Efficacy and Safety of Tamibarotene(AM80) for Lupus Nephritis

Sponsor

Kinki University (Other)

Overall Status

Unknown status

CT.gov ID

NCT01226147

Collaborator

(none)

Enrollment

Location

Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Lupus Nephritis	Drug: Tamibarotene	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Study Start Date :

Sep 1, 2010

Anticipated Primary Completion Date :

Feb 1, 2013

Anticipated Study Completion Date :

Feb 1, 2013

Outcome Measures

Primary Outcome Measures

Renal Function [24 weeks]
Urinary Protein values [24 weeks]
Urinary Sediment [28 weeks]
Anti di-DNA antibody and complement C3 [28 weeks]

Secondary Outcome Measures

Disease activity index, total improvement [24 weeks]
SLEDAI [24 weeks]
Safety [28 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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