Salvage Therapy for Patients With Inadequate Response to Standard of Care Therapy in Granulomatosis With Polyangiitis

Plain English Summary

Study of Salvage Therapy to Treat Patients With Granulomatosis With Polyangiitis is a Phase 3 clinical trial sponsored by Assistance Publique - Hôpitaux de Paris studying Granulomatosis With Polyangiitis, Anti-neutrophil Cytoplasmic Antibody-associated Vasculitis. Tests three different salvage strategies to treat patients with inadequate response to standard care therapy in Granulomatosis with Polyangiitis. For patients aged 18 and older with active clinical manifestations and inadequate response to previous standard of care therapy. Participation involves taking one of three treatments: rituximab with a cDMARD, tocilizumab, or tofacitinib, for 52 weeks. Alternatives include other treatments like glucocorticoids and cyclophosphamide or rituximab. The trial aims to enroll 42 participants.

Official Summary

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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Eligible patients are those with active Granulomatosis with Polyangiitis and an inadequate response to previous standard care therapy. Patients must be 18 years or older and have a stable dose of oral glucocorticoids. Exclusions include severe vasculitis manifestations, recent cancer, and active infections. Pregnant women and those with severe psychiatric conditions are not eligible. This trial is studying Granulomatosis With Polyangiitis, Anti-neutrophil Cytoplasmic Antibody-associated Vasculitis, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures the proportion of patients achieving remission or response, which could significantly improve patient outcomes. The specific primary outcome measures are: Proportion of patients with a response or a remission (week 12). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial aims to identify the most effective salvage therapy for patients with Granulomatosis with Polyangiitis who have not responded to standard treatments. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Granulomatosis With Polyangiitis, Anti-neutrophil Cytoplasmic Antibody-associated Vasculitis, where improved treatment options are needed.

Investor Insight

The market for treatments for Granulomatosis with Polyangiitis is growing, with this trial potentially leading to new approved therapies. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage.

Is This Trial Right for Me?

Ask your doctor if you have active Granulomatosis with Polyangiitis and have not responded to previous treatments. Participation involves taking one of three treatments for 52 weeks. This trial is currently recruiting participants. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: SINGLE
• Enrollment: 42 participants

Interventions

• DRUG: Rituximab — 375 mg/m²/week for four consecutive weeks (Week 0, 1, 2 and 3) Maintenance rituximab at a fixed dose of 500 mg will be administered at week 24 and at week 52.
• DRUG: Tocilizumab — Subcutaneous injection of 162 mg per week
• DRUG: Tofacitinib — \- Tofacitinib, administered orally at a dose of 5 mg twice a day. Tofacitinib will start at week 0. Treatment will be continued until week 52

Primary Outcomes

• Proportion of patients with a response or a remission (week 12)

Secondary Outcomes

• Proportion of patients with a response or a remission at week 26 and 52. (week 26 and 52)
• Physician's and patient's global assessment of disease activity (week 12 and 52)
• Patient-reported outcomes (week 12, 24 and 52)
• Adverse events (week 26 and 52)
• Corticosteroids use (week 26 and 52)

Full Eligibility Criteria

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)

Exclusion Criteria:

* 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

Trial Locations

• Hôpital de la Croix Saint Simon, Paris, France

Frequently Asked Questions

Related Conditions

• Related conditions include other forms of vasculitis and autoimmune diseases.
• Therapeutic areas include rheumatology and immunology.

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