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A Study to Evaluate the Efficacy and Safety of Apremilast in Patients of Chronic and Recurrent Erythema Nodosum Leprosum

NCT04822909 · Status: COMPLETED · Phase: PHASE4 · Type: INTERVENTIONAL · Enrollment: 10

Last updated 2021-03-30

No results posted yet for this study

Summary

Leprosy is a chronic infectious disease caused by Mycobacterium leprae. The disease manifests with a varied spectrum, ranging from localized tuberculoid leprosy (TT) to generalized lepromatous leprosy (LL) types. The normal course of leprosy is interrupted by troublesome immune reactions, namely lepra reactions. ENL (a type 2 lepra reaction) is an immune-mediated hypersensitivity reaction, presenting as erythematous, tender, papulo-nodules and associated with constitutional symptoms (fever, arthralgias etc). Pro-inflammatory mediators are elevated, especially tumour necrosis factor α (TNF-α), interferon-γ (IFN- γ) and interleukins (IL-2, IL-6, IL-12). LL type and high bacteriological index are considered to be risk factors for ENL. Lesions usually appear after starting MDT, although it may also be presenting feature. Diagnosis is made by characteristic lesions associated with constitutional symptoms and painful nerve thickening. Mild episodes of ENL respond to adequate rest and oral aspirin. Severe episodes necessitate anti-inflammatory drugs like corticosteroids (e.g. Prednisolone) and/or thalidomide. Use of high-dose prednisolone increases risk of steroid toxicity. Thalidomide is category X drug (unsafe in pregnancy), not freely available and has cost-limitations. Clofazimine requires higher doses, takes 4 to 6 weeks to be effective and produces gastrointestinal side-effects and skin discoloration. Minocycline has been tried as an alternative; however the drug itself has been reported to precipitate ENL in some patients. Thus, a safe and effective steroid-sparing agent for ENL remains elusive.

Cyclic adenosine monophosphate (cAMP) is an intracellular signal molecule. Phosphodiesterases (PDEs) catalyse degradation of cAMP leading to its inactivation. Inhibition of PDEs leads to increased intracellular cAMP, which has anti-inflammatory actions. PDE-4 isoenzymes are the predominant cAMP degrading enzymes in most immune cells. Apremilast is an oral phosphodiesterase-4 (PDE-4) inhibitor currently used clinically for the treatment of psoriasis and other chronic inflammatory diseases. The anti-inflammatory effects of apremilast shown in-vitro includes downregulating TNF-α, IFN-γ, IL-2, IL-12 and IL-23. Although apremilast is not yet clinically indicated in ENL, its anti-inflammatory spectrum targeting the same molecules as those implicated in ENL and efficacy seen in other inflammatory conditions warrants its trial in chronic, recurrent ENL patients.

Conditions

  • Erythema Nodosum Leprosum

Interventions

DRUG

Apremilast;Apremilast;Apremilast 10 MG; 20 MG; 30 MG Oral Tablet

The study patients will be treated with oral apremilast, administered initially a dose of 10 mg once daily, gradually increasing to reach the maximal therapeutic dosage of 30 mg twice daily before end of 1st week of starting the therapy. The treatment will be continued till 6 months and we will taper the steroids by 10mg/ 2 weeks till 20mg and then 5 mg/ 2 weeks till discontinuation of steroids. If a patient worsens after treatment or develops any serious adverse event after initiation of treatment, he will be withdrawn from the study. If there is no response to the treatment and we are unable to taper steroids after 12 weeks of therapy then the patient will be withdrawn from the study

Sponsors & Collaborators

  • Post Graduate Institute of Medical Education and Research, Chandigarh

    lead OTHER

Principal Investigators

  • Tarun Narang, MD · Post Graduate Institute of Medical Education and Research, Chandigarh

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2019-09-15
Primary Completion
2020-03-14
Completion
2020-06-30

Countries

  • India

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT04822909 on ClinicalTrials.gov