A Randomised, Double-Blind, Placebo Controlled, Parallel-Group, Multicenter Study To Evaluate The Efficacy and Safety of Two Doses of Ocrelizumab in Subjects With WHO or ISN Class III or IV Nephritis Due To Systemic Lupus Erythematosus - BELONG
- Conditions
- upus Nephritis
- Registration Number
- EUCTR2006-005357-29-DE
- Lead Sponsor
- F. Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 369
Patients must meet the following criteria to be eligible for study entry. Documentation of each specific criterion must be present in the patient’s chart notes:
1. Age 16 years or above at the time of the screening, unless the inclusion of minors is prohibited by the local regulations.
2. Ability and willingness to provide written informed consent (or to obtain consent from a parent guardian where applicable) and to comply with the schedule of protocol requirements.
3. Diagnosis of SLE according to ACR criteria. At least 4 criteria must have been present for the diagnosis of SLE. The 4 criteria do not have to be present at the time of screening.
4. Active lupus nephritis defined as follows: Biopsy proven (within 6 months prior to randomization) WHO or ISN Class III or IV LN (excluding III (C), IV-S (C) and IV-G (C),
Patients are permitted to have co-existing Class V (see Table 1). Whenever possible, biopsies should be graded and reported following ISN/RPS classification scheme. AND The presence of: Urinary protein to Urinary creatinine ratio = 1. The proteinuria must not have improved by = 50% in the preceding 6 months. The urine sample used to define this ratio is the 24 hour screening sample which is measured by the central laboratory. If collection and analysis of a 24 hour urine sample is not possible prior to randomization then a timed urine collection (at least 12 hours) should be obtained.
Determination of eligibility based on a first-void morning 'spot' urine sample is acceptable if collection and analysis of a timed urine sample is not possible prior to randomization.
5. For patients of reproductive potential (males and females), a reliable means of contraception must be used for the duration of the study (e.g. hormonal contraceptive, intrauterine device, physical barrier) according to local guidelines and the treating physician’s recommendations. The relevant section of the product label for CYC, MMF or AZA (as appropriate) should be followed.
6. Female patients of childbearing potential must have a negative serum pregnancy test from the screening visit prior to enrollment at Day 1.
Are the trial subjects under 18? yes
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
1. Currently active retinitis, poorly controlled seizure disorder,
acute confusional state, myelitis, stroke or stroke syndrome,
cerebellar ataxia or dementia.
2. Severe renal impairment as defined by calculated (Cockcroft-Gault) GFR < 25 mL/min, or the presence of oliguria or renal biopsy results indicating chronic
irreversible renal scarring.
3. Lack of peripheral venous access.
4. Pregnancy or breast feeding mothers.
5. History of severe allergic or anaphylactic reactions to humanized, chimeric or murine monoclonal antibodies or i.v. immunoglobulin.
6. Known severe chronic pulmonary disease.
7. Evidence of significant uncontrolled concomitant diseases in
any organ system not related to SLE (e.g. renal thrombosis,
atherosclerotic cardiovascular disease, diabetes mellitus,
accelerated hypertension, poorly controlled COPD or asthma
etc), which, in the investigator’s opinion, would preclude
patient participation.
8. Concomitant condition (e.g. asthma, Crohn’s disease, etc)
which has required treatment with systemic corticosteroid
(excluding topical or inhaled steroids) at any time in the
52 weeks prior to screening.
9. Known HIV or chronic active Hepatitis B or chronic active
Hepatitis C infection.
10. Known active, clinically significant infection of any kind (with the exception of fungal infection of nail beds or oral thrush) or any major
episode of infection requiring hospitalization or treatment
with intravenous anti-infectives in the 14 days prior to Day 1. Patients may be enrolled in the presence of recent minor infections not requiring treatment with anti-infectives (e.g. viral upper respiratory tract infection, viral gastroenteritis), if in the investigator´s opinion, the infection has resolved prior to Day 1 and is unlikely to persent additional risk to the subject.
11. History of serious recurrent or chronic infection. A chest
radiograph will be performed during screening, if not
performed in the 12 weeks prior to screening, to assess
infection. If there is any evidence of pulmonary infection a
chest radiograph should be performed.
12. History of cancer, including solid tumors, hematological
malignancies and carcinoma in situ (except basal cell
carcinoma, squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that has been excised and cured).
13. History of alcohol or drug abuse in the 52 weeks prior to
screening.
14. Major surgery in the 4 weeks prior to screening, excluding
diagnostic surgery.
15. Previous treatment with CAMPATH-1H.
16. Previous treatment with a BAFF directed treatment
(e.g. anti-BLyS) in the 12 months prior to screening.
17. Previous treatment with a B-cell targeted therapy (e.g. anti-CD20, anti-CD22) other than one directed at BAFF.
18. Treatment with any investigational agent in the 28 days prior
to screening or within five half-lives of the investigational
drug (whichever is longer).
19. Receipt of any live vaccines in the 6 weeks prior to Day 1.
20. Intolerance or contraindication to oral or i.v. corticosteroids.
21. Treatment with more than 1 g CYC (cumulative dose) in the
6 months prior to screening period.
22. Receipt of more than 3 g i.v. pulse methylprednisolone (cumulative
dose) within the 12 weeks prior to screening.
23. Receipt of prednisone doses > 20 mg/day ( or equivalent including parenteral corticosteroids, except for pulse steroids as defined in exclusion criteria #22) for longer than 14 days within a 12 weeks period prior to screening. During the 14 days prior to scr
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To investigate the ability of the ocrelizumab regimen in<br>combination with standard of care treatment (SOC) to induce a<br>complete or partial renal response, as assessed by renal function,<br>urinary sediment and proteinuria in patients with ISN/RPS or<br>WHO class III or IV lupus nephritis.;Secondary Objective: • To assess the safety and tolerability of ocrelizumab.<br>• To evaluate the PK, immunogenicity and PD parameters of ocrelizumab in this patient population.<br>• To evaluate corticosteroid sparing in patients receiving ocrelizumab.<br>• To evaluate the effect of ocrelizumab on extra-renal disease manifestations<br>• To evaluate the impact of ocrelizumab on symptoms and patient functioning using the SF-36, Facit Fatigue and modified Brief Pain Inventory (mBPI-SF).;Primary end point(s): The comparison of the two experimental arms (ocrelizumab 400 mg versus ocrelizumab 1000 mg) will be explored within this study).<br><br>
- Secondary Outcome Measures
Name Time Method