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

Sponsor
Post Graduate Institute of Medical Education and Research, Chandigarh
Study ID
NCT04822909
Phase
PHASE4
Status
Completed

Conditions

  • Erythema Nodosum Leprosum

Eligibility Criteria

Sex
ALL
Age
N/A - N/A
Healthy Volunteers
Not accepted

Interventions

  • Apremilast;Apremilast;Apremilast 10 MG; 20 MG; 30 MG Oral Tablet — DRUG
    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 If a patient worsens after treatment or develops any serious adverse event after initiation of treatment, he will be withdrawn from the study.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is no response to the treatment and we are unable to taper steroids after 12 weeks of therapy then the patient will be withdrawn from the study

Study Details

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.

Key Dates

First listed
Mar 30, 2021
Start date
Sep 15, 2019
Status verified
Mar 2021
Primary completion
Mar 14, 2020
Completion
Jun 30, 2020

Study Design

Enrollment
10 participants (actual)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Apremilast group
    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.

Primary Outcome Measure

Efficacy of apremilast in chronic, recurrent erythema nodosum leprosum [ Time Frame: 6 months ]

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