Submitted by: RAYMOND VAL PADUA 2019-05-03 03:53:35 Last Updated by: Principe, Jeverly Ann S 2019-05-27 11:05:42 Export to PDF

An exploratory maintenance trial of BI 655064 in patients with lupus nephritis




An exploratory maintenance trial evaluating the effect of BI 655064 in Lupus Nephritis patients who have achieved a meaningful response either at the end of 1293.10 or after an induction treatment outside of 1293.10

This is a phase II, randomised, double-blind, parallel-design, dose-ranging, placebocontrolled, exploratory maintenance trial. The trial is designed to evaluate the long term efficacy and safety of different doses of BI 655064 in patients with LN; and to study the effect of steroid tapering and steroid withdrawal during 52 weeks of maintenance treatment.

Start Date Duration in Months Target Completion Date Actual Completion Date
2019-06-28 52 2023-10-28 2020-06-28


Not stated

Institution Classification Region LTO #
Boehringer Ingelheim (Philippines), Inc. Private Business NCR LTO-3000001365916
Institution Amount Region
Boehringer Ingelheim Singapore, Pte. Ltd. N/A Singapore
Name E-Mail Phone Number Postal Address
Dr. Greta Cortez +63 2 867 0943 Boehringer Ingelheim Phil., 23rd Floor Citibank Tower, 8741 Paseo de Roxas, Makati City
Name E-Mail Phone Number Postal Address
Dr. Greta Cortez +63 2 867 0943 Boehringer Ingelheim Phil., 23rd Floor Citibank Tower, 8741 Paseo de Roxas, Makati City
Name Expertise Affiliation
Harold Michael P. Gomez, MD Rheumatology Angeles University Foundation Medical Center
Rhona Laylo Recto, MD Rheumatology Mary Mediatrix Medical Center
Edgar Ramiterre, MD Rheumatology Southern Philippines Medical Center
James Bermas, MD Rheumatology Chong Hua Hospital
Merle Y. Barba, MD Rheumatology Cebu Doctors' University Hospital
Project Location Institutional Ethics Review Board
Angeles University Foundation Medical Center Angeles University Foundation Medical Center Institutional Ethics Review Committee
Mary Mediatrix Medical Center Mary Mediatrix Medical Center Institutional Ethics Review Board
Southern Philippines Medical Center SPMC Hospital Research Committee
Chong Hua Hospital Chong Hua Hospital Ethics Review Committee
Cebu Doctors' University Hospital Cebu Doctors' University Hospital - Institutional Ethics Review Committee

Lupus Nephritis

Primary endpoint:

- Proportion of patients with CRR and without any renal flares at week 52.

 Secondary endpoints:

- Proportion of patients with proteinuria <0.8g/d and without any renal flares at week 52.
- Proportion of patients with CRR at week 52 and sustained steroid reduction to ≤5 mg/d from week 26 to week 52.
- Proportion of patients experiencing at least one renal flare during 52 weeks.
- Time to first renal flare over the course of 52 weeks.
- Change from baseline in SLEDAI at weeks 12, 26, 42 and 52.


  • Canada
  • France
  • Germany
  • Italy
  • Japan
  • Malaysia
  • Mexico
  • Philippines
  • South Korea
  • Thailand

Clinical Trial




Inclusion criteria
1. Male or female patients.
- Women of childbearing potential* 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/AZA and for at least 90 days after cessation of MMF/AZA.
* 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.


2. 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.


Exclusion criteria
1.  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.

2.  Significant central nervous system symptoms related to SLE based on investigators assessment.

3. Clinically important acute or chronic infections including but not limited to HIV, hepatitis B or C.

4. Impaired hepatic function defined as serum AST/ALT, bilirubin or alkaline phosphatase> 2 x ULN.

5. Estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73m2 at screening (using CKD-EPI formula).

6. Known hypersensitivity to any constituents of the trial medication; and/or contraindications to MMF or AZA or glucocorticoids.

7. The use of any restricted medications (see section or any drug considered likely to interfere with the safe conduct of the trial.

8. Unable to comply with the protocol in the investigator’s opinion.

9. 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.

