Visceral LeishmaniasisPhase 3NCT03129646
Miltefosine/Paromomycin Phase III Trial for Treatment of Primary Visceral Leishmaniasis (VL) Patients in Eastern Africa
A Phase 3 study testing Miltefosine, Paromomycin and Sodium stibogluconate in people with Visceral Leishmaniasis, run by Drugs for Neglected Diseases at 7 sites in 4 countries.
Trial summary
This is an open label, Phase III, randomized, controlled, parallel arm multicentre non-inferiority clinical trial to compare the efficacy and safety of two combination regimens of Miltefosine and Paromomycin with the standard SSG-PM for the treatment of primary adult and children VL patients in Eastern Africa. Read more about this study
- Who is it for?
- Ages 4 to 50 years
- Conditions the study is for
- Visceral Leishmaniasis
- What is being tested?
- Miltefosine, Paromomycin and Sodium stibogluconate
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 439 participants
- Where
- 7 sitesin 4 countries
- Study dates
- 24 Jan 2018to 11 Dec 2020
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 50 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 15Show fewer
- 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)
Trial locations and contacts
7 sites in 4 countries.
7 sites in 4 countries
Sudan3 sites
El Hassan Centre for Tropical Medicine
Doka, Al Qaḑārif
Tabarak Allah MSF Hospital
Gedaref, Al Qaḑārif
Um El Kher Hospital
Gedaref
Ethiopia2 sites
Abdurafi MSF Health Center
Ābderafī, Amhara
University Hospital of Gondar
Gonder
About this study
Official 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
This is an open label, Phase III, randomized, controlled, parallel arm multicentre non-inferiority clinical trial to compare the efficacy and safety of two combination regimens of Miltefosine and Paromomycin with the standard SSG-PM for the treatment of primary adult and children VL patients in Eastern Africa.
Read the detailed description
The 2 treatment regimens to be tested are:
- Arm 1: Paromomycin 20 mg/kg/d IM for 14 days combined with oral miltefosine allometric dosing for 14 days
- Arm 2: Paromomycin 20 mg/kg/d IM for 14 days combined with oral miltefosine allometric dosing for 28 days (recruitment in this arm was discontinued under protocol v4.0 dated 22 Jul 2019)
The reference arm is the current standard treatment for VL:
- Arm 3: Sodium Stibogluconate 20 mg/kg/day IM/IV combined with Paromomycin 15 mg/kg/day IM for 17 days
The target population will be VL patients from 4 to 50 years old in order to cover both paediatric and adult population.
Patients will be hospitalized for 14 days of PM and MF treatment for both arm 1 and arm 2. MF treatment will start at the same time as PM treatment and for arm 2 it will continue on an out-patient basis until completion of the 28 days treatment.
SSG\&PM combination therapy will be administered for 17 days according to routine VL treatment guidelines and patients will remain hospitalized for the entire duration of the treatment.
All patients will be asked to return to the hospital for a full assessment on day 28, and for followup visits on day 56 and at six months.
To respond to the objectives, study assessments will be carried out at screening and on days 1, 3, 7, 14, 21, 28, 56 (one-month post-treatment) and 210 (six-month post-treatment). These assessments will include clinical, parasitological, haematological, biochemistry, safety, pharmacokinetic and pharmacodynamics assessments.
- Conditions
- Visceral Leishmaniasis
- Being tested
- Miltefosine, Paromomycin, Sodium stibogluconate
- Medical subject headings
- Leishmaniasis, Visceral
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MiltefosineDrug
Also called Impavido
Miltefosine 10mg and 50mg capsules
ParomomycinDrug
Also called Paromomycin sulfate
Paromomycin sulfate equiv to 750mg paromomycin / 2ml amp
Sodium stibogluconateDrug
Also called SSG
Sodium stibogluconate 33% 30 ml inj.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 - MF/PM 14d | Experimental | Paromomycin 20 mg/kg/d IM for 14 days combined with oral miltefosine allometric dosing for 14 days Receives: Drug: Miltefosine; Drug: Paromomycin |
| Arm 2 - MF 28d/PM 14d | Experimental | Paromomycin 20 mg/kg/d IM for 14 days combined with oral miltefosine allometric dosing for 28 days Receives: Drug: Miltefosine; Drug: Paromomycin |
| Arm 3 - SSG/PM 17d | Active comparator | Sodium Stibogluconate 20 mg/kg/day IM/IV combined with Paromomycin 15 mg/kg/day IM for 17 days Receives: Drug: Paromomycin; Drug: Sodium stibogluconate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Definitive Cure
Cure at 6 months follow up defined as absence of clinical signs and symptoms of VL at D210 and no requirement for rescue treatment during the trial (e.g. no relapse or initial treatment failure).
