Reslizumab treatment for eosinophilic granulomatosis with polyangiitis (EGPA)

Open-Label, to Evaluate the Efficacy and Safety of Reslizumab in the Treatment of Eosinophilic Granulomatosis With Polyangiitis (EGPA) Study: RITE Study

This study will try reslizumab, an anti–IL-5 antibody, in adults with EGPA to see if it helps control symptoms and reduce the need for oral steroids.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: National Jewish Health (Academic / other)
• Drugs / interventions: reslizumab, mepolizumab, lebrikizumab, methotrexate, cyclophosphamide, prednisone
• Locations: 1 site (Denver, Colorado)
• Trial ID: NCT02947945 on ClinicalTrials.gov

What this trial studies

This is an open-label Phase 2 study in which all participants receive reslizumab in addition to their usual EGPA medicines. Reslizumab is given intravenously at 3 mg/kg every four weeks for seven doses (28 weeks of treatment), and participants are followed across 11 visits over a 44-week period. Study staff will call participants every two weeks to review symptoms, medication use, and any steroid tapering. Safety, steroid-sparing effects, and clinical status will be monitored with standard tests and questionnaires.

Who should consider this trial

Good fit: Adults (≥18 years) with EGPA for at least 6 months who have eosinophilia (>1.0 x10^9/L or >10% of leukocytes) plus at least two other EGPA features (for example biopsy evidence, neuropathy, nonfixed pulmonary infiltrates, sino-nasal disease, or cardiomyopathy).

Not a fit: Patients without significant eosinophilia, those already well controlled without steroids, or those unable to attend regular IV infusion visits may be unlikely to benefit from this study.

Why it matters

Potential benefit: If successful, reslizumab could reduce steroid use and decrease EGPA flares, improving symptoms and lowering steroid-related side effects.

How similar studies have performed: Other IL-5 blocking drugs, notably mepolizumab, have shown steroid-sparing benefit in EGPA, but reslizumab itself has been less extensively studied in this condition.

Eligibility criteria

Inclusion Criteria:

* Informed Consent: Able to give written informed consent prior to participation in the study, which will include the ability to comply with the requirements and restrictions listed in the consent form. Subjects must be able to read, comprehend, and write at a level sufficient to complete study related materials.
* Gender and Age: Male or female subjects \>18 years old
* EGPA diagnosis: subjects who have been diagnosed with EGPA for at least 6 months based on the history or presence of: asthma plus eosinophilia (\>1.0x109/L and/or \>10% of leucocytes) plus at least two of the following additional features of EGPA:

  * A biopsy showing histopathological evidence of eosinophilic vasculitis, or perivascular eosinophilic infiltration, or eosinophil-rich granulomatous inflammation;
  * Neuropathy, mono or poly (motor deficit or nerve conduction abnormality);
  * Pulmonary infiltrates, non-fixed;
  * Sino-nasal abnormality;
  * Cardiomyopathy (established by echocardiography or MRI);
  * Glomerulonephritis (haematuria, red cell casts, proteinuria);
  * Alveolar haemorrhage (by bronchoalveolar lavage);
  * Palpable purpura;
  * ANCA positive (MPO or PR3).
* Subjects who have received a cyclophosphamide (CYC) induction regimen may be included a minimum of 2 weeks after the last dose of daily oral CYC, or 3 weeks after the last dose of pulsed IV CYC prior to visit 1, if their total WBC is ≥4x109/L prior to visit 1.
* Subjects who have received a methotrexate, azathioprine, or mycophenolate mofetil induction regimen may be included if on a stable dose for at least 4 weeks prior to visit 1.
* Corticosteroid therapy: Subject must be on a stable dose of oral prednisolone or prednisone of ≥5 mg/day for at least 4 weeks prior to visit 1.
* Immunosuppressive therapy: If receiving immunosuppressive therapy (including methotrexate, azathioprine, or mycophenolate mofetil, but excluding restricted medications below) the dosage must be stable for the 4 weeks prior to visit 1 and during the study (dose reductions for safety reasons will be permitted).
* Female subjects: To be eligible for entry into the study, females of childbearing potential (FCBP) must commit to consistent and correct use of an acceptable method of birth control beginning with consent, for the duration of the trial.

Exclusion Criteria:

* Hypereosinophilic Syndrome
* Wegener's Granulomatosis
* Malignancy
* Parasitic disease
* Pregnant or nursing
* If female and of child-bearing potential, must have negative pregnancy test and must adhere to acceptable method of contraception (with \<1% failure rate) during the study and for four months after the study.
* Any other medical illness that precludes study involvement
* Patients who are currently receiving or have previously received reslizumab or any other type of anti-interleukin therapy (i.e. mepolizumab, lebrikizumab etc.) within the last three months.
* Taking cyclophosphamide
* Any patients with a known hypersensitivity to reslizumab or any of its excipients

Where this trial is running

Denver, Colorado

• National Jewish Health — Denver, Colorado, United States (Recruiting)

Study contacts

• Principal investigator: Michael Wechsler, MD — National Jewish Health
• Study coordinator: Michael Wechsler, MD

Conditions Asthma