Study Stopped
Insufficient enrollment, no safety or efficacy concerns
Safety, Tolerability and Pharmacokinetics of Multiple Rising Doses of Ixazomib in Lupus Nephritis (LN)
A Phase 1b, Randomized, Double-Blind, Placebo-Controlled, Safety, Tolerability and Pharmacokinetic Study of Multiple Rising Doses of MLN9708 for the Treatment of Subjects With ISN / RPS Class III or IV Lupus Nephritis
4 other identifiers
interventional
12
7 countries
35
Brief Summary
The purpose of this study is to characterize the safety and tolerability of ixazomib when administered as multiple oral doses at escalating dose levels in participants with lupus nephritis.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Jun 2014
Typical duration for phase_1
35 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
June 9, 2014
CompletedFirst Submitted
Initial submission to the registry
June 25, 2014
CompletedFirst Posted
Study publicly available on registry
June 27, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 30, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
January 19, 2018
CompletedResults Posted
Study results publicly available
April 8, 2019
CompletedApril 8, 2019
January 1, 2019
2.8 years
June 25, 2014
January 11, 2019
January 11, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
Percentage of Participants Who Experienced at Least One Grade Greater Than or Equal to (>=) 2 Treatment Emergent Adverse Event (TEAE)
Baseline up to Day 101 (30 days after last dose of study drug)
Percentage of Participants Who Experienced at Least One Treatment Emergent Serious Adverse Event (SAE)
Baseline up to Day 101 (30 days after last dose of study drug)
Percentage of Participants Who Experienced at Least One AE Leading to Study Drug Discontinuation
Baseline up to Day 168
Percentage of Participants With at Least One Markedly Abnormal Value (MAV) for Hematologic Parameters
Baseline up to Day 168
Secondary Outcomes (6)
Change From Baseline in Urine Protein to Creatinine Ratio (UPCR) at Day 84
Baseline and Day 84
Change From Baseline in Serum Creatinine (sCR) Level at Day 84
Baseline and Day 84
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Day 84
Baseline and Day 84
Change From Baseline in Levels of Autoantibodies (Anti-double-stranded Deoxyribonucleic Acid [dsDNA]) at Day 84
Baseline and Day 84
Change From Baseline in Complement Protein C3 and C4 at Day 84
Baseline and Day 84
- +1 more secondary outcomes
Study Arms (5)
Cohort A: Ixazomib 0.5 milligram (mg)
EXPERIMENTALIxazomib 0.5 mg, capsules, orally, once, on Day 1, 8 and 15 in 28-day cycles, Cycles 1 through 3.
Cohort B: Ixazomib 2 mg
EXPERIMENTALIxazomib 2 mg, capsules, orally, once, on Day 1, 8 and 15 in 28-day cycles, Cycles 1 through 3.
Cohort C: Ixazomib 3 mg
EXPERIMENTALIxazomib 3 mg, capsules, orally, once, on Day 1, 8 and 15 in 28-day cycles, Cycles 1 through 3.
Cohort D: Ixazomib 4 mg
EXPERIMENTALIxazomib 4 mg, capsules, orally, once, on Day 1, 8 and 15 in 28-day cycles, Cycles 1 through 3.
Cohorts A through D: Placebo
PLACEBO COMPARATORIxazomib placebo-matching capsules, orally, once on Days 1, 8 and 15 in 28-day cycle, Cycles 1 through 3.
Interventions
Eligibility Criteria
You may qualify if:
- In the opinion of the investigator, is capable of understanding and complying with protocol requirements.
- The participant or, when applicable, the participant's legally acceptable representative signs and dates a written informed consent form and any required privacy authorization prior to the initiation of any study procedures.
- Is female or male and aged 18 to 75 years, inclusive.
- Has a diagnosis of systemic lupus erythematosus (SLE) defined by meeting either the 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria or the American College of Rheumatology (ACR) criteria for the classification of SLE. The 4 criteria required by ACR classification are not required to be present at Screening for eligibility.
- Has a definite diagnosis of LN based on a kidney biopsy done within 2 year of the Screening Visit which demonstrated International Society of Nephrology/Renal Pathology Society (ISN/RPS) class III, IV or V changes \[excluding Class III (C), IV-S (C) and IV-G (C)\] or World Health Organization (WHO) 1982 classification Class III,IV or V(excluding Class IIIc and IVd).
- If no biopsy was done within 2 year of Screening Visit, biopsy can be done during the screening period as a study procedure.
- Co-existence of classes is permitted.
- Has a renal biopsy demonstrating either ISN/RPS or WHO class V or class V with class 2 nephritis with a UPCR of greater than (\>) 3 or the participant has a renal biopsy demonstrating either active ISN/RPS or WHO class III or IV nephritis, defined by either one of the following criteria:
- a) A UPCR\* of \>=1.0 at Screening OR b) A UPCR\* \>0.5 at Screening and at least one of the following: i. Active urine sediment in the absence of infection or other cause within 3 months of screening, defined as at least one of the following:
- \>=5 red blood cells (RBC) per high power field, not due to causes other than lupus nephritis.
