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Submitted by: Kristal Ann Placido 2017-08-07 00:00:00 Last Updated by: Kristal Ann Placido 2020-03-02 10:56:50


A Randomized, Controlled Double-blind Study Comparing the Efficacy and Safety of Orelvo (voclosporin) (23.7 mg Twice Daily) with Placebo in Achieving Renal Response in Subjects with Active Lupus Nephritis

PHRR170812-001648

DTN 20170306160902

Unspecified

A Randomized, Controlled Double-blind Study Comparing the Efficacy and Safety of Orelvo (voclosporin) (23.7 mg Twice Daily) with Placebo in Achieving Renal Response in Subjects with Active Lupus Nephritis

This is a Phase 3, multicenter, randomized, prospective, double-blind, parallel-group, placebo-controlled, 2-arm comparison study of Orelvo versus matching placebo. Subjects who have provided a signed and dated informed consent will be screened into the study up to 30 days before randomization. During the screening period, eligibility criteria will be assessed. A kidney biopsy may be performed, provided the subject has given consent and provided the results can be obtained and reviewed before baseline. Subjects who meet all of the inclusion criteria and none of the exclusion criteria will be eligible for randomization into the study.
Baseline assessments will be performed before the first dose of study treatment is administered on Day 1. The baseline assessments of the serum creatinine and urine protein laboratory parameters will be established by using the mean of the 2 pre-randomization values. Using an interactive web response system (IWRS), eligible subjects will be randomized to receive either oral Orelvo 23.7 mg BID or matching placebo for 52 weeks. All subjects should receive 0.5 g/day IV methylprednisolone on Days 1 and 2 before changing to a reducing course of oral corticosteroid therapy on Day 3. Starting at the Baseline Visit, all subjects will also receive background therapy with MMF.
All subjects will return for assessment of efficacy and safety at Day 2 and Weeks 2, 4, 8, 12, 16, 20, 24, 30, 36, 42, 48, and 52. In addition, subjects not on MMF during screening, will start receiving MMF at the Baseline Visit and will return for local complete blood count assessments at Weeks 1 and 3 after randomization.
All subjects, completed or withdrawn, will complete the End of Treatment/Early Termination assessments (Visit 15) at Week 52 or at the time of early termination. Subjects who do not enroll in the continuation study will attend the Safety Follow-up Visit (Visit 16) at Week 56 to collect any new AEs and concomitant medications. At the follow-up visit, UPCR and eGFR will be assessed as well. 

Regime Classification Priority
2010 - 2016 Health Service Delivery
Start Date Duration in Months Target Completion Date Actual Completion Date
2017-09-08 20 2019-05-08 0000-00-00

Completed

Institution Classification Region LTO #
Aurinia Pharmaceuticals Inc. Private Business Canada CDRR-NCR-CRO-25
Institution Classification Region LTO #
CMIC Asia-Pacific (Philippines), Inc. Private Business NCR CDRR-NCR-CRO-25
Institution Region
Aurinia Pharmaceuticals Inc. Canada
Name E-Mail Institution and Institution Address
Kristal Ann M. Placido kristalann-placido@cmicgroup.com Blk 1 Lot 5 Cerritos Terraces Daang Hari Bacoor Cavite 1402 Philippines
Name E-Mail Institution and Institution Address
Dr. Eteri Tsetskhladze Eteri.Tsetskhladze@wwctrials.com 5, Chavchavadze Avenue, Tbilisi, Georgia, 0179
Name Expertise Affiliation
Allan E. Lanzon, MD Rheumatologist Mary Mediatrix Medical Center
Bernadette Heizel Manapat-Reyes, MD Rheumatologist Philippine General Hospital
Edgar Ramiterre, MD Rheumatologist Southern Philippines Medical Center
Eric Jason Amante, MD Rheumatologist Manila Doctors Hospital
Harold Michael P. Gomez, MD Rheumatologist Angeles University Foundation Medical Center
Juan Javier T. Lichauco, MD Rheumatologist St. Luke's Medical Center - Quezon City
Linda Charmaine D. Roberto, MD Rheumatologist Jose R. Reyes Memorial Medical Center
Llewellyn T. Hao, MD Rheumatologist Davao Doctors Hospital
Michael L. Tee, MD Rheumatologist Medical Center Manila
Sandra Navarra, MD Rheumatologist St. Luke's Medical Center - Quezon City
Project Location Institutional Ethics Review Board
Mary Mediatrix Medical Center Mary Mediatrix Medical Center Research Ethics Review Committee
Philippine General Hospital Philippine General Hospital Ethics Review Board
Southern Philippines Medical Center DOH XI Cluster Ethics Review Committee
Manila Doctors Hospital Manila Doctors Hospital Institutional Review Board
Angeles University Foundation Medical Center Angeles University Foundation Medical Center Institutional Ethics Review Committee
St. Luke's Medical Center - Quezon City St. Luke's Medical Center Institutional Ethics Review Board
Jose R. Reyes Memorial Medical Center Jose R. Reyes Memorial Medical Center Ethics Review Committee
Davao Doctors Hospital Davao Doctors Hospital Ethics Review Committee
Medical Center Manila Manila Medical Ethics Review Committee
St. Luke's Medical Center - Quezon City St. Luke's Medical Center Institutional Ethics Review Board

