Wegener's GranulomatosisPhase 2NCT00530075
Phase II Study on Gusperimus in Patients With Refractory Wegener's Granulomatosis
A Phase 2 study testing Gusperimus in people with Wegener's Granulomatosis, run by Nippon Kayaku Co., Ltd. at 7 sites in 6 countries.
Trial summary
Wegener's granulomatosis is a primary systemic vasculitis characterized by granulomatous and necrotizing inflammation predominantly affecting the respiratory tract and the kidneys. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Wegener's Granulomatosis
- What is being tested?
- Gusperimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 7 sitesin 6 countries
- Study dates
- Dec 2003to Feb 2006
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Documented diagnosis of WG according to American College of Rheumatology (ACR) and Chapel Hill Consensus Conference (CHCC) definition
- BVAS >= 4
- Total disease duration >= 3 months treated with CYC or >= 6 months with MTX
- Age 18 - 80
- WBC >= 4,000/mm3, haemoglobin >= 8g/dl, neutrophils >= 2,500/mm3, platelets >= 100,000/mm3
- ALT, bilirubin and alkaline phosphatase levels within 2x the upper limits of normal
Show all 10Show fewer
- Documented to be non-pregnant by serum/urine pregnancy test
- Willing to participate in this study
- Provide signed informed consent
- Able and prepared to self-administer the study drug or have a close friend/relative able to do this
Who cannot join
- Participation in another clinical research study
- Pregnant or nursing mothers and women of childbearing age not using appropriate contraception
- Clear evidence of active disease due to bacteria/viral infection
- Patient has an unacceptable risk for participation in a study of immunosuppressive therapy
- History of substance abuse or psychotic disorders
- Previous treatment with Gusperimus
Trial locations and contacts
7 sites in 6 countries.
7 sites in 6 countries
United Kingdom2 sites
Addenbrookes Hospital
Cambridge, CB2 2QQ
Western General Hospital
Edinburgh, Scotland, EH4 2XU
About this study
Wegener's granulomatosis is a primary systemic vasculitis characterized by granulomatous and necrotizing inflammation predominantly affecting the respiratory tract and the kidneys. Conventional therapy of Wegener's granulomatosis with cyclophosphamide and corticosteroids is limited by incomplete remissions and a high relapse rate. Patients accumulate irreversible damage due to the disease and the consequences of prolonged drug exposure. The efficacy and safety of an alternative immunosuppressive drug, gusperimus, was evaluated in patients with refractory disease. A prospective, international, nulti-centre, single limb, open label study. Entry required active Wegener's granulomatosis with a Birmingham Vasculitis Activity Score (BVAS) >=4 and previous therapy with cyclophosphamide or methotrexate. Immunosuppressive drugs were withdrawn at entry and prednisolone doses adjusted according to clinical status. Gusperimus, 0.5mg/kg/day, was self-administered by subcutaneous injection in six treatment cycles of 21 days with a seven day washout between cycles. Cycles were stopped early for white blood count < 4,000/mm3. The primary endpoint was complete remission (BVAS=0 for at least 2 months) or partial remission (BVAS<50% of entry score). After the sixth cycle azathioprine was commenced and follow-up continued for a further six months.
- Conditions
- Wegener's Granulomatosis
- Being tested
- Gusperimus
- Keywords
- Wegener Granulomatosis, Vasculitis, Gusperimus, Immunosuppression
- Medical subject headings
- Granulomatosis with Polyangiitis, Vasculitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GusperimusDrug
SC, 0.5mg/kg/day, consecutive 21 days administration, 1 to 2 weeks rest, 6 cycles
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Gusperimus Receives: Drug: Gusperimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Remission of Vasculitis
The primary efficacy outcome measure was remission of vasculitis. Complete remission was defined as a Birmingham vasculitis activity score (BVAS) of 0 sustained for at least 2 months. Partial remission was defined as a reduction in BVAS of 50% or more, sustained for at least 2 months, when compared with the BVAS at entry.
Entry required active Wegener's granulomatosis with a BVAS >= 4. Their disease had to be active, as measured with BVAS in which clinical manifestations caused by active vasculitis are scored on a list of predefined organ-specific items.
