NCT04822909

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

Completed Phase 4 Last updated 30 March 2021

What this trial tests

Phase 4 trial testing Apremilast;Apremilast;Apremilast 10 MG; 20 MG; 30 MG Oral Tablet in Erythema Nodosum Leprosum in 10 participants. Completed in 30 June 2020.

Timeline

15 September 2019

Primary endpoint
14 March 2020

30 June 2020

Quick facts

Lead sponsor	Post Graduate Institute of Medical Education and Research, Chandigarh
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	10
Start date	15 September 2019
Primary completion	14 March 2020
Estimated completion	30 June 2020
Sites	3 locations across India

Drugs / interventions tested

• Apremilast;Apremilast;Apremilast 10 MG; 20 MG; 30 MG Oral Tablet — full drug profile →

Conditions studied

• Erythema Nodosum Leprosum — all drugs for Erythema Nodosum Leprosum →

Sponsor

Post Graduate Institute of Medical Education and Research, Chandigarh

Who can join

Eligibility, any sex, with Erythema Nodosum Leprosum. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Role of PDE4 Family in Cardiomyocyte Physiology and Heart Failure.
   Sherstnev I, Judina A, Luciani GB, Ghigo A, et al · · 2025 · cited 2× · PMID 40136709 · DOI 10.3390/cells14060460