Active lupus nephritis

To assess the efficacy of Orelvo (voclosporin) compared with placebo in achieving renal response after 24 weeks of therapy in subjects with active lupus nephritis (LN)

To assess the safety, tolerability, and efficacy of Orelvo over 52 weeks compared with placebo in subjects with active LN

Recruiting

  • Argentina
  • Belarus
  • Brazil
  • Bulgaria
  • Canada
  • Chile
  • Colombia
  • Costa Rica
  • Croatia
  • Dominican Republic
  • Guatemala
  • Japan
  • Macedonia
  • Malaysia
  • Mexico
  • Netherlands
  • Peru
  • Philippines
  • Poland
  • Russia
  • Serbia and Montenegro
  • South Africa
  • South Korea
  • Spain
  • Taiwan
  • Thailand
  • Turkey
  • Ukraine
  • United States
  • Vietnam

Clinical Trial

DTN 20170306160902

DTN 20170306160902

2017-07-19

0000-00-00

30

Unspecified

Unspecified

08 Sep 2017

1. Written informed consent before any study-specific procedures are performed.
2. Male or female subjects with a minimum age of 18 (or legal age of consent if more than 18 years) to 75 years of age, inclusive, at the time of screening (Visit 1).
3. Previous diagnosis of systemic lupus erythematosus (SLE) according to the American College of Rheumatology criteria.
4. Subjects with evidence of active nephritis, defined as follows:
Kidney biopsy result within 2 years prior to screening indicating Class III, IV-S or IV-G (alone or in combination with Class V) LN with a doubling or greater increase of urine protein creatinine ratio (UPCR) within the last 6 months to a minimum of greater than or equal to 1.5 mg/mg at screening.
OR
Kidney biopsy result within 6 months prior to screening indicating Class III, IV-S or IV-G (alone or in combination with Class V) LN with a UPCR of greater than or equal to 1.5 mg/mg at screening.
OR
Kidney biopsy result within 6 months prior to screening indicating Class V LN and a UPCR of greater than or equal to  2 mg/mg at screening.
A biopsy can be performed during screening, if not available. The above criteria must be fulfilled at baseline.
5. In the opinion of the Investigator, subject requires high-dose corticosteroids and immunosuppressive therapy.
6. Subject is willing to take oral MMF for the duration of the study, either by continuing current MMF therapy or by initiating it on or before the Baseline Visit.
7. Women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline. Two effective forms of contraception must be used simultaneously unless abstinence is the chosen method. Subjects must use effective contraception during the study.
EXCLUSION:
1. Subjects unable or unwilling to give written informed consent and/or to comply with study procedures.
2. Estimated glomerular filtration rate (eGFR) as calculated by the Chronic Kidney Disease Epidemiology Collaboration equation of less than or equal to 45 mL/minute/1.73 m2 at screening confirmed before randomization.
3. Currently taking or known need for any of the medications listed in Prohibited Therapy and Concomitant Treatment at screening or during the study. This includes prohibited medications prior to screening.
4. Currently requiring renal dialysis (hemodialysis or peritoneal dialysis) or expected to require dialysis during the study period.
5. A previous kidney transplant or planned transplant within study treatment period.
6. Any known hypersensitivity or contraindication to MMF, mycophenolic acid, cyclosporine, corticosteroids or any components of these drug products.
7. Current or medical history of:
• Congenital or acquired immunodeficiency.
• In the opinion of the Investigator, clinically significant drug or alcohol abuse within 2 years prior to screening.
• Malignancy within 5 years of screening, with the exception of basal and squamous cell carcinomas treated by complete excision. Subjects with cervical dysplasia that is cervical intraepithelial neoplasia 1, but have been treated with conization or loop electrosurgical excision procedure and have had a normal repeat Papanicolaou test are allowed.