Measured: At Entry (Day 1 of Cycle 1), Day 22 of cycles 1-6, up to 24 weeks
Secondary outcomes (7)
Duration of Clinical Response
Time from Complete Remission or Partial Remission to Relapse.
Measured: At Entry (Day 1 of Cycle 1), Day 22 of cycles 1-6, up to 24 weeks, End of treatment period, and 3 and 6 months of follow-up period
Haematuria
Assessment of anti-inflammatory activity of gusperimus using surrogate marker: number of hematuria-positive patients.
Measured: At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks
Creatinine
Assessment of anti-inflammatory activity of gusperimus using surrogate marker: serum creatinine level
Measured: At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks
ANCA
Assessment of anti-neutrophil cytoplasmic antibody (ANCA): Number of ANCA-positive patients was counted.
ANCA are highly associatred with active WG, with c-ANCA titres observed in 90% of WG. In addition to their diagnostic value, it has been suggested that ANCA may have a predictive value for relapse in patients with systemic vasculitis.
Measured: At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks
CRP
Assessment of anti-inflammatory activity of gusperimus using surrogate marker: serum C-reactive protein level.
Measured: At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks
Vasculitis Damage Index (VDI)
Assessment of the degree of irreversible damage due to the vasculitis using VDI scoring system. The VDI comprises 64 items of damage (grouped into 11 organ-based systems). Total VDI score is 0 - 64. The higher scores represent the more severe damage occurred in patients. The VDI score can either increase or remain the same over time.
Measured: At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks, 6 months of follow-up period
SF-36
Assessment of the impact of gusperimus on general health using the Short form-36 (SF-36) questionaire. The SF-36 is a self-report, 36 item survey measuring health-related quality-of-life. Thirty-five items are used to construct 8 scales: (1) physical functioning, (2) role physical, (3) bodily pain, (4) general health, (5) vitality, (6) social function, (7) role emotional, and (8) mental health. Raw scores are calculated as the sum of re-coded scale items and transformed to a 0 to 100 scale. If scores for all 8 scales are available, two summary measures known as component scores are derived: the Physical Health Component Score (PCS) and the Mental Health Component Score (MCS). First each scale standardized to the relevant population. Then PCS and MCS are calculated as the weighted sum of standardized scores. All scales and the component scores are positively scored so that higher scores represent better health-related quality-of-life.
Measured: At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2007 (estimated)
- Study startDec 2003
- Primary completionFeb 2006
- Study completionFeb 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Wegener's 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nippon Kayaku Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- David Jayne, Principal investigator, Cambridge University Hospitals NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00530075
- Sponsor's protocol ID
- 102
- Status last verified
- Sep 2007
- First submitted
- 14 Sep 2007
- Last updated
- 6 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Birck R, Warnatz K, Lorenz HM, Choi M, Haubitz M, Grunke M, Peter HH, Kalden JR, Gobel U, Drexler JM, Hotta O, Nowack R, Van Der Woude FJ. 15-Deoxyspergualin in patients with refractory ANCA-associated systemic vasculitis: a six-month open-label trial to evaluate safety and efficacy. J Am Soc Nephrol. 2003 Feb;14(2):440-7. doi: 10.1097/01.asn.0000048716.42876.14.
