Clinical study comparing the new immunosuppresive drug gusperimus with the conventional treatment in Wegener’s Granulomatosis

• Register: EUCTR
• Last refreshed on: 17 August 2015
• Main ID: EUCTR2011-001219-30-CZ
• Date of registration: 20/06/2011
• Prospective Registration: Yes
• Primary sponsor: Nordic Pharma France
• Public title: Clinical study comparing the new immunosuppresive drug gusperimus with the conventional treatment in Wegener’s Granulomatosis
• Scientific 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)
• Date of first enrolment: 18/08/2011
• Target sample size: 216
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-001219-30
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: no Parallel group: yes Cross over: no Other: yes Other trial design description: evaluator blind If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Czech Republic, France, Germany, Italy, Netherlands, Russian Federation, Slovakia, Spain, Sweden, United Kingdom, United States

Contacts

• Name: clinical department
• Affiliation: Prague Clinical Services, s.r.o.

• Name: clinical department
• Affiliation: Prague Clinical Services, s.r.o.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Documented diagnosis of WG according to the ACR classification criteria.
2. Diagnosis of WG at least 6 months before entry and initial induction therapy with a combination of GC and an immunosuppressive (CYC or MTX) or rituximab.
3. Relapse of WG with or without ongoing GC, and/or immunosuppressive therapy with AZA/MMF/MTX or LEF. The minimum disease activity is defined by the presence of one new/worse major or three new/worse minor BVAS (version 3) items.
4. Patients between 18 – 75 years.
5. Medically acceptable and reliable contraception method during the study course.
(Women should not become pregnant for at least 6 months after CYC treatment).
6. Written informed consent for study participation given by the patient.
7. Patients able and prepared to self-administer the study medication or having a relative/third person able to do it.
8. Ability to read, understand and record information required by protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion criteria:
1. Other multi-system autoimmune disorders, including systemic lupus erythematosus and anti-GBM disease.
2. Systemic vasculitis due to a viral infection.
3. CYC therapy intolerance, hypersensitivity or contraindication to CYC (active substance or any of the excipients) in patients with severe relapse of WG.
4. Hypersensitivity or contraindication to
- Spanidin (active substance or any of the excipients) or
- both MTX (active substance or any of the excipients) and AZA (active
substance or any of the excipients) or
- methylprednisolone, prednisolone or other corticosteroids (active substance or any of the excipients).
5. Underlying medical conditions, which in the opinion of the Investigator place the patient at an unacceptable risk level for participating in a study.
6. Previous randomisation in this study.
7. CYC, 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.
8. Previous treatment with gusperimus.
9. Participation in another clinical trial with investigational drugs within the last 3 months before screening or during the present trial period.
10. Pregnant or breast-feeding females.
11. Active bacterial/viral infection (HIV, Hepatitis B, Hepatitis C, Tuberculosis).
12. Patients with eGFR < 15 mL/min/1.73m2 (MDRD equation).
13. ALT, AST, bilirubin, and ALP levels above 2 x the upper normal limit.
14. Inadequate bone-marrow function: WBC < 4000/mm3, haemoglobin < 8 g/dL, neutrophils < 2500/mm3, platelets < 100 000/mm3.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Relapse of Wegener’s Granulomatosis
MedDRA version: 13.1 Level: PT Classification code 10047888 Term: Wegener's granulomatosis System Organ Class: 10047065 - Vascular disorders
MedDRA version: 13.1 Level: LLT Classification code 10047889 Term: Wegeners granulomatosis System Organ Class: 10047065 - Vascular disorders

Intervention(s)

Product Name: Gusperimus
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: gusperimus
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Trade Name: Endoxan® 500 mg
Product Name: Cyclophosphamidum 500 mg
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: cyclophosphamide
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-

Trade Name: Azathioprin-ratiopharm® 25 mg Filmtabletten
Product Name: Azathioprine 25 mg
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: azathioprine
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Trade Name: Metex 2,5 mg Tabletten
Product Name: Methotrexate 2.5 mg
Pharmaceutical Form: Tablet
INN or Proposed INN: methotrexate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-

Trade Name: METOJECT 10 mg/ml, solution injectable en seringue pré-remplie
Product Name: Methotrexate 25 mg
Pharmaceutical Form: Solution for injection
INN or Proposed INN: methotrexate
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

Main Objective: The aim of the study is to assess the efficacy (superiority testing) of gusperimus compared to conventional treatment in patients with a relapse of WG with or without ongoing steroids, and/or immunosuppressive therapy (AZA/MMF/MTX or LEF).

Timepoint(s) of evaluation of this end point: Achievement of BVAS = 2 within 24 weeks
Maintenance of BVAS = 2 until the end of 52nd week

Primary end point(s): The primary efficacy variable is the rate of patients showing, within 24 weeks of trial entry, response with the level of disease activity BVAS = 2 that is maintained without relapse until the end of the trial (Week 52).

Secondary Objective: To evaluate the safety and quality of life of gusperimus treatment compared to standard treatment in patients with relapse of WG receiving GC

The pharmacokinetic parameters
- to examine the pharmacokinetics of s.c. gusperimus in this patient population
- to assess inter- and intra- subject variability in gusperimus pharmacokinetics following chronic s.c. administration.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: please see E.5.2

Secondary end point(s): - 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).
- 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).
- Frequency of severe relapses (defined as at least one major BVAS item).
- Frequency of non-severe relapses (defined as at least 3 minor BVAS items with no major BVAS items).
- VDI score change from baseline to month 12.
- 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).
- 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).
- 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).
- Pharmacokinetic parameters AUC, Cmax, Tmax and T½ calculated from the measured plasma samples collected at regular time intervals after administration of gusperimus on the first day of three treatment cycles.
- Pooled physical and mental SF 36 domains change from baseline to month 6.
- Pooled physical and mental SF 36 domains change from baseline to month 12.
- The total corticosteroid exposure.
- Change in EQ5D between baseline and month 12.

Secondary ID(s)

NO005-NK103

2011-001219-30-DE

Source(s) of Monetary Support

Nordic Pharma France