Clinical Study Comparing the New Immunosuppressive Drug Gusperimus With the Conventional Treatment in Wegener's Granulomatosis

NCT01446211 | Terminated Phase 3 DMC

• 2 other identifiers: NO005-NK1032011-001219-30
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of the study is to assess the efficacy (superiority testing) of gusperimus compared to conventional treatment in patients with a relapse of Wegener Granulomatosis with or without ongoing steroids, and/or immunosuppressive therapy. Further, to evaluate the safety and quality of life of gusperimus treatment compared to standard treatment in patients with relapse of Wegener Granulomatosis receiving glucocorticoids.

Conditions

Wegeners Granulomatosis

Keywords

gusperimus; Wegeners granulomatosis; relapse

Outcome Measures

Primary Outcomes (1)

• Response rate

  The primary efficacy variable is the rate of patients showing a response, with the level of disease activity Birmingham Vasculitis Activity Score (BVAS) ≤ 2, within 24 weeks of trial entry, which is maintained without relapse until the end of the trial (Week 52). The primary efficacy endpoint includes: i) Remission - defined as the complete absence of active clinical disease, i.e. a BVAS score of 0, for at least two months on a stable prednisone dose of ≤ 10 mg/day. ii) Low activity Disease State - persistence of up to two minor BVAS items (BVAS ≤ 2).

  52 weeks

Secondary Outcomes (13)

• Time to response

  From the date of study entry until the first occasion that BVAS is ≤ 2, assessed up to 52 weeks

• Response duration

  From the date of response with BVAS≤2 until relapse, assessed up to 48 weeks

• Frequency of severe relapses

  Up to 52 weeks

• Vasculitis Damage Index (VDI) score change

  12 months

• Glomerular Filtration Rate (eGFR) change

  12 months

Study Arms (2)

Test group - gusperimus

EXPERIMENTAL

Both severity subgroups (severe and non-severe) will be treated with gusperimus + glucocorticoids.

Drug: Gusperimus + glucocorticoids

Control group

ACTIVE COMPARATOR

The severe subgroup will receive a course (13 - 22 weeks) of cyclophosphamide followed by methotrexate + glucocorticoids. Patients intolerant to methotrexate and patients with impaired renal function will receive azathioprine + glucocorticoids. The non-severe subgroup will receive methotrexate + glucocorticoids(or azathioprine + glucocorticoids for those previously intolerant to methotrexate or with impaired renal function).

Drug: cyclophosphamide followed by methotrexate (azathioprine) + glucocorticoids or methotrexate (azathioprine) + glucocorticoids

Interventions

Gusperimus + glucocorticoids DRUG

Both severity subgroups will be treated with gusperimus + glucocorticoids up to 12 months.

Test group - gusperimus

cyclophosphamide followed by methotrexate (azathioprine) + glucocorticoids or methotrexate (azathioprine) + glucocorticoids DRUG

Severe subgroup: will receive intravenous cyclophosphamide pulses for at least 13 weeks and 22 weeks at maximum, followed by methotrexate + glucocorticoids after achieving a response with BVAS ≤ 2. Patients intolerant to methotrexate and patients with impaired renal function will receive azathioprine + glucocorticoids . Non-severe subgroup: will receive methotrexate + glucocorticoids (or azathioprine + glucocorticoids for those previously intolerant to methotrexate or with impaired renal function).

Control group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented diagnosis of Wegener's Granulomatosis (WG) according to the American College of Rheumatology classification criteria.
• Diagnosis of WG at least 6 months before entry and initial induction therapy with a combination of Glucocorticoids and an immunosuppressive (Cyclophosphamide or Methotrexate) or rituximab.
• Relapse of WG with or without ongoing Glucocorticoids, and/or immunosuppressive therapy with Azathioprine/Mycophenolate Mofetil/Methotrexate or Leflunomide. The minimum disease activity is defined by the presence of one new/worse major or three new/worse minor BVAS (version 3) items.
• Patients between 18 - 75 years.
• Medically acceptable and reliable contraception method during the study course. (Women should not become pregnant for at least 6 months after Cyclophosphamide treatment).
• Written informed consent for study participation given by the patient.
• Patients able and prepared to self-administer the study medication or having a relative/third person able to do it.
• Ability to read, understand and record information required by protocol

You may not qualify if:

• Other multi-system autoimmune disorders, including systemic lupus erythematosus and anti-Glomerular Basement Membrane disease.
• Systemic vasculitis due to a viral infection.
• Cyclophosphamide therapy intolerance, hypersensitivity or contraindication to Cyclophosphamide (active substance or any of the excipients) in patients with severe relapse of WG.
• Hypersensitivity or contraindication to
• Spanidin (active substance or any of the excipients) or
• both Methotrexate (active substance or any of the excipients) and Azathioprine(active substance or any of the excipients) or
• methylprednisolone, prednisolone or other corticosteroids (active substance or any of the excipients).
• Underlying medical conditions, which in the opinion of the Investigator place the patient at an unacceptable risk level for participating in a study.
• Previous randomisation in this study.
• Cyclophosphamide , intravenous immunoglobulin, anti-cytokine biologic therapies, plasma exchange or Abatacept in the three months prior to entry to the trial. Rituximab, Alemtuzumab or stem cell transplantation is not permitted in the six months prior to entry to the trial.
• Previous treatment with gusperimus.
• Participation in another clinical trial with investigational drugs within the last 3 months before screening or during the present trial period.
• Pregnant or breast-feeding females.
• Active bacterial/viral infection (Human Immunodeficiency Virus, Hepatitis B, Hepatitis C, Tuberculosis).
• Patients with Glomerular Filtration Rate (eGFR) \< 15 mL/min/1.73m2.

Sponsors & Collaborators

• Nordic Pharma SAS: lead

Study Sites (1)

Všeobecná fakultní nemocnice v Praze

Prague, 128 08, Czechia

Location

MeSH Terms

Conditions

Granulomatosis with Polyangiitis; Recurrence

Interventions

gusperimus; Glucocorticoids; Azathioprine; Methotrexate

Condition Hierarchy (Ancestors)

Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Thionucleosides; Sulfur Compounds; Organic Chemicals; Mercaptopurine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Aminopterin; Pterins; Pteridines

Study Officials

• David Jayne, MD

  Addenbrookes Hospital, Cambridge, United Kingdom

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2011
• First Posted: October 5, 2011
• Study Start: November 1, 2011
• Primary Completion: November 1, 2012
• Study Completion: January 1, 2015
• Last Updated: May 29, 2015

Record last verified: 2015-01

Locations

CZ (1)