MAINEPSAN : A Prospective Comparative Randomized Double-blind Placebo-controlled In-Parallel Groups Multicenter, Study to Evaluate the remission MAINtenance using Extended administration of Prednisone in Systemic anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Hospices Civils De Lyon

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Phenomena and Processes [G] - Immune system processes [G12]

Trial duration

20 Aug 2019 → ongoing

Decision date (initial)

2024-06-17

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-514156-33-00

EudraCT number

2018-001215-69

ClinicalTrials.gov

NCT03290456

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

Relapse rate of patients continuing low-dose prednisone treatment until 13 months of treatment (Visit M13) versus those who will have prednisone treatment cessation after one month (visit M1), on remission maintenance with rituximab therapy, after achievement of remission of GPA or MPA, defined as patients maintaining a BVAS (Birmingham Vasculitis Activity Score)=0 at Month 30

Secondary objectives 7

1. To compare the rate of AE and SAE between Day 1 and Month 30,
2. To compare the rate of predefined severe events related to glucocorticoids between Day 1 and Month 30 including osteoporotic fracture and weight gain,
3. To compare the duration of complete remission, defined as the total accrued duration in weeks with BVAS=0 between Day 1 and Month 30,
4. To compare the rate of minor and major vasculitis relapse at Month 30,
5. To compare the side effect related to low dose prednisone by GTI toxicity scale between Day 1 and Month 30,
6. To compare the prednisone use between Day 1 and Month 30,
7. To compare the number of deaths between Day 1 and Month 30,

Conditions and MedDRA coding

Patients in remission for granulomatosis with polyangiitis (GPA, Wegener's) or microscopic polyangiitis (MPA) achieved with rituximab or cyclophosphamide or methotrexate

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Patients who has been informed about the study and has given his/her written informed consent prior to participation in the study
2. Patients with newly-diagnosed or relapsing MPA or GPA according to the ACR 1990 criteria and/or revised Chapel Hill Consensus Conference definition, independently of ANCA status
3. Patients aged of 18 years or older,
4. Patients in remission (BVAS=0) for MPA or GPA achieved with rituximab, cyclophosphamide, or methotrexate,
5. Patients who will all have already received glucocorticoids for 12 and 36 months ± 8 weeks after diagnosis or last flare before Day 1 for patients treated according the MAINRITSAN and MAINRITSAN3 protocols, respectively.
6. At Inclusion visit day, patient must be between 5 and 10 mg/day prednisone and at randomization visit day (D1), patient must be at 5 mg/day prednisone
7. Patients having received 500 mg low-dose rituximab maintenance infusion at remission achievement, according to the MAINRITSAN and MAINRITSAN3 trials

Exclusion criteria 18

1. Patients with GPA or MPA if glucocorticoids treatment has been increased > 10 mg/day for vasculitis flare or stopped during maintenance therapy
2. Patients with EGPA, or other vasculitides, defined by the ACR criteria and/or the Chapel Hill Consensus Conference
3. Patients with vasculitis with active disease defined as a BVAS >0,
4. Patients with acute infections including Sars COVID-19 or chronic active infections (including HIV, HBV or HCV)
5. Patients with active cancer or recent cancer (<5 years) or myelodysplasia, except basocellular carcinoma and low activity prostatic cancer controlled by hormonal treatment
6. Pregnant women and lactation. Patients with childbearing potential should have reliable contraception for the total duration of the study
7. Patients with contraindication to use rituximab
8. 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,
9. Patients included in other investigational therapeutic study within the previous 3 months excepted for the PNEUMOVAS trial.
10. Patients suspected not to be observant to the proposed treatments
11. Patients who have neutrophils cell count ≤1.500 /mm3,
12. Patients who have platelet count ≤100,000/mm3,
13. Patients with severe hypogammaglobulinemia (invasive bacterial or fungal infection with IgG < 5 g/L or IgG < 3 g/L in patients without infection)
14. Patients who have ALT or AST or GGT or PAL level greater than 3 times the upper limit of normal or total bilirubin level greater than 2 times the upper limit of normal that cannot be attributed to underlying MPA-GPA disease,
15. Patients unable to give written informed consent prior to study participation.
16. Patients under judicial protection,
17. Patient not affiliated to a social security scheme or other social protection scheme,
18. Patients who did not get vaccinated of covid-19 according to national recommendations.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. relapse-free survival at Month 30 (18 months after last rituximab maintenance infusion), relapse being defined as BVAS >0.

Secondary endpoints 8

1. Proportion of patients with at least one AE between Day 1 and Month 30,
2. Percentage of patients with at least one minor or major vasculitis flare (BVAS>0) or one predefined severe event corresponding to AE of grade 3 to 5 of the Common Terminology Criteria, including severe side effect related to glucocorticoids (infection requiring hospitalization or intravenous antibiotics, osteoporotic fracture, diabetes requiring medication, cardiovascular event, osteonecrosis, psychiatric or mood disorder requiring drug administration, weight gain >10 kg), between D1 and M30
3. Percentage of patients with at least one SAE between Day 1 and Month 30 corresponding to any AE that results in death, is life-threatening, requires inpatient hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability/incapacity or congenital anomaly/birth defect or any other AE considered "medically significant",
4. Percentage of patients with minor (reappearance or worsening of disease with a BVAS >0, not corresponding to a major relapse but requiring mild treatment intensification) or major vasculitis (occurrence or new onset of potentially organ- or life-threatening disease activity that cannot be treated with an increase of glucocorticoids alone and requires further escalation of treatment) between Day 1 and Month 30 (BVAS >0) and time to first vasculitis relapse,
5. Variation of GTI toxicity score between Day 1 and Month 30,
6. Prednisone area under the curve of administrated dose between Day 1 and Month 30,
7. Number of deaths, whatever the cause at Month 30,
8. Variation of the bone mineral density between Day 1 and Month 30,

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Hospices Civils De Lyon

Sponsor organisation

Hospices Civils De Lyon

Address

3 Quai Des Celestins, Bp 2251 Bp 2251

City

Lyon Cedex 02

Postcode

69229

Country

France

Scientific contact point

Organisation

Hospices Civils De Lyon

Contact name

Pr Jean-Christophe Lega

Public contact point

Organisation

Hospices Civils De Lyon

Contact name

Pr Jean-Christophe Lega

Locations

1 EU/EEA country · 52 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications