Wegeners GranulomatosisPhase 3SPARROWNCT01446211
Clinical Study Comparing the New Immunosuppressive Drug Gusperimus With the Conventional Treatment in Wegener's Granulomatosis
A Phase 3 study testing Gusperimus + glucocorticoids and cyclophosphamide followed by methotrexate (azathioprine) + glucocorticoids or methotrexate (azathioprine) + glucocorticoids in people with Wegeners Granulomatosis, run by Nordic Pharma SAS at 1 site in Czechia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Wegeners Granulomatosis
- What is being tested?
- Gusperimus + glucocorticoids and cyclophosphamide followed by methotrexate (azathioprine) + glucocorticoids or methotrexate (azathioprine) + glucocorticoids
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteCzechia
- Study dates
- Nov 2011to Jan 2015
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 17Show fewer
- 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.
- Alanine transaminase (ALT), Aspartate aminotransferase (AST), bilirubin, and Alkaline phosphatase (ALP) levels above 2 x the upper normal limit.
- Inadequate bone-marrow function: White Blood Cells (WBC) < 4000/mm3, haemoglobin < 8 g/dL, neutrophils < 2500/mm3, platelets < 100 000/mm3.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomised, Evaluator-Blinded, Multicentre, International, Parallel-Group, Active-Controlled Clinical Trial of Gusperimus Versus Conventional Therapy in Relapse of Granulomatosis With Polyangiitis (Wegener's Granulomatosis) SPARROW Study - SPAnidin in Relapsing GRanulomatosis With POlyangiitis Wegener's Granulomatosis)
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.
Read the detailed description
Wegener Granulomatosis without treatment is life-threatening. The standard treatment with corticosteroids and cyclophosphamide is usually effective at controlling active disease. However, disease relapse is frequent and requires increased exposure to these toxic drugs. In other patients initiation or continuation of these standard drugs is contraindicated due to intolerable side effects. No well-established therapy is available for relapsing patients. They may suffer severe organ damage due to progressive disease, or may die. The proposed indication for gusperimus is the treatment of relapsing Wegener Granulomatosis. The aim of therapy with gusperimus is to induce and maintain remission thereby avoiding further cyclophosphamide and reducing corticosteroid exposure.
- Conditions
- Wegeners Granulomatosis
- Being tested
- Gusperimus + glucocorticoids, cyclophosphamide followed by methotrexate (azathioprine) + glucocorticoids or methotrexate (azathioprine) + glucocorticoids
- Keywords
- gusperimus, Wegeners granulomatosis, relapse
- Medical subject headings
- Granulomatosis with Polyangiitis, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gusperimus + glucocorticoidsDrug
Both severity subgroups will be treated with gusperimus + glucocorticoids up to 12 months.
cyclophosphamide followed by methotrexate (azathioprine) + glucocorticoids or methotrexate (azathioprine) + glucocorticoidsDrug
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).
| Study group | Role | What they receive |
|---|---|---|
| Test group - gusperimus | Experimental | Both severity subgroups (severe and non-severe) will be treated with gusperimus + glucocorticoids. Receives: 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). Receives: Drug: cyclophosphamide followed by methotrexate (azathioprine) + glucocorticoids or methotrexate (azathioprine) + glucocorticoids |
What is being measured
The primary outcome is the main question the study is designed to answer.
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:
- 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).
Measured: 52 weeks
Secondary outcomes (13)
Time to response
Time to response (response is defined as the time from study entry to the first occasion that BVAS is ≤ 2, and there has been adherence to the steroid reduction protocol)
Measured: From the date of study entry until the first occasion that BVAS is ≤ 2, assessed up to 52 weeks
Response duration
Response duration defined as time from response with BVAS≤2 to relapse (relapse is defined as the return or first occurrence of one major and/or three minor BVAS items)
Measured: From the date of response with BVAS≤2 until relapse, assessed up to 48 weeks
Frequency of severe relapses
Frequency of severe relapses (defined as at least one major BVAS item)
Measured: Up to 52 weeks
Vasculitis Damage Index (VDI) score change
VDI score change from baseline to month 12
Measured: 12 months
Glomerular Filtration Rate (eGFR) change
eGFR change from baseline to month 12 in all patients and in a subgroup defined as having a baseline eGFR ≤ 60mL/min (i.e. renal impairment at baseline)
Measured: 12 months
Frequency of Adverse Events (AEs) and Serious Adverse Event (SAEs)
Frequency of AEs and SAEs. (Total number of AEs per group according to AE category) (Percentage of patients in each group with a severe AE)
Measured: Up to 52 weeks
Frequency of severe infection
Frequency of severe infection (a severe infection is defined as an infection that requires intravenous antibiotics or hospitalisation).(Percentage of patients in each group with a severe infection)
Measured: Up to 52 weeks
Pharmacokinetic parameters at selected sites
Pharmacokinetic parameters Area Under the plasmaconcentration - time Curve (AUC), Maximum concentration reached in plasma (Cmax), Time to maximum concentration reached in plasma (Tmax) and Elimination half life in plasma (T½) calculated from the measured plasma samples collected at regular time intervals after administration of gusperimus on the first day of three treatment cycles
Measured: 1st day of gusperimus cycles 1, 6 or 7, 12 or 13
Short-Form-36 (SF-36)
Pooled physical and mental SF-36 domains change from baseline to month 6
Measured: 6 months
Short-Form-36 (SF-36)
Pooled physical and mental SF-36 domains change from baseline to month 12
Measured: 12 months
Total corticosteroid exposure
The total corticosteroid exposure
Measured: Up to 52 weeks
Questionnaire EQ-5D
Change in EQ-5D between baseline and month 12
Measured: 12 months
Frequency of non-severe relapses
Frequency of non-severe relapses (defined as at least 3 minor BVAS items with no major BVAS items).
