Phase 1b study of MLN9708 for treatment of lupus nephritis

• Research type

  Research Study

• Full title

  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

• IRAS ID

  148625

• Contact name

  David D'Cruz

• Contact email

  david.d'cruz@kcl.ac.uk

• Sponsor organisation

  Takeda Development Centre Europe Ltd

• Eudract number

  2014-000125-21

• Research summary

  Lupus nephritis (LN) is caused by an autoimmune disease known as systemic lupus erythematosus (SLE) which affects the kidney. This is the most common serious and life-threatening manifestation of SLE and often requires immunosuppressive treatment.

  Although there have been improvements in therapy, only 25-50% of patients achieve disease remission after 2 years of treatment, many experience a relapse within 5 years and 10 to 20% progress to end stage renal disease requiring treatment with either dialysis or kidney transplant.
  
  Ixazomib citrate (MLN9708) is a drug that inhibits protein degradation in cells by blocking the proteasome. Cells that produce antibodies are particularly sensitive to the proteasome inhibition and also very important in causing LN. Ixazomib citrate has been tested in large studies mainly in patients with certain types of cancer involving cells of the immune system and has been found to be safe and well tolerated.

  This is a randomised, double-blind, placebo-controlled safety, tolerability and pharmacokinetic study of multiple rising doses of Ixazomib citrate for treatment of patients with class III or IV LN. Participants will be put into one of 5 treatment groups (A-E). (A) will receive ixazomib citrate consisting of doses of 0.5; (B), 1; (C), 2; (D), 3; and (E), 4 mg or placebo. There will be 6 ixazomib citrate and 2 placebo (which is an inactive substance) patients per cohort.

  Participants will be in the study for approximately 26 weeks. There is a 28 day screening, 84 day treatment and a 3 month Follow-up period. Procedures include: vital signs, electrocardiograms, urine and blood samples for laboratory tests and questionnaires to monitor the disease or side effects of the drug.

  This study is sponsored by Takeda Development Center Europe, Ltd., approximately 40 participants will take part in the study potentially including 4 study sites from the UK.

• REC name

  London - Westminster Research Ethics Committee

• REC reference

  14/LO/1087

• Date of REC Opinion

  1 Jul 2014

• REC opinion

  Favourable Opinion