A Phase II, Multicentre, Randomized, Two-arm Blinded Study to Assess the Efficacy and Safety of Two LXE408 Regimens for Treatment of Patients With Primary Visceral Leishmaniasis

Launched by DRUGS FOR NEGLECTED DISEASES · Oct 20, 2022

Keywords

ClinConnect Summary

This clinical trial is investigating the safety and effectiveness of a new treatment for primary visceral leishmaniasis (VL), a serious disease caused by parasites. The study will compare two different treatment regimens using a medication called LXE408. It’s designed for adults and adolescents aged 12 and older who have been diagnosed with primary VL, which is marked by symptoms like prolonged fever, weight loss, and an enlarged spleen. Participants must be able to provide consent (or have consent provided by a parent or guardian if they are under 18) and should have confirmed VL through specific tests.

If you decide to join this trial, you will be randomly assigned to one of the treatment groups, and neither you nor the researchers will know which group you’re in during the study (this is called a "blinded" study). The trial is also open to people who meet certain health criteria, such as not having severe health issues or other infections that could complicate the study. Participants will be closely monitored for their health and response to the treatment throughout the trial. It's important for potential participants to know that there are specific requirements to ensure their safety and the integrity of the study.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Male and female patients ≥ 18 years (at the time of the screening visit) who are able to comply with the study protocol. Following a favourable interim analysis result, patients ≥12 \<18 years will also be enrolled in the trial
• • Patients for whom written informed consent has been obtained (if aged 18 years and over) or signed by parent(s) or legal guardian for patients under 18 years of age. In the case of minors, assent from the child also needs to be obtained
• • Primary symptomatic VL (defined as typical parameters including, but not limited to, fever for \> 2 weeks, weight loss, and splenomegaly)
• • Visualization of Leishmania amastigotes by microscopy in tissue samples (spleen or bone marrow)
• Exclusion Criteria:
• • Clinical signs of severe VL (jaundice, spontaneous bleeding, edema, ascites, coma, organ failure)
• • Laboratory abnormalities including ALT/SGPT \> 3 times ULN, total bilirubin \> 1.5 times ULN, creatinine \>1.5 times ULN, amylase or lipase \> 1.5 times ULN, haemoglobin \< 6 g/dL or other clinically significant abnormal laboratory parameters which, in the opinion of the investigator, may indicate severe VL
• • Patients with history of previous leishmaniasis and confirmed relapse
• • Patients with para-kala-azar dermal leishmaniasis
• • Patients with severe malnutrition (for children ≥12-\<18 years: BMI-for-age WHO reference curves by sex, z score \< -3; for adults ≥18 years: BMI \< 16)
• • History of congenital or acquired immunodeficiency, including positive HIV (test at screening)
• • Known hypersensitivity to amphotericin B deoxycholate or any other constituents of AmBisome®
• • Concomitant infections such as tuberculosis, severe malaria, or any other serious underlying disease that may interfere with the disease assessment (e.g., cardiac, renal, hepatic, haematologic, and pancreatic)
• • Infection with hepatitis B (HBV) or hepatitis C virus (HCV). A positive HBV surface antigen (HBsAg) test, or if standard local practice, a positive HBV core antigen test, excludes a subject. Patients with a positive HCV antibody test should have HCV RNA levels measured. Patients with positive (detectable) HCV RNA should be excluded.
• • Pregnant or nursing (lactating) women
• • Women of childbearing potential who do not accept to have a pregnancy test done at screening and/or who do not agree to use highly effective contraception while taking the investigational drug and for 5 half-lives or 5 days, whichever is longer, after stopping the investigational drug.
• • Sexually active males unwilling to use a condom during intercourse while taking the investigational drug and for 5 half-lives or 5 days, whichever is longer, after stopping the investigational drug.