PKDL - Post-Kala-Azar Dermal LeishmanioidPhase 2NCT03399955
Short Course Regimens for Treatment of PKDL (Sudan)
A Phase 2 study testing Paromomycin, Ambisome and Miltefosine in people with PKDL - Post-Kala-Azar Dermal Leishmanioid, run by Drugs for Neglected Diseases at 1 site in Sudan.
Trial summary
This is an open label, randomized non comparative phase II clinical trial conducted on parallel groups, to assess the safety and efficacy of the combination of Paromomycin (20 mg/kg/d) IM for 14 days and Miltefosine (allometric dosing) oral for 42 days, and a combination of AmBisome® (20 mg/kg total dose) IV over 7… Read more about this study
- Who is it for?
- Ages 6 to 60 years
- Conditions the study is for
- PKDL - Post-Kala-Azar Dermal Leishmanioid
- What is being tested?
- Paromomycin, Ambisome and Miltefosine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 110 participants
- Where
- 1 siteSudan
- Study dates
- 9 May 2018to 1 May 2022
- Phase
- Phase 2
- 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 6 to 60 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Confirmed PKDL case by clinical presentation and demonstration of parasites by microscopy in a skin smear or by PCR, with documented stable or progressive disease for at least 6 months or grade 3 PKDL
- Male or Female patients aged 6 to 60 years
- Written voluntarily informed consent is obtained from the patient, or his guardian if the patient is < 18 years old. In the case of minors aged >12 to <18, assent from the children is also needed in addition to the guardian's consent.
Who cannot join
- Patients who had prior treatment of PKDL within the last 1 year
- Pregnant and lactating women and women of childbearing age (12 to 55 years) who do not accept to have a pregnancy test and who do not agree to use contraception during treatment period and for 5 months after the end of treatment.
- Patients with signs and symptoms of severe diseases: defined as suffering from a concomitant severe infection such as TB or any other serious known underlying disease (cardiac, renal, hepatic),
- Severe malnutrition defined by BMI for age WHO reference curves for gender, Z score < -3 for subjects 6 to < 19 years; BMI < 16 for subjects > 19 years old
- Patients with haemoglobin < 5g/dL
- Patients with known skin disease
Show all 15Show fewer
- Patients with abnormal liver function (ALT and AST) tests of more than three times the normal range.
- Patients with total bilirubin levels >1.5 times the upper normal range
- Patients with serum creatinine above the upper limit of normal range
- Patients with serum potassium < 3.5 mmol/L
- Patients with pre-existing clinical hearing loss based on audiometry at baseline
- Patients with a positive HIV test as applicable
- Patients / guardian not willing to participate
- Patients with history of allergy or hypersensitivity to the relevant study drug
- Patients on immunomodulators therapy
Trial locations and contacts
1 site in 1 country.
Sudan1 site, 1 recruiting
- Recruiting
Prof. Elhassan Centre for tropical Medicine
Doka, Al Qaḑārif
Brima Musa, MD
About this study
Official title: An Open Label, Randomized, Parallel Arm Clinical Trial of Two Regimens to Assess the Safety and Efficacy for Treatment of Post Kala-azar Dermal Leishmaniasis (PKDL) Patients in Sudan
This is an open label, randomized non comparative phase II clinical trial conducted on parallel groups, to assess the safety and efficacy of the combination of Paromomycin (20 mg/kg/d) IM for 14 days and Miltefosine (allometric dosing) oral for 42 days, and a combination of AmBisome® (20 mg/kg total dose) IV over 7 days and Miltefosine oral for 28 days (allometric dosing) for the treatment of PKDL patients in Sudan.
- Being tested
- Paromomycin, Ambisome, Miltefosine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ParomomycinDrug
Paromomycin (20 mg/kg/d) IM for 14 days
AmbisomeDrug
Also called Liposomal Amphotericin B
AmBisome® (20 mg/kg total dose) IV over 7 days
MiltefosineDrug
Also called Impavido
Miltefosine oral (allometric dosing) for 42 days (arm 1) or 28 days (arm 2)
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Paromomycin + Miltefosine | Experimental | Paromomycin 20 mg/kg/d IM for 14 days combined with Miltefosine allometric BID PO dosing for 42 days Receives: Drug: Paromomycin; Drug: Miltefosine |
| Arm 2: Ambisome + Miltefosine | Experimental | AmBisome® 5mg/kg/d IV infusion at D1, D3, D5 and D7 (20 mg/kg total dose) combined with Miltefosine allometric BID PO dosing for 28 days Receives: Drug: Ambisome; Drug: Miltefosine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Definitive Cure
definitive cure at 12 months after treatment onset, defined as clinical cure (100% lesions resolution) and no additional PKDL treatment between end of therapy and 12 months follow-up assessment.
Measured: 12 months follow-up assessment
Incidence of treatment-emergent adverse events
Frequency of SAE from start of treatment to 12 months follow-up Frequency and severity of all adverse events Frequency and severity of adverse events that lead to treatment discontinuation
Measured: from start of treatment to 12 month follow-up
Secondary outcomes (5)
Pharmacokinetics of Miltefosine
To assess the maximal accumulation (Cmax) of Miltefosine in the skin at the end of treatment and correlate it with achieved plasma concentrations.
