Trial Outcomes & Findings for Phase II Study on Gusperimus in Patients With Refractory Wegener's Granulomatosis (NCT NCT00530075)

NCT ID: NCT00530075

Last Updated: 2017-03-06

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 45 participants
• Primary outcome timeframe: At Entry (Day 1 of Cycle 1), Day 22 of cycles 1-6, up to 24 weeks
• Results posted on: 2017-03-06

Participant Flow

The study was conducted at 7 sites in 6 European countries from 2003 to 2006

Participant milestones

Measure	Gusperimus SC, 0.5mg/kg/day, consecutive 21 days administration, 7 days rest, 6 cycles
Overall Study STARTED	45
Overall Study COMPLETED	38
Overall Study NOT COMPLETED	7

Reasons for withdrawal

Measure	Gusperimus SC, 0.5mg/kg/day, consecutive 21 days administration, 7 days rest, 6 cycles
Overall Study Adverse Event	1
Overall Study Death	1
Overall Study Lack of Efficacy	3
Overall Study Protocol Violation	1
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Phase II Study on Gusperimus in Patients With Refractory Wegener's Granulomatosis

Baseline characteristics by cohort

Measure	Gusperimus n=45 Participants SC, 0.5mg/kg/day, consecutive 21 days administration, 7 days rest, 6 cycles
Age, Continuous	51 Years n=5 Participants
Gender Female	16 Participants n=5 Participants
Gender Male	29 Participants n=5 Participants
Region of Enrollment Europe	45 participants n=5 Participants

PRIMARY outcome

Timeframe: At Entry (Day 1 of Cycle 1), Day 22 of cycles 1-6, up to 24 weeks

Population: Efficacy Population

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.

Outcome measures

Measure	Gusperimus n=44 Participants SC, 0.5mg/kg/day, consecutive 21 days administration, 7 days rest, 6 cycles
Remission of Vasculitis	95 Percentage of participants

SECONDARY outcome

Timeframe: 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

Population: Patients who had relapsed after achieved at least partial remission

Time from Complete Remission or Partial Remission to Relapse.

Outcome measures

Measure	Gusperimus n=18 Participants SC, 0.5mg/kg/day, consecutive 21 days administration, 7 days rest, 6 cycles
Duration of Clinical Response	170 Days Interval 44.0 to 316.0

SECONDARY outcome

Timeframe: At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks

Population: Efficacy population

Assessment of anti-inflammatory activity of gusperimus using surrogate marker: number of hematuria-positive patients.

Outcome measures

Measure	Gusperimus n=44 Participants SC, 0.5mg/kg/day, consecutive 21 days administration, 7 days rest, 6 cycles
Haematuria At Entry	16 Number of participants
Haematuria End of treatment period	6 Number of participants

SECONDARY outcome

Timeframe: At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks

Population: Efficacy population

Assessment of anti-inflammatory activity of gusperimus using surrogate marker: serum creatinine level

Outcome measures

Measure	Gusperimus n=44 Participants SC, 0.5mg/kg/day, consecutive 21 days administration, 7 days rest, 6 cycles
Creatinine At Entry	130 micromol/L Interval 58.0 to 299.0
Creatinine End of treatment period	132 micromol/L Interval 72.0 to 279.0

SECONDARY outcome

Timeframe: At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks

Population: Efficacy Population

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.

Outcome measures

Measure	Gusperimus n=44 Participants SC, 0.5mg/kg/day, consecutive 21 days administration, 7 days rest, 6 cycles
ANCA At Entry	39 Number of participants
ANCA End of treatment period	34 Number of participants

SECONDARY outcome

Timeframe: At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks

Population: Patients who had elevated CRP level (\> 6 mg/dL) at entry

Assessment of anti-inflammatory activity of gusperimus using surrogate marker: serum C-reactive protein level.

Outcome measures

Measure	Gusperimus n=23 Participants SC, 0.5mg/kg/day, consecutive 21 days administration, 7 days rest, 6 cycles
CRP At Entry	17.5 mg/dL Interval 7.0 to 88.0
CRP End of treatment period	9 mg/dL Interval 1.0 to 124.0

SECONDARY outcome

Timeframe: At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks, 6 months of follow-up period

Population: Efficacy Population

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.

Outcome measures

Measure	Gusperimus n=44 Participants SC, 0.5mg/kg/day, consecutive 21 days administration, 7 days rest, 6 cycles
Vasculitis Damage Index (VDI) At Entry	4.5 Score on a scale Interval 0.0 to 14.0
Vasculitis Damage Index (VDI) End of treatment period	5 Score on a scale Interval 0.0 to 16.0
Vasculitis Damage Index (VDI) 6 months of follow-up period	5 Score on a scale Interval 0.0 to 16.0

SECONDARY outcome

Timeframe: At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks

Population: Efficacy Population

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.

