| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
| inflammation of the kidneys |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10025140 |
| E.1.2 | Term | Lupus nephritis |
| E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
|
| 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 |
The main objectives of this trial are to evaluate the long term efficacy and safety of different
doses of BI 655064 versus placebo as add-on therapy to SOC during maintenance therapy for
lupus nephritis. |
|
| E.2.2 | Secondary objectives of the trial |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
- Male or female patients.
- Women of childbearing potential* and men able to father a child must be ready and able
to use two reliable methods of birth control simultaneously, one of which must be highly
effective. Highly effective birth control per ICH M3(R2) is a method that result in a low
failure rate of less than 1% per year when used consistently and correctly. The reliable
methods of birth control must be used before starting MMF/AZA and the trial drug; then continue during the trial period; and for at least 50 days after the last dose of MMF and trial medication. In case a female patient is treated with AZA the contraception shall continue for 90 days after treatment with AZA. A list of contraception methods meeting these criteria is provided in
the patient information.
- Sexually active men must be ready to use condoms ** during treatment with MMF and
for at least 90 days after cessation of MMF.
* A woman is considered of childbearing potential, i.e. fertile, following menarche and until becoming
postmenopausal unless permanently sterile.
- Permanent sterilisation methods include hysterectomy, bilateral oophorectomy and bilateral
salpingectomy.
- Tubal ligation is NOT a method of permanent sterilisation.
- A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.
** Condoms are applied for both reproductively competent and vasectomised men, because the risks
associated with the transfer of seminal fluid also apply to men who have had a vasectomy. In addition,
female partners of male patients treated with MMF are recommended to use highly effective
contraception during treatment and for a total of 90 days after the last dose of MMF.
- Signed and dated written informed consent in accordance with ICH-GCP and local
legislation prior to admission to the trial.
For Group 1 patients only:
- Achieved either a CRR or a PRR or proteinuria ≤ 1g/d (or UP/UC ≤ 1) at the end of
1293.10.
For Group 2 patients only:
- Age 18 –70 years at screening. For patients in Japan, age 20 – 70 years at screening.
- Diagnosis of SLE by American College of Rheumatology (ACR) criteria 1997 with at
least 4 criteria documented, one of which must either be a positive ANA or a positive
anti-dsDNA antibody at the time of starting induction therapy (historical data).
- Lupus Nephritis Class III or IV (co-existing class V permitted) based on ISN/RPS 2003
classification with either active or active/chronic disease, proven by renal biopsy before
the start of induction therapy (historical data).
- Achieved either a CRR or a PRR or proteinuria ≤ 1.5g/d (or UP/UC ≤ 1.5) after at least 6
months of induction treatment (either with SOC (CYC or MMF-based) or SOC in
combination with other available therapies used for induction treatment of LN e.g.
tacrolimus, cyclosporin, experimental drug etc.); and within 12 months after initiating
induction therapy outside of 1293.10 trial.
- Steroid dose ≤ 15 mg/d prednisone-equivalent at baseline.
|
|
| E.4 | Principal exclusion criteria |
Evidence of current or previous clinically significant diseases or medical conditions
other than lupus, or findings of the medical examination (including vital signs and ECG)
that, in the opinion of the investigator, would compromise the safety of the patient or the
quality of the data. This criterion provides an opportunity for the investigator to exclude
patients based on clinical judgment, even if other eligibility criteria are satisfied.
- Significant central nervous system symptoms related to SLE based on investigators
assessment.
- Clinically important acute or chronic infections including but not limited to HIV,
hepatitis B or C.
- Impaired hepatic function defined as serum AST/ALT, bilirubin or alkaline phosphatase
> 2 x ULN.
- Estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73m2 at screening (using
CKD-EPI formula).
- Known hypersensitivity to any constituents of the trial medication; and/or
contraindications to MMF or AZA or glucocorticoids.
- The use of any restricted medications (see section 4.2.3.1) or any drug considered likely
to interfere with the safe conduct of the trial.
- Unable to comply with the protocol in the investigator’s opinion.
- Chronic alcohol or drug abuse or any condition that, in the investigator’s opinion, makes
them an unreliable trial patient or unlikely to complete the trial.
- Women who are pregnant, nursing, or who plan to become pregnant while in the trial.
For Group 2 patients only:
- Clinically significant current non-SLE related renal diseases based on investigator’s
judgment (e.g. post–infectious glomerulonephritis, pyelonephritis, interstitial nephritis,
glomerulosclerosis).
- Dialysis within 12 months of screening.
- Live vaccination within 6 weeks prior to randomisation.
- Antiphospholipid syndrome defined as positive antiphospholipid antibodies and either
history of any thrombotic event or history of miscarriage.
- Diabetes mellitus if poorly controlled or accompanied by known diabetic retinopathy or
diabetic nephropathy. It is in the investigator’s judgment if the diabetes is sufficiently controlled for the patient to enter the trial.
- With regard to previous induction treatments, the following applies:
- Treatment with tacrolimus or cyclosporine or mizoribine within 1 month prior to
randomisation.
- Treatment with belimumab or other “BLyS antagonists” or another investigational
drug within 3 months or 5 half-lives, whichever is greater, prior to randomisation.
- Treatment with abatacept or cyclophosphamide within 3 months prior to
randomisation.
- Treatment with any biologic B-cell depleting therapy (e.g. anti-CD20) within 6
months prior to randomisation.
- Are not eligible according to the following tuberculosis (TB) screening criteria:
- Have signs or symptoms suggestive of current active or latent TB upon medical
history, physical examination and/or a chest radiograph (both posterior-anterior and
lateral views, taken within 3 months prior to the first administration of study drug and
read by a qualified radiologist).
-- Have history of latent or active TB prior to screening, except for patients who have
documentation of having completed an adequate treatment regimen according to local
guidelines within the past 3 years and at least 6 months prior to the first
administration of study drug.
-- Have positive QuantiFERON-TB Gold In-Tube test within 2 months prior to or
during screening, in which latent or active TB has not been ruled out, except for
patients with history of TB and documentation of having completed an adequate
treatment regimen at least 6 months prior to the first administration of study drug.
- Any documented active or suspected malignancy or history of malignancy within 5 years
prior to screening, except appropriately treated basal cell carcinoma of the skin or in situ
carcinoma of uterine cervix.
- Previous enrolment in 1293.10 and did not complete the trial. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| 1) proportion of patients with complete renal reponse (CRR) and without any renal flares |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
1) Proportion of patients with proteinuria <0.8g/d and without any renal flares at week 52.
2) Proportion of patients with CRR at week 52 and sustained steroid reduction to ≤5 mg/d from week 26 to week 52.
3) Proportion of patients experiencing at least one renal flare during 52 weeks.
4) Time to first renal flare over the course of 52 weeks.
5) Change from baseline in SLEDAI at weeks 12, 26, 42 and 52. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) week 52
2) week 52
3) week 52
4) week 52
5) weeks 12, 26, 42 and 52 |
|
| 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 | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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.8.2.4 | Number of treatment arms in the trial | 4 |
| 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 | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 15 |
| 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 | No |
| 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 |
| Australia |
| Austria |
| Canada |
| Czech Republic |
| France |
| Germany |
| Greece |
| Hong Kong |
| Italy |
| Japan |
| Korea, Republic of |
| Malaysia |
| Mexico |
| Philippines |
| Poland |
| Portugal |
| Serbia |
| Spain |
| Thailand |
| Turkey |
| United Kingdom |
| United States |
|
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| 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 | 4 |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
| E.8.9.2 | In all countries concerned by the trial days | 7 |
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