Informations générales (source: ClinicalTrials.gov)
Salvage Therapy for Patients with Inadequate Response to Standard of Care Therapy in Granulomatosis with Polyangiitis
Interventional
Phase 3
Assistance Publique - Hôpitaux de Paris (Voir sur ClinicalTrials)
mars 2025
janvier 2029
12 septembre 2025
The purpose of this study is to identify the most promising therapeutic strategy for
patients with granulomatosis with polyangiitis and inadequate response to standard of
care therapy. It will evaluate the efficacy to induce remission of three different
salvage strategies including: a combination of rituximab with addition of a conventional
disease-modifying antirheumatic drugs (either methotrexate, azathioprine or mycophenolate
mofetil, but preferentially methotrexate); tocilizumab; or tofacitinib.
Etablissements
Critères
Tous
Inclusion Criteria:
- Newly diagnosed or relapsing granulomatosis with polyangiitis according to American
College of Rheumatology criteria, EMA classification algorithm and/or the 2012
revised Chapel Hill Consensus Conference definition.
- Aged 18 years or older
- Active clinical manifestations attributable to GPA
- An inadequate response to previous standard of care therapy including either :
1. A combination of glucocorticoids plus cyclophosphamide
2. AND /OR a combination of glucocorticoids plus rituximab
- An inadequate response to treatment defined as follows:
1. A progressive disease unresponsive to previous standard of care therapy after
12 weeks of treatment
2. Or a lack of response, defined as < 50% reduction in the disease activity
score, after 12 weeks of treatment
3. Or a persistent active disease attributable to either a vasculitic or a
granulomatous manifestation of GPA that requires the maintenance of
corticosteroids ≥ 7.5 mg/day of equivalent prednisone after ≥ 12 weeks of
treatment.
- A stable dose of oral glucocorticoids of ≥ 7.5 mg/day of equivalent prednisone
within the 4 weeks before enrollment. Pulses of methylprednisolone (1 to 3 pulses of
7.5 to 15 mg/kg each; ≤ 1000 mg) are allowed if necessary, according to severity
before starting the experimental treatment.
- A stable dose of conventional disease-modifying anti-rheumatic drugs (cDMARD) within
4 weeks before enrollment if the patient is currently treated with a cDMARD
- Patients must have the ability to understand the requirements of the study, provide
written informed consent prior to participation in the study (including consent for
the use and disclosure of research-related health information) and comply with the
study protocol procedures (including required study visits)
- Patients must have an affiliation with a mode of social security (profit or being
entitled)
- Newly diagnosed or relapsing granulomatosis with polyangiitis according to American
College of Rheumatology criteria, EMA classification algorithm and/or the 2012
revised Chapel Hill Consensus Conference definition.
- Aged 18 years or older
- Active clinical manifestations attributable to GPA
- An inadequate response to previous standard of care therapy including either :
1. A combination of glucocorticoids plus cyclophosphamide
2. AND /OR a combination of glucocorticoids plus rituximab
- An inadequate response to treatment defined as follows:
1. A progressive disease unresponsive to previous standard of care therapy after
12 weeks of treatment
2. Or a lack of response, defined as < 50% reduction in the disease activity
score, after 12 weeks of treatment
3. Or a persistent active disease attributable to either a vasculitic or a
granulomatous manifestation of GPA that requires the maintenance of
corticosteroids ≥ 7.5 mg/day of equivalent prednisone after ≥ 12 weeks of
treatment.
- A stable dose of oral glucocorticoids of ≥ 7.5 mg/day of equivalent prednisone
within the 4 weeks before enrollment. Pulses of methylprednisolone (1 to 3 pulses of
7.5 to 15 mg/kg each; ≤ 1000 mg) are allowed if necessary, according to severity
before starting the experimental treatment.
- A stable dose of conventional disease-modifying anti-rheumatic drugs (cDMARD) within
4 weeks before enrollment if the patient is currently treated with a cDMARD
- Patients must have the ability to understand the requirements of the study, provide
written informed consent prior to participation in the study (including consent for
the use and disclosure of research-related health information) and comply with the
study protocol procedures (including required study visits)
- Patients must have an affiliation with a mode of social security (profit or being
entitled)
- An allergy or hypersensitivity to monoclonal antibodies or either of the study drugs
(rituximab, abatacept or tocilizumab) or to their excipients
- A previous treatment with a combination of rituximab plus a cDMARD, with
tofacitinib, or with tocilizumab
- A contraindication to a combination of rituximab plus a cDMARD, to tofacitinib, or
to tocilizumab (including an ongoing infection; history of recent cancer <5 years
before enrollment, except for cured non-melanoma skin cancer); pregnancy; and
breastfeeding.
- Patients with severe vasculitis manifestations that requires plasma exchange therapy
including severe renal failure with a creatinine level ≥350 µmol/L or severe
alveolar haemorrhage
- Patients with vasculitis in remission
- Patients with symptoms attributable to chronic and non-active GPA
- Patients with severe cardiac failure defined as class IV in New York Heart
Association
- Patients with acute infections or chronic active infections (including HIV, HBV or
HCV)
- Patients with active cancer or recent cancer (<5 years), except basocellular
carcinoma and prostatic cancer of low activity controlled by hormonal treatment
- Pregnant women and lactation. All women with childbearing potential are required to
have a negative serum pregnancy test before treatment and must agree to maintain
highly effective contraception from the date of consent through the end of the
study, and for women who are taking tocilizumab or tofacitinib through 3 months
after the last treatment administration, for women who are taking rituximab in
combination with methotrexate through 6 months after the last treatment
administration, for women who are taking rituximab in combination with mycofenolate
mofetil or with azathioprine through 3 months after the last treatment
administration
- Patients with other uncontrolled diseases, including drug or alcohol abuse, severe
psychiatric diseases, that could interfere with participation in the trial according
to the protocol
- Patients included in other investigational therapeutic study within the previous 3
months
- Patients suspected not to be observant to the proposed treatments
- Laboratory parameter exclusions
1. aspartate or alanine aminotransferase (AST/SGOT or ALT/SGPT) > 5 times upper
limit of normal
2. Platelet count <100.000/mm3
3. White blood cell count <2000/mm3