Visceral LeishmaniasisPhase 2NCT00832208
Open-Label, Sequential Step, Safety and Efficacy Study to Determine the Optimal Single Dose of Ambisome for Patients With VL
A Phase 2 study testing Liposomal amphotericin B (Ambisome) in people with Visceral Leishmaniasis, run by Drugs for Neglected Diseases at 3 sites in 2 countries.
Trial summary
This is a phase II/III open, comparative dose trial to find the lowest single dose of AmBisome for the treatment of primary, symptomatic visceral leishmaniasis(VL), in HIV negative patients. Read more about this study
- Who is it for?
- Ages 4 years and older
- Conditions the study is for
- Visceral Leishmaniasis
- What is being tested?
- Liposomal amphotericin B (Ambisome)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 124 participants
- Where
- 3 sitesin 2 countries
- Study dates
- Apr 2009to Mar 2011
- 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 4 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Male and female adults and children aged 4 years or older with no upper age limit (in accordance with manufacturer's instructions)
- Acute, symptomatic, VL proven by parasitological examination of splenic aspirate (or bone marrow aspirate) with initial parasite index of at least 2+
- Haemoglobin >4g/dL
- Fever for more than 2 weeks
- Living within reachable distance of the trial site to enable attendance for follow-up visits
- Written informed consent to participate (for children, by parent or guardian)
- HIV negative status
Who cannot join
- Patients 'in extremis' with signs/symptoms indicative of severe VL
- Patients who have received any anti-leishmanial treatment within the last 6 months
- Patients who have received any investigational (unlicensed) drugs during 6 months before recruitment
- Known underlying chronic disease, such as severe cardiac, pulmonary, renal, or hepatic impairment.
- Renal function tests (serum creatinine) outside the normal range
- Liver function tests more than 3 times the normal range at study entry
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- Platelet count less than 40,000/ mm3
- Known alcohol abuse
- Pregnancy or lactation
- Concomitant acute drug usage for malaria and bacterial infection, pneumonia within last 7 days
- Known hypersensitivity to AmBisome or amphotericin B
- Any other condition which may invalidate the trial
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
About this study
Official title: Open-Label, Sequential Step, Safety and Efficacy Study to Determine the Optimal Single Dose of Ambisome for Patients With Visceral Leishmaniasis
This is a phase II/III open, comparative dose trial to find the lowest single dose of AmBisome for the treatment of primary, symptomatic visceral leishmaniasis(VL), in HIV negative patients. In this trial, the minimum effective dose will be determined in a sequential step, dose escalation design, which minimises the number of patients exposed to low, potentially inadequate doses and provides contemporaneous comparative data against the manufacturer's recommended dose schedule in this indication.
- Conditions
- Visceral Leishmaniasis
- Being tested
- Liposomal amphotericin B (Ambisome)
- Medical subject headings
- Leishmaniasis, Visceral
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Liposomal amphotericin B (Ambisome)Drug
Also called Ambisome
21.0 mg/kg total dose. Given iv as 3mg/kg/day on days 1,2,3,4,5, and 14 and 21
Liposomal amphotericin B (Ambisome)Drug
Also called Ambisome
liposomal amphotericin b given intravenously as single dose at 7.5 mg/kg increasing to 10, 12.5 and 15.0mg/kg depending on results of interim analyses.
| Study group | Role | What they receive |
|---|---|---|
| Ambisome control: | Active comparator | Ambisome, Total dose 21.0 mg given as 7 x 3mg on days 1,2,3,4,5, and 14 and 21 Receives: Drug: Liposomal amphotericin B (Ambisome) |
| Ambisome test | Experimental | Single dose Ambisome in sequence(7.5 / 10.0/ 12.5 / 15.0mg) Receives: Drug: Liposomal amphotericin B (Ambisome) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary efficacy variable is parasitological clearance with no relapse at 6 months post treatment (ie definitive cure) assessed by clinical status and confirmed by splenic or bone marrow aspiration.
Measured: at 6 months post treatment
Secondary outcomes (1)
Parasitological clearance at day 30.
Measured: Day 30
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2009 (estimated)
- Study startApr 2009
- Primary completionSep 2010
- Study completionMar 2011
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 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 124 participants (actual)
Sponsor and investigators
- Lead sponsor
- Drugs for Neglected Diseases
- Sponsor type
- University, hospital or other
- Collaborators
- Addis Ababa University
- Responsible party
- Sponsor
- Investigators
- Sisay Yifru, MD, Principal investigator, Gondar University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00832208
- Sponsor's protocol ID
- AMBI 0106
- Status last verified
- Jan 2016
- First submitted
- 29 Jan 2009
- Last updated
- 21 Jan 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Khalil EA, Weldegebreal T, Younis BM, Omollo R, Musa AM, Hailu W, Abuzaid AA, Dorlo TP, Hurissa Z, Yifru S, Haleke W, Smith PG, Ellis S, Balasegaram M, EL-Hassan AM, Schoone GJ, Wasunna M, Kimutai R, Edwards T, Hailu A. Safety and efficacy of single dose versus multiple doses of AmBisome for treatment of visceral leishmaniasis in eastern Africa: a randomised trial. PLoS Negl Trop Dis. 2014 Jan 16;8(1):e2613. doi: 10.1371/journal.pntd.0002613. eCollection 2014.