Measured: 6 months follow-up (Day 210)
Secondary outcomes (5)
Incidence of Treatment-Emergent Adverse Events
- Frequency of SAEs and AEs requiring treatment discontinuation
- Frequency and severity of adverse events from the start of treatment through the last visit, at day 210.
Measured: From Screening to day 210
Initial cure at day 28
Initial cure: cure at the end of treatment (Day 28), defined as recovery of clinical signs and symptoms; absence of parasites (microscopy) and no rescue treatment administered up to and including Day 28.
Probable cure: absence of clinical signs and symptoms of VL at D56 and no prior requirement for rescue medication.
Measured: Initial cure: day 28; Probable cure: day 56
Pharmacokinetics of paromomycin and miltefosine
Total and partial blood plasma exposure to paromomycin and miltefosine defined as the area under the concentration-time curve
Measured: During treatment, at 1 month (day 56) and 6 months (day 210) follow-up
Pharmacodynamics
Blood parasite clearance over time (qualitative and quantitative), as measured by qPCR from blood samples
Measured: From baseline until day 210, and at any suspicion of relapse during the trial.
Compliance to miltefosine treatment in an outpatient setting
Compliance to MF treatment in an outpatient setting will be assessed through patients' hospital records history, drug accountability and PK measurements.
Measured: Day 15 to day 28 miltefosine treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2017
- Study start24 Jan 2018
- Primary completion11 Dec 2020
- Study completion11 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Visceral LeishmaniasisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 439 participants (actual)
Sponsor and investigators
- Lead sponsor
- Drugs for Neglected Diseases
- Sponsor type
- University, hospital or other
- Collaborators
- The Netherlands Cancer Institute, The Institute of Endemic Diseases (IEND), University of Khartoum, Kenya Medical Research Institute, Makerere University, University of Gondar
- Responsible party
- Sponsor
- Investigators
- Jane Mbui, MD, Principal investigator, Kenya Medical Research InstituteJoseph Olobo, MD, Prof, Principal investigator, College of Health Sciences, Makerere University, UgandaAhmed M Musa, MD, Prof, Principal investigator, Institute of Endemic Diseases, SudanRezika Mohammed, MD, Principal investigator, University Hospital of Gondar, Ethiopia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03129646
- Sponsor's protocol ID
- DNDi-MILT/PM-01-VL
- Status last verified
- Jul 2020
- First submitted
- 21 Apr 2017
- Last updated
- 29 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Musa AM, Mbui J, Mohammed R, Olobo J, Ritmeijer K, Alcoba G, Muthoni Ouattara G, Egondi T, Nakanwagi P, Omollo T, Wasunna M, Verrest L, Dorlo TPC, Musa Younis B, Nour A, Taha Ahmed Elmukashfi E, Ismail Omer Haroun A, Khalil EAG, Njenga S, Fikre H, Mekonnen T, Mersha D, Sisay K, Sagaki P, Alvar J, Solomos A, Alves F. Paromomycin and Miltefosine Combination as an Alternative to Treat Patients With Visceral Leishmaniasis in Eastern Africa: A Randomized, Controlled, Multicountry Trial. Clin Infect Dis. 2023 Feb 8;76(3):e1177-e1185. doi: 10.1093/cid/ciac643.
PubMed 36164254
Study at a glance
From the registry record, last updated by the sponsor on 29 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT03129646
- Acronym / sponsor ID
- DNDi-MILT/PM-01-VL
- Conditions
- Visceral Leishmaniasis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 439 participants (actual)
- Lead sponsor
- Drugs for Neglected DiseasesUniversity, hospital or other
- Collaborators
- The Netherlands Cancer Institute, The Institute of Endemic Diseases (IEND), University of Khartoum, Kenya Medical Research Institute, Makerere University, University of Gondar
- Study start
- 24 Jan 2018 (actual)
- Primary completion
- 11 Dec 2020 (actual)
- Study completion
- 11 Dec 2020 (actual)
- First posted
- 26 Apr 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open label, Phase III, randomized, controlled, parallel arm multicentre non-inferiority clinical trial to compare the efficacy and safety of two combination regimens of Miltefosine and Paromomycin with the standard SSG-PM for the treatment of primary adult and children VL patients in Eastern Africa.
Detailed description
The 2 treatment regimens to be tested are:
- Arm 1: Paromomycin 20 mg/kg/d IM for 14 days combined with oral miltefosine allometric dosing for 14 days
- Arm 2: Paromomycin 20 mg/kg/d IM for 14 days combined with oral miltefosine allometric dosing for 28 days (recruitment in this arm was discontinued under protocol v4.0 dated 22 Jul 2019)
The reference arm is the current standard treatment for VL:
- Arm 3: Sodium Stibogluconate 20 mg/kg/day IM/IV combined with Paromomycin 15 mg/kg/day IM for 17 days
The target population will be VL patients from 4 to 50 years old in order to cover both paediatric and adult population.