Outcome measures

Measure	Gusperimus n=44 Participants SC, 0.5mg/kg/day, consecutive 21 days administration, 7 days rest, 6 cycles
SF-36 Physical component score (at Entry)	29.6 Score on a scale Interval 14.8 to 50.2
SF-36 Physical component score (at End of treatment peri	34.3 Score on a scale Interval 11.6 to 53.7
SF-36 Mental component score (at Entry)	49.4 Score on a scale Interval 21.0 to 62.9
SF-36 Mental component score (at End of treatment period	48 Score on a scale Interval 23.7 to 62.8

Adverse Events

Gusperimus

Serious events: 17 serious events

Other events: 45 other events

Deaths: 0 deaths

Serious adverse events

Measure	Gusperimus n=45 participants at risk SC, 0.5mg/kg/day, consecutive 21 days administration, 7 days rest, 6 cycles
Blood and lymphatic system disorders Leucopaenia/Anaemia	15.6% 7/45 • Throughout study period, up to 24 weeks
Infections and infestations Infections	15.6% 7/45 • Throughout study period, up to 24 weeks
Infections and infestations Bronchopneumonia	11.1% 5/45 • Throughout study period, up to 24 weeks
Infections and infestations Dental abscess	2.2% 1/45 • Throughout study period, up to 24 weeks
Infections and infestations Campylobacter jejuni diarrhoea	2.2% 1/45 • Throughout study period, up to 24 weeks
Respiratory, thoracic and mediastinal disorders Relapses of Wegener's granulomatosis	8.9% 4/45 • Throughout study period, up to 24 weeks
Respiratory, thoracic and mediastinal disorders Acute upper airway obstruction	4.4% 2/45 • Throughout study period, up to 24 weeks
Respiratory, thoracic and mediastinal disorders Active Wegener's granulomatosis	2.2% 1/45 • Throughout study period, up to 24 weeks
Gastrointestinal disorders Food poisoning	2.2% 1/45 • Throughout study period, up to 24 weeks
Gastrointestinal disorders Diarrhoea	2.2% 1/45 • Throughout study period, up to 24 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	2.2% 1/45 • Throughout study period, up to 24 weeks

Other adverse events

Measure	Gusperimus n=45 participants at risk SC, 0.5mg/kg/day, consecutive 21 days administration, 7 days rest, 6 cycles
Blood and lymphatic system disorders Anaemia	17.8% 8/45 • Throughout study period, up to 24 weeks
Blood and lymphatic system disorders Leucopaenia	37.8% 17/45 • Throughout study period, up to 24 weeks
Infections and infestations Lower respiratory tract infection	26.7% 12/45 • Throughout study period, up to 24 weeks
Infections and infestations Upper respiratory tract infection	20.0% 9/45 • Throughout study period, up to 24 weeks
Infections and infestations Urinary tract infection	13.3% 6/45 • Throughout study period, up to 24 weeks
Infections and infestations Candida infection	15.6% 7/45 • Throughout study period, up to 24 weeks
General disorders Injection site pain/pruritus	57.8% 26/45 • Throughout study period, up to 24 weeks
General disorders Injection site haemorrhage	17.8% 8/45 • Throughout study period, up to 24 weeks
Gastrointestinal disorders Pain oral cavity/throat	42.2% 19/45 • Throughout study period, up to 24 weeks
Nervous system disorders Dysgeusia	17.8% 8/45 • Throughout study period, up to 24 weeks
Gastrointestinal disorders Stomatitis/mouth ulcers	20.0% 9/45 • Throughout study period, up to 24 weeks
Gastrointestinal disorders Abdominal pain	11.1% 5/45 • Throughout study period, up to 24 weeks
Metabolism and nutrition disorders Anorexia	17.8% 8/45 • Throughout study period, up to 24 weeks
Gastrointestinal disorders Diarrhoea	40.0% 18/45 • Throughout study period, up to 24 weeks
Gastrointestinal disorders Nausea	35.6% 16/45 • Throughout study period, up to 24 weeks
Gastrointestinal disorders Vomoting	22.2% 10/45 • Throughout study period, up to 24 weeks
General disorders Fatigue	17.8% 8/45 • Throughout study period, up to 24 weeks
Skin and subcutaneous tissue disorders Acne	24.4% 11/45 • Throughout study period, up to 24 weeks
Skin and subcutaneous tissue disorders Alopecia	24.4% 11/45 • Throughout study period, up to 24 weeks

Additional Information

Pharmaceuticals Group

Nippon Kayaku Co., Ltd.

Phone: +81-3-6731-5200

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place