Measured: Miltefosine concentration in the skin will be measured at day 14 and day 42 for MF+PM arm and at day 7 and day 28 for Ambisome+MF arm. Miltefosine concentration in the blood will be measured at day 1, day 7, day 14, day 28, day 42 and 3 month
Pharmacokinetics of Amphotericin B (MF + Ambisome arm only)
To assess the maximal accumulation (Cmax) of Amphotericin B in the skin at the end of treatment and correlate it with achieved plasma concentrations.
Measured: Amphotericin B concentration will be measured in the skin at day 7 and day 28. Amphotericin B concentration in the blood will be measured at day 1 and day 7.
Pharmacokinetics of Paromomycin (MF + Paromomycin arm only)
To assess the maximal accumulation (Cmax) of Paromomycin in the skin at the end of treatment and correlate it with achieved plasma concentrations.
Measured: Paromomycin concentration will be measured in the skin at day 14 and day 42. Paromomycin concentration in the blood will be measured at day 1 and day 14.
Immune Response
To assess the change in immune response during and after end of treatment by measuring cytokines profiles level in the peripheral blood.
Measured: At screening, at day 42 (end of treatment) and at 6 month follow-up
Parasite quantification in blood and skin
Parasites will be quantified in blood and skin, by microscopy and qPCR, to assess the clearance before and after treatment.
Measured: At screening, day 42 (end of treatment), 3 month follow-up, 6 month follow-up and 12 month follow-up.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jan 2018
- Study start9 May 2018
- Primary completion9 May 2021 (estimated)
- Study completion1 May 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for PKDL - Post-Kala-Azar Dermal LeishmanioidStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 110 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Drugs for Neglected Diseases
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03399955
- Sponsor's protocol ID
- DNDi-MILT COMB-02-PKDL
- Status last verified
- Jan 2020
- First submitted
- 7 Dec 2017
- Last updated
- 18 Jan 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Torres A, Younis BM, Alamin M, Tesema S, Bernardo L, Solana JC, Moreno J, Mustafa AA, Alves F, Musa AM, Carrillo E. Differences in the Cellular Immune Response during and after Treatment of Sudanese Patients with Post-kala-azar Dermal Leishmaniasis, and Possible Implications for Outcome. J Epidemiol Glob Health. 2024 Sep;14(3):1167-1179. doi: 10.1007/s44197-024-00270-0. Epub 2024 Jul 15.
PubMed 39007942Younis BM, Mudawi Musa A, Monnerat S, Abdelrahim Saeed M, Awad Gasim Khalil E, Elbashir Ahmed A, Ahmed Ali M, Noureldin A, Muthoni Ouattara G, Nyakaya GM, Teshome S, Omollo T, Ochieng M, Egondi T, Mmbone M, Chu WY, Dorlo TPC, Zijlstra EE, Wasunna M, Alvar J, Alves F. Safety and efficacy of paromomycin/miltefosine/liposomal amphotericin B combinations for the treatment of post-kala-azar dermal leishmaniasis in Sudan: A phase II, open label, randomized, parallel arm study. PLoS Negl Trop Dis. 2023 Nov 21;17(11):e0011780. doi: 10.1371/journal.pntd.0011780. eCollection 2023 Nov.
PubMed 37988402
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label, Randomized, Parallel Arm Clinical Trial of Two Regimens to Assess the Safety and Efficacy for Treatment of Post Kala-azar Dermal Leishmaniasis (PKDL) Patients in Sudan
- ClinicalTrials.gov ID
- NCT03399955
- Acronym / sponsor ID
- DNDi-MILT COMB-02-PKDL
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 110 participants (estimated)
- Lead sponsor
- Drugs for Neglected DiseasesUniversity, hospital or other
- Study start
- 9 May 2018 (actual)
- Primary completion
- 9 May 2021 (estimated)
- Study completion
- 1 May 2022 (estimated)
- First posted
- 17 Jan 2018 (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, randomized non comparative phase II clinical trial conducted on parallel groups, to assess the safety and efficacy of the combination of Paromomycin (20 mg/kg/d) IM for 14 days and Miltefosine (allometric dosing) oral for 42 days, and a combination of AmBisome® (20 mg/kg total dose) IV over 7 days and Miltefosine oral for 28 days (allometric dosing) for the treatment of PKDL patients in Sudan.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1: Paromomycin + Miltefosine | Experimental | Drug: Paromomycin, Drug: MiltefosineParomomycin 20 mg/kg/d IM for 14 days combined with Miltefosine allometric BID PO dosing for 42 days |
| Arm 2: Ambisome + Miltefosine | Experimental | Drug: Ambisome, Drug: MiltefosineAmBisome® 5mg/kg/d IV infusion at D1, D3, D5 and D7 (20 mg/kg total dose) combined with Miltefosine allometric BID PO dosing for 28 days |
Who may qualify
- Ages
- 6 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- Confirmed PKDL case by clinical presentation and demonstration of parasites by microscopy in a skin smear or by PCR, with documented stable or progressive disease for at least 6 months or grade 3 PKDL
- Male or Female patients aged 6 to 60 years
- Written voluntarily informed consent is obtained from the patient, or his guardian if the patient is < 18 years old. In the case of minors aged >12 to <18, assent from the children is also needed in addition to the guardian's consent.
