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Efficacy and Safety of Tamibarotene(AM80) for Lupus Nephritis

This study is currently recruiting participants.
Verified July 2011 by Kinki University
Sponsor:
Information provided by:
Kinki University
ClinicalTrials.gov Identifier:
NCT01226147
First received: October 21, 2010
Last updated: July 21, 2011
Last verified: July 2011
History of Changes
  Purpose

An open-label study to evaluate the efficacy and safety of orally administered Tamibarotene to patients of Lupus Nephritis


Condition Intervention Phase
Lupus Nephritis
 Drug: Tamibarotene
 Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment

Further study details as provided by Kinki University:

Primary Outcome Measures:
  • Renal Function [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Urinary Protein values [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Urinary Sediment [ Time Frame: 28 weeks ] [ Designated as safety issue: No ]
  • Anti di-DNA antibody and complement C3 [ Time Frame: 28 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Disease activity index, total improvement [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • SLEDAI [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Safety [ Time Frame: 28 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 20
Study Start Date: September 2010
Estimated Study Completion Date: February 2013
Estimated Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Tamibarotene
    4mg/day for 24 weeks.
Detailed Description:

Tamibarotene is a synthetic retinoid presently approved in Japan for the treatment of APL, and in US, Europe and China it is still under development for APL. Compared to other retinoid drugs available, Tamibarotene has not just a higher activity as a retinoid, but also shows a higher receptor selectivity towards the Retinoic Acid Receptor (RAR) subtypes alfa and beta, but not gamma. All trans retinoic acid (ATRA) and its derivatives are usually pan-agonists to these subtypes, and often are know for the irritation to the skin as one of their major side effects which is due to the RAR gamma subtype. Moreover, unlike ATRA tamibarotene does not cause induction of drug metabolism by CRABP.

Tamibarotene is known to moderate T1/T2 balance as well as Treg/Th17 balance through binding RAR-alfa receptor, and shows efficacy to various autoimmune and inflammatory animal models.

In the preliminary clinical research, patients with lupus nephritis for whom prednisolone treatment was not sufficient enough was treated with oral administration of ATRA to show a remarkable decrease in their protein urea (ref. Kinoshita et al, Am.J.Kidney Dis., 2009 Jul 21).

Based on these results, the investigators plan by this study to evaluate the efficacy of tamibarotene together with the safety to the patients of lupus nephritis.

Tamibarotene is used clinically in Japan since 2005. It's side effects are known to be similar to that of other clinically used retinoids.

  Eligibility

Ages Eligible for Study:   20 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Steroid refractory lupus nephritis

    • more than 10mg of steroid failed to control disease activity
    • patients who failed to reduce the amount of steroid
    • patients who couldn't increase the amount of steroid due to side effects
  • Urine Protein creatinine raio > 0.5 or RBC in urine >= 6 /HPF
  • Anti dsDNA antibody > 10 IU/ml or complement C3 < 84 mg/dl
  • Patients willing to take contraceptive measures throughout the study and for female patients two years after the study and for men six months after the study.

Exclusion Criteria:

  • Pregnant or breastfeeding female patients
  • Hepatic failure patients
  • Triglyceride > 500 mg/dl
  • Patients who started the immunosuppressant therapy or increased the amount of immunosuppressant within 8 weeks prior to test drug administration
  • Patients who received cyclophosphamide puls within 6 months prior to test drug administration
  • Patients with diabetics (HbA1c > 8.0%)
  • Serum creatinine ≧1.5mg/dL
  • CNS( Central Nerve System) Lupus patients
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01226147

Contacts
Contact: Masanori Funauchi, M.D. +81-72-366-0221 mn-funa@med.kindai.ac.jp

Locations
Japan
Kinki University Hospital Recruiting
Osaka, Japan, 5898511
Contact: Masanori Funauchi, M.D.         mn-funa@med.kindai.ac.jp    
Principal Investigator: Masanori Funauchi, M.D.            
Sponsors and Collaborators
Kinki University
  More Information

Publications:

Responsible Party: Masanori Funauchi, MD, Professor, Department of Nephrology and Rheumatology, Kinki University Faculty of Medicine
ClinicalTrials.gov Identifier: NCT01226147     History of Changes
Other Study ID Numbers: AM80-F01
Study First Received: October 21, 2010
Last Updated: July 21, 2011
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by Kinki University:
Lupus Nephritis
SLE
retinoid
tamibarotene

Additional relevant MeSH terms:
Lupus Nephritis
Nephritis
Glomerulonephritis
Kidney Diseases
Urologic Diseases
Lupus Erythematosus, Systemic
Connective Tissue Diseases
 Autoimmune Diseases
Immune System Diseases
Benzoates
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 23, 2013