PubMed 12538745
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study on Gusperimus in Patients With Refractory Wegener's Granulomatosis
- ClinicalTrials.gov ID
- NCT00530075
- Acronym / sponsor ID
- 102
- Conditions
- Wegener's Granulomatosis
- Keywords
- Wegener Granulomatosis, Vasculitis, Gusperimus, Immunosuppression
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Nippon Kayaku Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- Dec 2003
- Primary completion
- Feb 2006 (actual)
- Study completion
- Feb 2006 (actual)
- First posted
- 17 Sep 2007 (estimated)
- Results
- Posted 6 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Wegener's granulomatosis is a primary systemic vasculitis characterized by granulomatous and necrotizing inflammation predominantly affecting the respiratory tract and the kidneys. Conventional therapy of Wegener's granulomatosis with cyclophosphamide and corticosteroids is limited by incomplete remissions and a high relapse rate. Patients accumulate irreversible damage due to the disease and the consequences of prolonged drug exposure. The efficacy and safety of an alternative immunosuppressive drug, gusperimus, was evaluated in patients with refractory disease. A prospective, international, nulti-centre, single limb, open label study. Entry required active Wegener's granulomatosis with a Birmingham Vasculitis Activity Score (BVAS) >=4 and previous therapy with cyclophosphamide or methotrexate. Immunosuppressive drugs were withdrawn at entry and prednisolone doses adjusted according to clinical status. Gusperimus, 0.5mg/kg/day, was self-administered by subcutaneous injection in six treatment cycles of 21 days with a seven day washout between cycles. Cycles were stopped early for white blood count < 4,000/mm3. The primary endpoint was complete remission (BVAS=0 for at least 2 months) or partial remission (BVAS<50% of entry score). After the sixth cycle azathioprine was commenced and follow-up continued for a further six months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: GusperimusGusperimus |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Documented diagnosis of WG according to American College of Rheumatology (ACR) and Chapel Hill Consensus Conference (CHCC) definition
- BVAS >= 4
- Total disease duration >= 3 months treated with CYC or >= 6 months with MTX
- Age 18 - 80
- WBC >= 4,000/mm3, haemoglobin >= 8g/dl, neutrophils >= 2,500/mm3, platelets >= 100,000/mm3
Key exclusion criteria (6 listed)
- Participation in another clinical research study
- Pregnant or nursing mothers and women of childbearing age not using appropriate contraception
- Clear evidence of active disease due to bacteria/viral infection
- Patient has an unacceptable risk for participation in a study of immunosuppressive therapy
- History of substance abuse or psychotic disorders
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 |
|---|---|---|
| GusperimusSC, 0.5mg/kg/day, consecutive 21 days administration, 1 to 2 weeks rest, 6 cycles | Drug | 1 |
Primary outcome
Remission of Vasculitis
Time frame: At Entry (Day 1 of Cycle 1), Day 22 of cycles 1-6, up to 24 weeks
The primary efficacy outcome measure was remission of vasculitis. Complete remission was defined as a Birmingham vasculitis activity score (BVAS) of 0 sustained for at least 2 months. Partial remission was defined as a reduction in BVAS of 50% or more, sustained for at least 2 months, when compared with the BVAS at entry. Entry required active Wegener's granulomatosis with a BVAS >= 4. Their disease had to be active, as measured with BVAS in which clinical manifestations caused by active vasculitis are scored on a list of predefined organ-specific items.
7 secondary outcomes
Duration of Clinical Response
Time frame: At Entry (Day 1 of Cycle 1), Day 22 of cycles 1-6, up to 24 weeks, End of treatment period, and 3 and 6 months of follow-up period
Haematuria
Time frame: At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks
Creatinine
Time frame: At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks
ANCA
Time frame: At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks
CRP
Time frame: At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks
Vasculitis Damage Index (VDI)
Time frame: At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks, 6 months of follow-up period
SF-36
Time frame: At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 12538745Birck R, Warnatz K, Lorenz HM, Choi M, Haubitz M, Grunke M, Peter HH, Kalden JR, Gobel U, Drexler JM, Hotta O, Nowack R, Van Der Woude FJ. 15-Deoxyspergualin in patients with refractory ANCA-associated systemic vasculitis: a six-month open-label trial to evaluate safety and efficacy. J Am Soc Nephrol. 2003 Feb;14(2):440-7. doi: 10.1097/01.asn.0000048716.42876.14.
- The European Vasculitis Study GroupLink provided by the sponsor.
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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 principal investigator
Cambridge University Hospitals NHS Foundation Trust
7 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Gusperimus in people with Wegener's Granulomatosis, run by Nippon Kayaku Co., Ltd. at 7 sites in 6 countries.
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 10 inclusion and 6 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: finished, as of the sponsor's last update on 6 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United Kingdom, Czechia, Denmark, Germany, Netherlands and 1 more country. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Remission of Vasculitis (time frame: At Entry (Day 1 of Cycle 1), Day 22 of cycles 1-6, up to 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00530075, which also lists 1 linked publication.
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 6 Mar 2017.