| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
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. |
|
| E.2.2 | Secondary objectives of the trial |
• 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). |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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.
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. Whenever possible, biopsies should be graded and reported following ISN/RPS classification scheme. AND Presence of: Urinary protein to Urinary creatinine ratio (Upr:Ucr) > 1 (which must not have improved by ≥ 50% in the preceding 6 months).
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. |
|
| E.4 | Principal exclusion criteria |
Exclusions Related to SLE
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 (by
Cockcroft-Gault) GFR < 25 mL/min, or the presence of
oliguria (defined as a documented urine volume
< 400 mL/24hr) or renal biopsy results indicating chronic
irreversible renal scarring (either > 50% of glomeruli with
sclerosis or > 50% interstitial fibrosis on renal biopsy).
Exclusions Related to General Health
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 (FEV1 < 50%
predicted or functional dyspnea ≥ Grade 3 on the MRC
Dyspnea Scale).
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 infection of any kind (but excluding fungal
infection of nail beds or oral thrush which has resolved before
Day 1) within 30 days prior to Day 1. In addition, any major
episode of infection requiring hospitalization or treatment
with intravenous anti-infectives in the 30 days prior to Day 1
or oral anti-infectives in the 14 days prior to Day 1.
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 of the skin 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.
Exclusions Related to Medications
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 other than
one directed at BAFF (e.g. anti-CD20, anti-CD22).
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 (it
is recommended that a patient’s vaccination record and the
need for immunization prior to receiving ocrelizumab should
be carefully investigated).
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 2 g i.v. methylprednisolone (cumulative
dose) within the 28 days prior to screening.
23. Receipt of oral prednisone doses > 20 mg/day for longer than
the 14 days prior to screening. During the 14 days prior to
screening patients may be treated with high-dose oral
prednisone (up to 1 mg/kg).
24. Treatment with a calcineurin inhibitor (e.g. cyclosporin,
tacrolimus) within the 12 weeks prior to screening.
Exclusions Related to Laboratory Findings
25. Aspartate aminotransferase or alanine aminotransferase or
amylase > 2.5 times the upper limit of normal, unless caused
by SLE. Patients with elevated serum amylase may be eligible
if serum lipase is within normal limits and clinical signs of
pancreatitis are not present.
26. Neutrophils < 1.5 × (10x10x10)/μL. If the absolute neutrophil count is < 1.5 × 1(10x10x10)/μL but the investigator has assessed the neutropenia is due to SLE, the
patient may be eligible for the study. This determination will
be made after discussion with the Medical Monitor.
27. Hemoglobin < 7 g/dl.
28. Platelet count < 50 000/μL.
If the platelet count is < 50,000/μL but > 10,000/μL and the
investigator believes this is due to SLE, the patient may be
eligible for the study. This determination will be made after
discussion with the Medical Monitor.
29. Positive serum hCG measured prior to the first ocrelizumab
infusion.
30. Positive hepatitis BsAg or hepatitis C serology. Patients who
are HBsAg negative but HBcAb positive may be enrolled with
a negative DNA test. |
|
| E.5 End points |
| E.5.1 | 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.
|
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 68 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| Please refer to setion 3.1.6 "End of Study" of the Protocol |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
Print