Patients will be hospitalized for 14 days of PM and MF treatment for both arm 1 and arm 2. MF treatment will start at the same time as PM treatment and for arm 2 it will continue on an out-patient basis until completion of the 28 days treatment.
SSG\&PM combination therapy will be administered for 17 days according to routine VL treatment guidelines and patients will remain hospitalized for the entire duration of the treatment.
All patients will be asked to return to the hospital for a full assessment on day 28, and for followup visits on day 56 and at six months.
To respond to the objectives, study assessments will be carried out at screening and on days 1, 3, 7, 14, 21, 28, 56 (one-month post-treatment) and 210 (six-month post-treatment). These assessments will include clinical, parasitological, haematological, biochemistry, safety, pharmacokinetic and pharmacodynamics assessments.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm 1 - MF/PM 14d | Experimental | Drug: Miltefosine, Drug: ParomomycinParomomycin 20 mg/kg/d IM for 14 days combined with oral miltefosine allometric dosing for 14 days |
| Arm 2 - MF 28d/PM 14d | Experimental | Drug: Miltefosine, Drug: ParomomycinParomomycin 20 mg/kg/d IM for 14 days combined with oral miltefosine allometric dosing for 28 days |
| Arm 3 - SSG/PM 17d | Active comparator | Drug: Paromomycin, Drug: Sodium stibogluconateSodium Stibogluconate 20 mg/kg/day IM/IV combined with Paromomycin 15 mg/kg/day IM for 17 days |
Who may qualify
- Ages
- 4 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MiltefosineAlso: ImpavidoMiltefosine 10mg and 50mg capsules | Drug | Arm 1 - MF/PM 14d, Arm 2 - MF 28d/PM 14d |
| ParomomycinAlso: Paromomycin sulfateParomomycin sulfate equiv to 750mg paromomycin / 2ml amp | Drug | Arm 1 - MF/PM 14d, Arm 2 - MF 28d/PM 14d, Arm 3 - SSG/PM 17d |
| Sodium stibogluconateAlso: SSGSodium stibogluconate 33% 30 ml inj. | Drug | Arm 3 - SSG/PM 17d |
Primary outcome
Definitive Cure
Time frame: 6 months follow-up (Day 210)
Cure at 6 months follow up defined as absence of clinical signs and symptoms of VL at D210 and no requirement for rescue treatment during the trial (e.g. no relapse or initial treatment failure).
5 secondary outcomes
Incidence of Treatment-Emergent Adverse Events
Time frame: From Screening to day 210
Initial cure at day 28
Time frame: Initial cure: day 28; Probable cure: day 56
Pharmacokinetics of paromomycin and miltefosine
Time frame: During treatment, at 1 month (day 56) and 6 months (day 210) follow-up
Pharmacodynamics
Time frame: From baseline until day 210, and at any suspicion of relapse during the trial.
Compliance to miltefosine treatment in an outpatient setting
Time frame: Day 15 to day 28 miltefosine treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Feb 2024.
- Derived from this study: PubMed 36164254Musa AM, Mbui J, Mohammed R, Olobo J, Ritmeijer K, Alcoba G, Muthoni Ouattara G, Egondi T, Nakanwagi P, Omollo T, Wasunna M, Verrest L, Dorlo TPC, Musa Younis B, Nour A, Taha Ahmed Elmukashfi E, Ismail Omer Haroun A, Khalil EAG, Njenga S, Fikre H, Mekonnen T, Mersha D, Sisay K, Sagaki P, Alvar J, Solomos A, Alves F. Paromomycin and Miltefosine Combination as an Alternative to Treat Patients With Visceral Leishmaniasis in Eastern Africa: A Randomized, Controlled, Multicountry Trial. Clin Infect Dis. 2023 Feb 8;76(3):e1177-e1185. doi: 10.1093/cid/ciac643.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jane Mbui, MD principal investigator
Kenya Medical Research Institute
Joseph Olobo, MD, Prof principal investigator
College of Health Sciences, Makerere University, Uganda
Ahmed M Musa, MD, Prof principal investigator
Institute of Endemic Diseases, Sudan
7 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Miltefosine, Paromomycin and Sodium stibogluconate in people with Visceral Leishmaniasis, run by Drugs for Neglected Diseases at 7 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Sudan, Ethiopia, Kenya, Uganda. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Definitive Cure (time frame: 6 months follow-up (Day 210)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03129646, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Feb 2024.