Study on Rituximab, Tocilizumab, and Tofacitinib for Patients with Granulomatosis with Polyangiitis Not Responding to Standard Therapy

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What is this study about?

This clinical trial is focused on studying treatments for a condition called Granulomatosis with Polyangiitis (GPA), which is a rare disease that causes inflammation of blood vessels. The study is designed for patients who have not responded well to standard treatments, which typically include a combination of medications like glucocorticoids and cyclophosphamide or glucocorticoids and rituximab. The purpose of the study is to find the most effective treatment strategy for these patients.

The trial will explore three different treatment approaches. The first approach involves using rituximab together with another type of medication known as a conventional disease-modifying antirheumatic drug (cDMARD), which could be methotrexate, azathioprine, or mycophenolate mofetil, with a preference for methotrexate. The second approach uses tocilizumab, and the third approach involves tofacitinib. These treatments will be compared to see which is most effective in helping patients achieve remission, which means the disease is no longer active.

Participants in the study will receive one of these treatments for up to 52 weeks. The study will monitor how well each treatment works in reducing disease activity and helping patients feel better. The trial will also look at how patients and doctors assess the disease’s activity and any side effects that may occur. The goal is to determine which treatment offers the best chance of remission for patients with GPA who have not responded to previous therapies.

1 enrollment

Upon joining the study, eligibility is confirmed based on specific criteria, including age, diagnosis, and previous treatment response.

Written informed consent is required to participate in the study.

2 initial assessment

An initial assessment is conducted to evaluate the current state of the disease and establish a baseline for future comparisons.

This includes a review of medical history and current symptoms.

3 treatment allocation

Participants are assigned to one of three treatment strategies based on the study design.

The options include: a combination of rituximab with a conventional disease-modifying antirheumatic drug (cDMARD) such as methotrexate, azathioprine, or mycophenolate mofetil; tocilizumab; or tofacitinib.

4 treatment administration

The treatment is administered according to the assigned strategy.

Rituximab is given intravenously, while methotrexate, azathioprine, and mycophenolate mofetil are taken orally.

Tocilizumab is administered via subcutaneous injection, and tofacitinib is taken orally.

5 monitoring and follow-up

Regular monitoring is conducted to assess the response to treatment and any side effects.

Follow-up visits occur at specified intervals, including weeks 12, 24, and 52, to evaluate disease activity and patient-reported outcomes.

6 evaluation of outcomes

The primary outcome is assessed at 12 weeks, focusing on the proportion of patients achieving a response or remission.

Secondary outcomes include assessments at weeks 24 and 52, comparing disease activity and patient-reported outcomes over time.

Who Can Join the Study?

Patients must have been newly diagnosed or have a relapsing condition called granulomatosis with polyangiitis (GPA) according to specific criteria set in 2022.
Patients must be aged 18 years or older.
Patients must have active symptoms that are due to GPA.
Patients must have had an inadequate response to previous standard treatments, which include either:
- A combination of glucocorticoids (a type of steroid) plus cyclophosphamide (a medication used to suppress the immune system).
- AND/OR a combination of glucocorticoids plus rituximab (a medication that targets certain immune cells).
An inadequate response to treatment is defined as:
- The disease getting worse despite 12 weeks of standard treatment.
- Or not having at least a 50% reduction in disease activity after 12 weeks of treatment.
- Or having ongoing active disease that requires continuing corticosteroids at a dose of more than 7.5 mg/day of prednisone (a type of steroid) after 12 weeks of treatment.
Patients must be on a stable dose of oral glucocorticoids of at least 7.5 mg/day of equivalent prednisone for the 4 weeks before joining the study. Short-term high doses of methylprednisolone (another steroid) are allowed if needed due to the severity of the condition before starting the study treatment.
If patients are currently treated with conventional disease-modifying anti-rheumatic drugs (cDMARD), they must be on a stable dose for 4 weeks before joining the study.
Patients must be able to understand the study requirements, provide written consent to participate, and agree to follow the study procedures, including attending required study visits.
Patients must have some form of social security or be entitled to it.

Who Cannot Join the Study?

