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

• Register: EUCTR
• Last refreshed on: 19 April 2022
• Main ID: EUCTR2006-005357-29-NL
• Date of registration: 22/11/2007
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd
• Public title: 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
• Scientific title: 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
• Date of first enrolment: 22/02/2008
• Target sample size: 369
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-005357-29
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Bulgaria, France, Germany, Hungary, Netherlands, Poland, Portugal, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
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

Exclusion criteria:
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 present 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 criterion #22) for longer
than 14 days within a 12 weeks period prior to screening.
During the 14 days prior to screen

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

Health Condition(s) or Problem(s) studied

Lupus Nephritis

Intervention(s)

Product Name: ocrelizumab
Product Code: RO 496-4913
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: ocrelizumab
Current Sponsor code: RO 496-4913
Other descriptive name: RhuMAb 2H7
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 30-
Pharmaceutical form of the placebo: Concentrate for solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Primary end point(s): The primary efficacy endpoint of this study is the proportion of patients with a clinical response in the following three mutually exclusive categories at Week 48:
1. Patients who achieve a Complete Renal Response (CRR)
2. Patients who achieve a Partial Renal Response (PRR)
3. Patients who do not achieve a Renal Response (neither a CRR nor a PRR) will be classed as non-responders [NR] at Week 48.

Secondary Objective: • To assess the safety and tolerability of ocrelizumab.
• To evaluate the PK, immunogenicity and PD parameters of ocrelizumab in this patient population.
• To evaluate corticosteroid sparing in patients receiving ocrelizumab.
• To evaluate the effect of ocrelizumab on extra-renal disease manifestations
• To evaluate the impact of ocrelizumab on symptoms and patient functioning using the SF-36, Facit Fatigue and modified Brief Pain Inventory (mBPI-SF).

Main Objective: To investigate the ability of the ocrelizumab regimen in
combination with standard of care treatment (SOC) to induce a
complete or partial renal response, as assessed by renal function,
urinary sediment and proteinuria in patients with ISN/RPS or
WHO class III or IV lupus nephritis.

Secondary ID(s)

2006-005357-29-GB

WA20500

Ethics review

Status: Approved
Approval date: 22/02/2008
Contact:

Results

• Results available: Yes
• Date Posted: 07/08/2015
• Date Completed: 28/10/2013
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2006-005357-29/results