Efficacy and Safety of Tamibarotene(AM80) for Lupus Nephritis

Lupus Nephritis Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01226147
• Other study ID #: AM80-F01
• Status: Recruiting
• Phase: Phase 2
• First received: October 21, 2010
• Last updated: July 21, 2011
• Start date: September 2010
• Est. completion date: February 2013

Study information

• Verified date: July 2011
• Source: Kinki University
• Contact: Masanori Funauchi, M.D.
• Phone: +81-72-366-0221
• Email: mn-funa[@]med.kindai.ac.jp
• Is FDA regulated: No
• Health authority: Japan: Pharmaceuticals and Medical Devices Agency
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: February 2013
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 75 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Lupus Nephritis
• Nephritis

Intervention

Drug:
• Tamibarotene
4mg/day for 24 weeks.

Locations

Country	Name	City	State
Japan	Kinki University Hospital	Osaka

Sponsors (1)

Lead Sponsor	Collaborator
Kinki University

Country where clinical trial is conducted

Japan, 

References & Publications (1)

Kinoshita K, Kishimoto K, Shimazu H, Nozaki Y, Sugiyama M, Ikoma S, Funauchi M. Successful treatment with retinoids in patients with lupus nephritis. Am J Kidney Dis. 2010 Feb;55(2):344-7. doi: 10.1053/j.ajkd.2009.06.012. Epub 2009 Jul 23. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Renal Function		24 weeks	No
Primary	Urinary Protein values		24 weeks	No
Primary	Urinary Sediment		28 weeks	No
Primary	Anti di-DNA antibody and complement C3		28 weeks	No
Secondary	Disease activity index, total improvement		24 weeks	No
Secondary	SLEDAI		24 weeks	No
Secondary	Safety		28 weeks	Yes