Eval 3-Drug Therapy Diethylcarbamize, Albendazole and Ivermectin That Could Accelerate LF Elimination Outside of Africa

Eval 3-Drug Therapy Diethylcarbamize, Albendazole and Ivermectin That Could Accelerate LF Elimination Outside of Africa

Evaluate Triple-Drug Therapy With Diethylcarbamize (DEC), Albendazole (ALB) and Ivermectin (IVM) That Could Accelerate LF Elimination Outside of Africa

This study will determine if a combination of 3 drugs used to treat the infection that cause lymphatic filariasis (LF) due to Wuchereria bancrofti infection are more effective in killing or sterilizing the adult worms compared to just 2 of the 3 drugs that usually given to treat this infection. The three drugs used together are called albendazole (ALB), ivermectin (IVM) and diethylcarbamazine (DEC). The usual treatment in Papua New Guinea (PNG) for lymphatic filariasis are DEC and ALB. A combination of these 3 drugs has not been previously used to treat LF.

This study will determine whether a single dose of the triple drug regimen of DEC/Iver/Alb is non-inferior to annual treatments with DEC/Alb in inducing sustained clearance of Mf in LF infected subjects (>50 Mf/ml) at 36 months post-treatment. This study also tests the hypothesis that single dose of triple drug is super in sustained clearance of microfilariae compared to single dose of DEC/ALB. There will be 3 treatment arms as follows: The comparator (standard treatment) DEC 6 mg/kg + Alb 400 mg administered annually (at 0, 12, and 24 months). DEC 6 mg/kg + Alb 400 mg given once DEC 6 mg/kg + Alb 400 mg + Iver 200 µg/kg administered once only at the beginning of the RCT (0 month).

Diethylcarbamazine 6 mg/kg + Albendazole 400 mg + Ivermectin 200 µg/kg administered once only at the beginning of the RCT (0 month)

Percent of subjects who become circulating antigen negative at 24 months and 36 months after the beginning of the study

Inclusion Criteria: Men and women 18-65 years >50 mf/ml in finger stick blood samples Willing to give informed consent Exclusion Criteria: Prior treatment for LF within last 5 years Pregnant (do pregnancy test) Hemoglobin < 7 g/dl permanent disability, serious medical illness that prevents or impedes study participation and/or comprehension AST/ALT and creatinine > 1.5 upper limit of normal. Urine dipstick with glucose ≥ 2+ and/or protein ≥ 2+

King CL, Suamani J, Sanuku N, Cheng YC, Satofan S, Mancuso B, Goss CW, Robinson LJ, Siba PM, Weil GJ, Kazura JW. A Trial of a Triple-Drug Treatment for Lymphatic Filariasis. N Engl J Med. 2018 Nov 8;379(19):1801-1810. doi: 10.1056/NEJMoa1706854.

Thomsen EK, Sanuku N, Baea M, Satofan S, Maki E, Lombore B, Schmidt MS, Siba PM, Weil GJ, Kazura JW, Fleckenstein LL, King CL. Efficacy, Safety, and Pharmacokinetics of Coadministered Diethylcarbamazine, Albendazole, and Ivermectin for Treatment of Bancroftian Filariasis. Clin Infect Dis. 2016 Feb 1;62(3):334-341. doi: 10.1093/cid/civ882. Epub 2015 Oct 20.