PubMed 24454970Edwards T, Omollo R, Khalil EA, Yifru S, Musa B, Musa A, Wasunna M, Smith PG, Royce C, Ellis S, Balasegaram M, Hailu A. Single-dose liposomal amphotericin B (AmBisome(R)) for the treatment of visceral leishmaniasis in East Africa: study protocol for a randomized controlled trial. Trials. 2011 Mar 6;12:66. doi: 10.1186/1745-6215-12-66.
PubMed 21375777
Study at a glance
From the registry record, last updated by the sponsor on 21 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-Label, Sequential Step, Safety and Efficacy Study to Determine the Optimal Single Dose of Ambisome for Patients With Visceral Leishmaniasis
- ClinicalTrials.gov ID
- NCT00832208
- Acronym / sponsor ID
- AMBI 0106
- Conditions
- Visceral Leishmaniasis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 124 participants (actual)
- Lead sponsor
- Drugs for Neglected DiseasesUniversity, hospital or other
- Collaborators
- Addis Ababa University
- Study start
- Apr 2009
- Primary completion
- Sep 2010 (actual)
- Study completion
- Mar 2011 (actual)
- First posted
- 30 Jan 2009 (estimated)
- 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 a phase II/III open, comparative dose trial to find the lowest single dose of AmBisome for the treatment of primary, symptomatic visceral leishmaniasis(VL), in HIV negative patients. In this trial, the minimum effective dose will be determined in a sequential step, dose escalation design, which minimises the number of patients exposed to low, potentially inadequate doses and provides contemporaneous comparative data against the manufacturer's recommended dose schedule in this indication.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ambisome control: | Active comparator | Drug: Liposomal amphotericin B (Ambisome)Ambisome, Total dose 21.0 mg given as 7 x 3mg on days 1,2,3,4,5, and 14 and 21 |
| Ambisome test | Experimental | Drug: Liposomal amphotericin B (Ambisome)Single dose Ambisome in sequence(7.5 / 10.0/ 12.5 / 15.0mg) |
Who may qualify
- Ages
- 4 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Male and female adults and children aged 4 years or older with no upper age limit (in accordance with manufacturer's instructions)
- Acute, symptomatic, VL proven by parasitological examination of splenic aspirate (or bone marrow aspirate) with initial parasite index of at least 2+
- Haemoglobin >4g/dL
- Fever for more than 2 weeks
- Living within reachable distance of the trial site to enable attendance for follow-up visits
Key exclusion criteria (12 listed)
- Patients 'in extremis' with signs/symptoms indicative of severe VL
- Patients who have received any anti-leishmanial treatment within the last 6 months
- Patients who have received any investigational (unlicensed) drugs during 6 months before recruitment
- Known underlying chronic disease, such as severe cardiac, pulmonary, renal, or hepatic impairment.
- Renal function tests (serum creatinine) outside the normal range
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 |
|---|---|---|
| Liposomal amphotericin B (Ambisome)Also: Ambisome21.0 mg/kg total dose. Given iv as 3mg/kg/day on days 1,2,3,4,5, and 14 and 21 | Drug | Ambisome control: |
| Liposomal amphotericin B (Ambisome)Also: Ambisomeliposomal amphotericin b given intravenously as single dose at 7.5 mg/kg increasing to 10, 12.5 and 15.0mg/kg depending on results of interim analyses. | Drug | Ambisome test |
Primary outcome
The primary efficacy variable is parasitological clearance with no relapse at 6 months post treatment (ie definitive cure) assessed by clinical status and confirmed by splenic or bone marrow aspiration.
Time frame: at 6 months post treatment
1 secondary outcome
Parasitological clearance at day 30.
Time frame: Day 30
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jan 2016.
- Derived from this study: PubMed 24454970Khalil EA, Weldegebreal T, Younis BM, Omollo R, Musa AM, Hailu W, Abuzaid AA, Dorlo TP, Hurissa Z, Yifru S, Haleke W, Smith PG, Ellis S, Balasegaram M, EL-Hassan AM, Schoone GJ, Wasunna M, Kimutai R, Edwards T, Hailu A. Safety and efficacy of single dose versus multiple doses of AmBisome for treatment of visceral leishmaniasis in eastern Africa: a randomised trial. PLoS Negl Trop Dis. 2014 Jan 16;8(1):e2613. doi: 10.1371/journal.pntd.0002613. eCollection 2014.
- Derived from this study: PubMed 21375777Edwards T, Omollo R, Khalil EA, Yifru S, Musa B, Musa A, Wasunna M, Smith PG, Royce C, Ellis S, Balasegaram M, Hailu A. Single-dose liposomal amphotericin B (AmBisome(R)) for the treatment of visceral leishmaniasis in East Africa: study protocol for a randomized controlled trial. Trials. 2011 Mar 6;12:66. doi: 10.1186/1745-6215-12-66.
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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.
Sisay Yifru, MD principal investigator
Gondar University
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Liposomal amphotericin B (Ambisome) in people with Visceral Leishmaniasis, run by Drugs for Neglected Diseases at 3 sites in 2 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 7 inclusion and 12 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: stopped early, as of the sponsor's last update on 21 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Ethiopia, 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?
The study was stopped early. Results are not available in the source record.
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?
The primary efficacy variable is parasitological clearance with no relapse at 6 months post treatment (ie definitive cure) assessed by clinical status and confirmed by splenic or bone marrow aspiration. (time frame: at 6 months post treatment). 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 NCT00832208, 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 21 Jan 2016.