• Lymphoproliferative disease or previous total lymphoid irradiation.
• Severe viral infection (e.g., cytomegalovirus, hepatitis B virus, hepatitis C virus) within 3 months of screening; or known HIV infection. Severe viral infection is defined as active disease requiring antiviral therapy.
• Active tuberculosis (TB), or known history of TB/evidence of old TB if not taking prophylaxis with isoniazid.
8. Other known clinically significant active medical conditions, such as:
• Severe cardiovascular disease including congestive heart failure, history of cardiac dysrhythmia or congenital long QT syndrome. QT interval duration corrected for heart rate using method of Fridericia exceeding 480 msec in the presence of a normal QRS interval.
• Liver dysfunction (aspartate aminotransferase, alanine aminotransferase, or bilirubin greater than or equal to 2.5 times the upper limit of normal) at screening and, if abnormal at screening, then confirmed that the levels have returned to less than 2.5 times upper limit of normal before randomization.
• Chronic obstructive pulmonary disease or asthma requiring oral steroids.
• Bone marrow insufficiency unrelated to active SLE (according to Investigator judgment) with white blood cell count less than 2,500/mm3; absolute neutrophil count less than 1.3 × 10^3/microliter; thrombocytopenia (platelet count less than 50,000/mm3).
• Active bleeding disorders.
• Current infection requiring IV antibiotics.
9. Any overlapping autoimmune condition for which the condition or the treatment of the condition may affect the study assessments or outcomes (e.g., scleroderma with significant pulmonary hypertension; any condition for which additional immunosuppression is indicated). Overlapping conditions for which the condition or treatment is not expected to affect assessments or outcomes (e.g., Sjögren’s syndrome) are not excluded.
10. No vaccines using live organisms, virus or bacterial, are allowed during screening and while taking the study treatment.
11. Other major physical or psychiatric illness or major traumatic injury within 6 months prior to screening that may affect study conduct or interfere with study assessments or outcome.
12. Any other medical condition which, in the Investigator’s judgment, may be associated with increased risk to the subject or may interfere with study assessments or outcomes.
13. Subjects who are pregnant, breast feeding or, if of childbearing potential, not using adequate contraceptive precautions.
14. Participation in another interventional clinical study within 4 weeks prior to screening and/or receipt of investigational drugs within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to screening.
15. Subjects randomized and treated in a previous voclosporin clinical study.

Interventional

Orelvo (Voclosporin) and matching Placebo

Orelvo (Voclosporin) softgel capsules and matching Placebo capsules will be supplied in cartons containing 168 capsules in 4 wallets of 42 capsules each 

None

Randomized

Double Blind

Should emergency unblinding be required, the Investigator should call the Worldwide Clinical Trials (WCT) Medical Monitor before unblinding wherever possible; however, the Investigator is responsible for the medical care of the individual study subject, and does not require the agreement of the Medical Monitor before unblinding. The reason for unblinding must be documented. The information on study treatment should only be used for decision making in the subject’s further treatment. Details on unblinded treatment assignments should not be shared with the Study Monitor and project team.

Not Applicable

To assess the efficacy of Orelvo (Voclosporin) compared with placebo in achieving renal response after 24 weeks of therapy in subjects with active LN

Phase III

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