Measured: Up to 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2011 (estimated)
- Study startNov 2011
- Primary completionNov 2012
- Study completionJan 2015
Why it stopped: Change of design consideration
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Wegeners GranulomatosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nordic Pharma SAS
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- David Jayne, MD, Principal investigator, Addenbrookes Hospital, Cambridge, United Kingdom
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01446211
- Sponsor's protocol ID
- NO005-NK103
- Other IDs
- 2011-001219-30
- Acronym
- SPARROW
- Status last verified
- Jan 2015
- First submitted
- 20 Sep 2011
- Last updated
- 29 May 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomised, Evaluator-Blinded, Multicentre, International, Parallel-Group, Active-Controlled Clinical Trial of Gusperimus Versus Conventional Therapy in Relapse of Granulomatosis With Polyangiitis (Wegener's Granulomatosis) SPARROW Study - SPAnidin in Relapsing GRanulomatosis With POlyangiitis Wegener's Granulomatosis)
- ClinicalTrials.gov ID
- NCT01446211
- Acronym / sponsor ID
- SPARROW / NO005-NK103
- Conditions
- Wegeners Granulomatosis
- Keywords
- gusperimus, Wegeners granulomatosis, relapse
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Change of design consideration
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Nordic Pharma SASIndustry (pharma, biotech, devices)
- Study start
- Nov 2011
- Primary completion
- Nov 2012 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 5 Oct 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Wegener Granulomatosis without treatment is life-threatening. The standard treatment with corticosteroids and cyclophosphamide is usually effective at controlling active disease. However, disease relapse is frequent and requires increased exposure to these toxic drugs. In other patients initiation or continuation of these standard drugs is contraindicated due to intolerable side effects. No well-established therapy is available for relapsing patients. They may suffer severe organ damage due to progressive disease, or may die. The proposed indication for gusperimus is the treatment of relapsing Wegener Granulomatosis. The aim of therapy with gusperimus is to induce and maintain remission thereby avoiding further cyclophosphamide and reducing corticosteroid exposure.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Test group - gusperimus | Experimental | Drug: Gusperimus + glucocorticoidsBoth severity subgroups (severe and non-severe) will be treated with gusperimus + glucocorticoids. |
| Control group | Active comparator | Drug: cyclophosphamide followed by methotrexate (azathioprine) + glucocorticoids or methotrexate (azathioprine) + glucocorticoidsThe 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). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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).
Key exclusion criteria (17 listed)
- 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
- Underlying medical conditions, which in the opinion of the Investigator place the patient at an unacceptable risk level for participating in a study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Gusperimus + glucocorticoidsBoth severity subgroups will be treated with gusperimus + glucocorticoids up to 12 months. | Drug | Test group - gusperimus |
| cyclophosphamide followed by methotrexate (azathioprine) + glucocorticoids or methotrexate (azathioprine) + glucocorticoidsSevere 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). | Drug | Control group |
Primary outcome
Response rate
Time frame: 52 weeks
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).
13 secondary outcomes
Time to response
Time frame: From the date of study entry until the first occasion that BVAS is ≤ 2, assessed up to 52 weeks
Response duration
Time frame: From the date of response with BVAS≤2 until relapse, assessed up to 48 weeks
Frequency of severe relapses
Time frame: Up to 52 weeks
Vasculitis Damage Index (VDI) score change
Time frame: 12 months
Glomerular Filtration Rate (eGFR) change
Time frame: 12 months
Frequency of Adverse Events (AEs) and Serious Adverse Event (SAEs)
Time frame: Up to 52 weeks
Frequency of severe infection
Time frame: Up to 52 weeks
Pharmacokinetic parameters at selected sites
Time frame: 1st day of gusperimus cycles 1, 6 or 7, 12 or 13
Short-Form-36 (SF-36)
Time frame: 6 months
Short-Form-36 (SF-36)
Time frame: 12 months
Total corticosteroid exposure
Time frame: Up to 52 weeks
Questionnaire EQ-5D
Time frame: 12 months
Frequency of non-severe relapses
Time frame: Up to 52 weeks
Results and safety
The study was stopped early (reason given: Change of design consideration). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Jayne, MD principal investigator
Addenbrookes Hospital, Cambridge, United Kingdom
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Gusperimus + glucocorticoids and cyclophosphamide followed by methotrexate (azathioprine) + glucocorticoids or methotrexate (azathioprine) + glucocorticoids in people with Wegeners Granulomatosis, run by Nordic Pharma SAS at 1 site in Czechia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 29 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Czechia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Change of design consideration). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response rate (time frame: 52 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 May 2015.