- \>=5 white blood cells (WBC) per high power field in the absence of infection.
- Presence of cellular casts. ii. The participant has increased levels (above upper limit of normal \[ULN\]) serum dsDNA autoantibodies at screening.
- iii. Low complement (either C3 or C4) at Screening (\>= 25 percent \[%\] lower than lower limit of normal \[LLN\]).
- iv. Biopsy within 3 months prior to screening visit indicating active proliferative lupus glomerulonephritis ISN/RPS class III or IV changes \[excluding Class III (C), IV-S (C) and IV-G (C)\] or WHO 1982 classification Class III or IV (excluding Class IIIc and IVd), with co-existing Class V permitted.
- Participants may be re-screened once for urinary sediment, proteinuria or complement levels within 2 weeks of the original screening visit.
- +8 more criteria
You may not qualify if:
- Must be receiving Standard of Care (SOC) treatment with an immunosuppressant drug for the treatment of LN (example, MMF, MA or AZA).
- Has received any investigational compound within 30 days or 5 half-lives, whichever is the longer, prior to Screening or is currently participating in another interventional clinical study.
- Has received ixazomib, bortezomib, or another proteasome inhibitor in a previous clinical study or as a therapeutic agent.
- Is a sponsor employee, an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (example, spouse, parent, child, sibling), or may consent under duress.
- Has an autoimmune disease other than SLE as their main diagnosis.
- Has drug-induced SLE.
- Has severe, active central nervous system (CNS) lupus (British Isles Lupus Assessment Group \[BILAG\] A or B).
- Has an estimated eGFR of \<30 milliliter per minute per 1.73 m\^2 (mL/min/1.73m\^2), or is on dialysis, or is expected to have a renal transplant within 1 year of randomization, or has had a renal transplant.
- Has a severe acute infectious disease (example, untreated active tuberculosis (TB), acute viral hepatitis, human immunodeficiency virus (HIV), untreated latent TB, or infections requiring IV anti-microbial treatment within 2 months preceding the Screening Visit.
- Has a history of a malignant disease (except successfully treated basal cell carcinoma, squamous cell carcinoma, or cervical carcinoma in situ) within 5 years prior to Screening.
- Has one of the following laboratory test values:
- IgG\<75% of LLN
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>3 times the central laboratory's ULN
- Bilirubin \>1.5 x ULN (participants with Gilbert Syndrome with a confirmed diagnosis and documented in the subject's medical record will not be excluded based on this criterion).
- Platelets \<75,000 per cubic millimeter (/mm\^3)
- +15 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Takedalead
Study Sites (35)
Unknown Facility
La Jolla, California, United States
Unknown Facility
Upland, California, United States
Unknown Facility
Port Charlotte, Florida, United States
Unknown Facility
Evergreen Park, Illinois, United States
Unknown Facility
Brooklyn, New York, United States
Unknown Facility
Great Neck, New York, United States
Unknown Facility
Manhasset, New York, United States
Unknown Facility
New York, New York, United States
Unknown Facility
Middleburg Heights, Ohio, United States
Unknown Facility
Lancaster, Pennsylvania, United States
Unknown Facility
Charleston, South Carolina, United States
Unknown Facility
Jackson, Tennessee, United States
Unknown Facility
Lille, Nord, France
Unknown Facility
Amiens, Somme, France
Unknown Facility
Paris, France
Unknown Facility
Strasbourg, France
Unknown Facility
Frankfurt am Main, Hesse, Germany
Unknown Facility
Aachen, North Rhine-Westphalia, Germany
Unknown Facility
Düsseldorf, North Rhine-Westphalia, Germany
Unknown Facility
Mainz, Rhineland-Palatinate, Germany
Unknown Facility
Berlin, Germany
Unknown Facility
Essen, Germany
Unknown Facility
Freiburg im Breisgau, Germany
Unknown Facility
Rome, Lazio, Italy
Unknown Facility
Turin, Piedmont, Italy
Unknown Facility
Pisa, Tuscany, Italy
Unknown Facility
Padua, Veneto, Italy
Unknown Facility
Kazan', Russia
Unknown Facility
Kemerovo, Russia
Unknown Facility
Saint Petersburg, Russia
Unknown Facility
Madrid, Madrid, Communidad Delaware, Spain
Unknown Facility
Bilbao, Vizcaya, Spain
Unknown Facility
Madrid, Spain
Unknown Facility
London, London, City of, United Kingdom
Unknown Facility
London, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Director
- Organization
- Takeda
Study Officials
- STUDY DIRECTOR
Medical Director Clinical Science
Takeda
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 25, 2014
First Posted
June 27, 2014
Study Start
June 9, 2014
Primary Completion
March 30, 2017
Study Completion
January 19, 2018
Last Updated
April 8, 2019
Results First Posted
April 8, 2019
Record last verified: 2019-01
Data Sharing
- IPD Sharing
- Will share
Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.