10.  Women who are pregnant, nursing, or who plan to become pregnant while in the trial.

For Group 2 patients only:
1. Clinically significant current non-SLE related renal diseases based on investigator’s judgment (e.g. post–infectious glomerulonephritis, pyelonephritis, interstitial nephritis,

2. Dialysis within 12 months of screening.

3. Live vaccination within 6 weeks prior to randomisation.

4. Antiphospholipid syndrome defined as positive antiphospholipid antibodies and either history of any thrombotic event or history of miscarriage.

5. 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.

6. 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
- Treatment with any biologic B-cell depleting therapy (e.g. anti-CD20) within 6 months prior to randomisation.

7. 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.

8. 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.

9. Previous enrolment in 1293.10 and did not complete the trial.





Double Blind

Group 1 patients will continue to receive the same treatment allocation as previously assigned in the 1293.10 trial (i.e., either 120mg or 180mg or 240mg or Placebo) at Visit 1. If initiated and depending on the results from 1293.10 interim analysis, group 2 patients will be randomised at Visit 2 to receive one of the following possible treatment allocations:- If two best BI 655064 doses are chosen for comparison with placebo, patients will be randomised in a ratio of 1:1:1 (30 patients per treatment arm) or- If one best BI 655064 dose is chosen for comparison with placebo, patients will be randomised in the ratio of 1:1 (30 patients per treatment arm) The assignment will occur in a blinded fashion via Interactive Response Technology (IRT). Details regarding the use of IRT are described in the site IRT user manual available in the ISF.


Patients with LN class III-V are at high risk for irreversible kidney damage leading to ESRD, dialysis and death. Although not yet approved in most countries for the treatment of LN, the combination of either CYC or MMF with glucocorticoids is considered as current standard of care (SOC) for induction therapy in LN. The current SOC for maintenance therapy is a combination of low dose MMF or azathioprine (AZA) with low dose glucocorticoids. However, only 20-30% of LN patients treated with induction therapy achieved a complete renal response (CRR) within 1 year and another 20-30% with a partial renal response (PRR). Patients with a CRR, or PRR with proteinuria there is a relevant risk of relapsing which justifies long-term maintenance therapy (R15-3724).

Furthermore, a large number of patients who achieved a renal response by induction therapy still require treatment with steroids at doses >5 mg/d. The European Medicines Agency (EMA) guideline recommends at least one year maintenance  treatment after completion of induction therapy for LN (R15-3716). As a result, steroid-related side effects are frequently observed in LN patients, therefore reducing steroid dosage is a critical target in maintenance therapy for LN (P15-01916). In addition, both immunosuppressants used for maintenance therapy of LN have associated side-effects, s.a. gastrointestinal related side effects and leucocytopenia for both MMF and AZA; amenorrhoea for MMF and liver damage for AZA. Thus, alternative immunosuppressant with a better safety and efficacy profile for LN maintenance therapy with the aim to reduce steroid doses should be explored. Blocking the CD40-CD40L pathways will impact multiple mechanisms which involved in
pathology of LN by inhibiting B-cell and T-cell responses as well as directly influence the inflammation in the kidney by decreasing CD40L induced MCP1 secretion of endothelial
cells, mesangial cells and CD40L induced IL-6 secretion by proximal tubular epithelial cells.

Therefore, targeting the CD40-CD40L pathway is considered a potential effective approach for the treatment of this disease. The therapeutic benefit or specific adverse events in patients cannot always be anticipated during the trial setup. Later on there may be new scientific knowledge about biomarkers and other factors contributing to diseases or the action of a drug. In order to be able to address future scientific questions, patients will be asked to voluntarily donate biospecimens for
banking. If the patient agrees, banked samples may be used for future drug development projects, e.g. to identify patients that are more likely to benefit from a treatment or experience an adverse event, and thereby better match patients with therapies.

Phase II




28 Jun 2019

Utilization Utilization Info

The Boehringer Ingelheim transparency and publication policy can be found on the following
web page: The rights of the investigator and of the sponsor
with regard to publication of the results of this trial are described in the investigator contract.
As a rule, no trial results should be published prior to finalisation of the Clinical Trial Report.

Oral Presentation
Drug Literature

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