Patients who have not had an inadequate response to standard treatments for their condition. This means if the usual treatments are working well for you, you cannot participate.
Patients who are not diagnosed with granulomatosis with polyangiitis (GPA). This study is only for those with this specific condition.
Patients who are not within the age range specified for the study. The study has specific age requirements that must be met.
Patients who are part of a vulnerable population. This means if you are in a group that needs special protection, you may not be eligible.
Patients who are not able to follow the study procedures or attend the required visits. This means if you cannot commit to the study schedule, you cannot participate.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country
Groupe Hospitalier Du Sud Ile De France	Melun	France
Centre Hospitalier Universitaire De Bordeaux	Bordeaux	France
Centre Hospitalier Regional Et Universitaire De Brest	Brest	France
Oncopole Claudius Regaud	Toulouse	France
Aix Marseille University	Marseille	France
CHU Grenoble Alpes	La Tronche	France

Other Sites

Site Name	City	Country
Centre Hospitalier De Perpignan	Perpignan	France
Centre Hospitalier De Valenciennes	Valenciennes	France
Hopital Europeen Marseille	Marseille	France
Centre Hospitalier De Niort	Niort	France
Fondation A De Rothschild	Paris	France
Centre Hospitalier Le Mans	Le Mans	France
Centre Hospitalier Universitaire De Montpellier	Montpellier	France
Centre Hospitalier Universitaire De Nantes	Nantes	France
Hopitaux Prives De Metz	Vantoux	France
Centre Hospitalier Universitaire Amiens Picardie	Amiens	France
Centre Hospitalier De Dax	Dax	France
Groupe Hospitalier Diaconesses Croix Saint Simon	Paris	France
Centre Hospitalier Lyon Sud	Pierre Benite	France
Hopital Beaujon	Clichy	France
Hvjbpsd Esncevt &skxwfl Cxe df Cjivdnacxpufyhqn	Clermont Ferrand	France
Hpfyqhg Gmccdgd Mvhwdjjn	Clermont Ferrand	France
Cnt ddlnnvbcedtgly	Epagny Metz Tessy	France
Caqxum Hmwprtqfgts Uwoyplpvahepn Dw Dkygu	Dijon	France
Arfodtwcve Phtxtgsj Hekxvqsq Dv Mfydnnbsu	Marseille	France
Cphmqd Huvbhtjbwok Rbhmrzoe Ugbjvhtbpbnyz Dw Tfolb	Tours	France
Chsz Dh Nirza	Vandoeuvre Les Nancy	France
Clrmsa Hbwbxolagar Rsypjzku Dlywmetvlkhxyh	Angers	France
Homuxyxk Uwdkfyfkkrnspc Shiqhxvywj &frgwgj Htwuyew dm Hytkillmguc	STRASBOURG, Alsace	France

Trial status

Country	Status	Recruitment Start
France	Not yet recruiting	06.01.2025

Trial locations

Investigated drugs:

Rituximab: This medication is used in combination with other drugs to help manage granulomatosis with polyangiitis. It works by targeting specific cells in the immune system to reduce inflammation and help control the disease.

Methotrexate: Often used alongside rituximab, this medication helps to suppress the immune system and reduce inflammation. It is a conventional disease-modifying antirheumatic drug (cDMARD) that can help manage symptoms and prevent disease progression.

Azathioprine: Another cDMARD that may be used with rituximab, azathioprine helps to lower the activity of the immune system, reducing inflammation and helping to control the disease.

Mycophenolate mofetil: This medication can also be combined with rituximab. It works by suppressing the immune system to help reduce inflammation and manage the symptoms of granulomatosis with polyangiitis.

Tocilizumab: This medication is used to help control inflammation by blocking a specific protein in the body that contributes to the immune response. It is considered as one of the potential therapies for patients who do not respond adequately to standard treatments.

Tofacitinib: This medication works by interfering with the activity of certain enzymes in the immune system, helping to reduce inflammation and manage symptoms in patients with granulomatosis with polyangiitis.

Investigated diseases:

Granulomatosis with polyangiitis

Granulomatosis with Polyangiitis – This is a rare disease characterized by inflammation of the blood vessels, which can lead to damage in various organs, particularly the respiratory tract and kidneys. The disease often begins with symptoms like sinusitis, nosebleeds, or a persistent cough. As it progresses, it can cause more severe symptoms such as kidney dysfunction, skin rashes, and joint pain. The inflammation is due to an abnormal immune response, which can result in the formation of granulomas, or small areas of inflammation. Over time, the disease can lead to significant organ damage if not managed properly. The progression and symptoms can vary widely among individuals, making it a complex condition to understand and manage.

Trial ID:

2024-516687-28-00

Protocol code:

APHP200026

NCT ID:

NCT04871191

Trial Phase:

Therapeutic confirmatory (Phase III)

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Study on Rituximab, Tocilizumab, and Tofacitinib for Patients with Granulomatosis with Polyangiitis Not Responding to Standard Therapy

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?