Key exclusion criteria (15 listed)
- Patients who had prior treatment of PKDL within the last 1 year
- Pregnant and lactating women and women of childbearing age (12 to 55 years) who do not accept to have a pregnancy test and who do not agree to use contraception during treatment period and for 5 months after the end of treatment.
- Patients with signs and symptoms of severe diseases: defined as suffering from a concomitant severe infection such as TB or any other serious known underlying disease (cardiac, renal, hepatic),
- Severe malnutrition defined by BMI for age WHO reference curves for gender, Z score < -3 for subjects 6 to < 19 years; BMI < 16 for subjects > 19 years old
- Patients with haemoglobin < 5g/dL
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 |
|---|---|---|
| ParomomycinParomomycin (20 mg/kg/d) IM for 14 days | Drug | Arm 1: Paromomycin + Miltefosine |
| AmbisomeAlso: Liposomal Amphotericin BAmBisome® (20 mg/kg total dose) IV over 7 days | Drug | Arm 2: Ambisome + Miltefosine |
| MiltefosineAlso: ImpavidoMiltefosine oral (allometric dosing) for 42 days (arm 1) or 28 days (arm 2) | Drug | Arm 1: Paromomycin + Miltefosine, Arm 2: Ambisome + Miltefosine |
Primary outcome
Definitive Cure
Time frame: 12 months follow-up assessment
definitive cure at 12 months after treatment onset, defined as clinical cure (100% lesions resolution) and no additional PKDL treatment between end of therapy and 12 months follow-up assessment.
Incidence of treatment-emergent adverse events
Time frame: from start of treatment to 12 month follow-up
Frequency of SAE from start of treatment to 12 months follow-up Frequency and severity of all adverse events Frequency and severity of adverse events that lead to treatment discontinuation
5 secondary outcomes
Pharmacokinetics of Miltefosine
Time frame: Miltefosine concentration in the skin will be measured at day 14 and day 42 for MF+PM arm and at day 7 and day 28 for Ambisome+MF arm. Miltefosine concentration in the blood will be measured at day 1, day 7, day 14, day 28, day 42 and 3 month
Pharmacokinetics of Amphotericin B (MF + Ambisome arm only)
Time frame: Amphotericin B concentration will be measured in the skin at day 7 and day 28. Amphotericin B concentration in the blood will be measured at day 1 and day 7.
Pharmacokinetics of Paromomycin (MF + Paromomycin arm only)
Time frame: Paromomycin concentration will be measured in the skin at day 14 and day 42. Paromomycin concentration in the blood will be measured at day 1 and day 14.
Immune Response
Time frame: At screening, at day 42 (end of treatment) and at 6 month follow-up
Parasite quantification in blood and skin
Time frame: At screening, day 42 (end of treatment), 3 month follow-up, 6 month follow-up and 12 month follow-up.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2020.
- Derived from this study: PubMed 39007942Torres A, Younis BM, Alamin M, Tesema S, Bernardo L, Solana JC, Moreno J, Mustafa AA, Alves F, Musa AM, Carrillo E. Differences in the Cellular Immune Response during and after Treatment of Sudanese Patients with Post-kala-azar Dermal Leishmaniasis, and Possible Implications for Outcome. J Epidemiol Glob Health. 2024 Sep;14(3):1167-1179. doi: 10.1007/s44197-024-00270-0. Epub 2024 Jul 15.
- Derived from this study: PubMed 37988402Younis BM, Mudawi Musa A, Monnerat S, Abdelrahim Saeed M, Awad Gasim Khalil E, Elbashir Ahmed A, Ahmed Ali M, Noureldin A, Muthoni Ouattara G, Nyakaya GM, Teshome S, Omollo T, Ochieng M, Egondi T, Mmbone M, Chu WY, Dorlo TPC, Zijlstra EE, Wasunna M, Alvar J, Alves F. Safety and efficacy of paromomycin/miltefosine/liposomal amphotericin B combinations for the treatment of post-kala-azar dermal leishmaniasis in Sudan: A phase II, open label, randomized, parallel arm study. PLoS Negl Trop Dis. 2023 Nov 21;17(11):e0011780. doi: 10.1371/journal.pntd.0011780. eCollection 2023 Nov.
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Paromomycin, Ambisome and Miltefosine in people with PKDL - Post-Kala-Azar Dermal Leishmanioid, run by Drugs for Neglected Diseases at 1 site in Sudan.
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: status not confirmed, as of the sponsor's last update on 18 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sudan. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Gina M Ouattara, manager (+254 20 3995000, gmouattara@dndi.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Definitive Cure (time frame: 12 months follow-up assessment). The study lists 2 primary outcomes in all. 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 NCT03399955, which also lists 2 linked publications.
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 18 Jan 2020.