Miltefosine/Paromomycin Phase III Trial for Treatment of Primary Visceral Leishmaniasis (VL) Patients in Eastern Africa

• Register: ClinicalTrials.gov
• Last refreshed on: 11 March 2024
• Main ID: NCT03129646
• Date of registration: 21/04/2017
• Prospective Registration: Yes
• Primary sponsor: Drugs for Neglected Diseases
• Public title: Miltefosine/Paromomycin Phase III Trial for Treatment of Primary Visceral Leishmaniasis (VL) Patients in Eastern Africa
• Scientific title: An Open Label, Phase III, Randomized Controlled, Multicentre Non-Inferiority Trial to Compare Efficacy and Safety of Miltefosine and Paromomycin With SSG and PM Combination for Treatment of Primary Visceral Leishmaniasis (VL) Patients in Eastern Africa
• Date of first enrolment: January 24, 2018
• Target sample size: 439
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT03129646
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Ethiopia, Kenya, Sudan, Uganda

Contacts

• Name: Rezika Mohammed, MD
• Affiliation: University Hospital of Gondar, Ethiopia

• Name: Joseph Olobo, MD, Prof
• Affiliation: College of Health Sciences, Makerere University, Uganda

• Name: Ahmed M Musa, MD, Prof
• Affiliation: Institute of Endemic Diseases, Sudan

• Name: Jane Mbui, MD
• Affiliation: Kenya Medical Research Institute

Key inclusion & exclusion criteria

Inclusion Criteria:

- Patients with clinical signs and symptoms of VL and confirmatory parasitological
microscopic diagnosis

- Patients aged 4 to < 50 years who are able to comply with the study protocol.

- Patients for whom written informed consent has been obtained (if aged 18 years and
over) or signed by parents(s) or legal guardian for patients under 18 years of age. In
the case of minors, assent from the children also needs to be obtained as per each
country regulatory requirements

Exclusion Criteria:

- Patients who are relapse cases

- Patients with Para-Kala azar dermal leishmaniasis grade 3

- Patients who have received any anti-leishmanial drugs in the last 6 months

- Patients with severe malnutrition (for children aged <5 years: weight-for-height WHO
reference curves by sex, z score <-3; for children patients 5-18 years: BMI-for-age
WHO reference curves by sex, z score < -3; for adults >18 years: BMI < 16)*

- Patients with positive HIV diagnosis

- Patients with previous history of hypersensitivity reaction or known drug class
allergy to any of the study treatments

- Patients with previous history of cardiac arrhythmia or with a clinically significant
abnormal ECG

- Patients suffering from a concomitant severe infection such as TB, schistosomiasis or
any other serious underlying disease (e.g. cardiac, renal, hepatic) or chronic
condition which would preclude evaluation of the patient's response to study
medication

- Pregnant or lactating women

- Female patients of child bearing age who do not accept to have a pregnancy test done
at screening and/or who do not agree to use contraception from treatment period until
5 months after the end of treatment (see section 15.2)

- Patients with haemoglobin < 5g/dl

- Patients with signs of severe VL according to Investigator's judgement, requiring an
indication for AmBisome therapy based on the clinical manifestations (such as
jaundice, bleeding, edema) and clinically significant abnormalities in the following
laboratory parameters: haemoglobin, WBC, platelets, liver enzymes (ALT and AST), total
bilirubin and creatinine

- Patients with pre-existing hearing loss based on audiometry at baseline

- Patients who cannot comply with the planned scheduled visits and procedures of the
study protocol

- Note: for Ethiopia only: Patients with severe malnutrition (for patients 4-18
years: MUAC cut-off based on MUAC-for-height reference table; for patients > 18
years: MUAC < 170 mm)



Age minimum: 4 Years
Age maximum: 50 Years
Gender: All

Health Condition(s) or Problem(s) studied

Visceral Leishmaniasis

Intervention(s)

Drug: Paromomycin

Drug: Miltefosine

Drug: Sodium stibogluconate

Primary Outcome(s)

Definitive Cure [Time Frame: 6 months follow-up (Day 210)]

Secondary Outcome(s)

Compliance to miltefosine treatment in an outpatient setting [Time Frame: Day 15 to day 28 miltefosine treatment]

Incidence of Treatment-Emergent Adverse Events [Time Frame: From Screening to day 210]

Pharmacodynamics [Time Frame: From baseline until day 210, and at any suspicion of relapse during the trial.]

Pharmacokinetics of paromomycin and miltefosine [Time Frame: During treatment, at 1 month (day 56) and 6 months (day 210) follow-up]

Initial cure at day 28 [Time Frame: Initial cure: day 28; Probable cure: day 56]

Secondary ID(s)

DNDi-MILT/PM-01-VL

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Kenya Medical Research Institute

The Netherlands Cancer Institute

Makerere University

The Institute of Endemic Diseases (IEND), University of Khartoum

University of Gondar