER
Collaborators: name: Ministry of Health, France
First posted: 2022-04-14
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Design of trial :

* Controlled (the comparator is a Placebo)
* Randomised
* Double blind
* Parallel groupe
* With a double layering
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Rituximab efficacy
timeFrame: 180 days
measure: Rituximab efficacy
timeFrame: 360 days
Secondary outcomes:
measure: Efficacy of rituximab-based regimen to induce remission
timeFrame: 180 days
measure: Efficacy of rituximab-based regimen to induce remission
timeFrame: 360 days
measure: Assessement the duration of remission
timeFrame: 360 days
measure: Assessment of patients achieving a complete or partial renal remission & renal outcome remission
timeFrame: 180 days
measure: Assessment of patients achieving a complete or partial renal remission & renal outcome remission
timeFrame: 360 days
measure: Measure of glucocorticoids dose
timeFrame: 160 days
measure: Measure of glucocorticoids dose
timeFrame: 360 days
measure: Number of participants with adverse events for the safety analyse
timeFrame: 360 days
measure: The sequelae assessed by the Vasculitis Damage Index
timeFrame: 180 days
measure: The sequelae assessed by the Vasculitis Damage Index
timeFrame: 360 days
measure: Quality of life of patients
timeFrame: 180 days
measure: Quality of life of patients
timeFrame: 360 days
measure: Patient reported outcome
timeFrame: 360 days
measure: Patient survival
timeFrame: 360 days
Other outcomes:
Locations:
city: Brest
country: France
facility: Hopital La Cavale Blanche
city: Clermont-Ferrand
country: France
facility: CHU Clermont Ferrand
city: Clermont-Ferrand
country: France
facility: CHU Clermont Ferrand
city: Lyon
country: France
facility: Hôpital Edouard Herriot
city: Marseille
country: France
facility: CHU Marseille
city: Marseille
country: France
facility: APHM de La Timone
city: Montreuil
country: France
facility: Hôpital André Grégoire
city: Nantes
country: France
facility: CHU Nantes
city: Nîmes
country: France
facility: CHU Nîmes (Caremeau)
city: Paris
country: France
facility: Hôpital Cochin
city: Strasbourg
country: France
facility: CHU Strasbourg
city: Suresnes
country: France
facility: Hôpital Foch
city: Toulouse
country: France
facility: CHU Toulouse
city: Tours
country: France
facility: CHRU Bretonneau
Study officials:
affiliation: Hôpital Foch
name: Romain Paule, Dr
role: PRINCIPAL_INVESTIGATOR
References: