Clinical Trial Details (PDF Generation Date :- Fri, 04 Jan 2019 20:47:10 GMT) CTRI Number Last Modified On 25/04/2017 Post Graduate Thesis Type of Trial Type of Study Study Design Public Title of Study Scientific Title of Study CTRI/2017/04/008421 [Registered on: 27/04/2017] - Trial Registered Prospectively No Interventional Drug Randomized, Parallel Group Trial New treatment regimens for treatment of Post Kala Azar Dermal Leishmaniasis patients in and Bangladesh region An Open label, Randomized, Clinical Trial of Two Regimens to Assess the Safety and Efficacy for Treatment of PKDL Patients in the n subcontinent Secondary IDs if Any Secondary ID Identifier Details of Principal Investigator or overall Trial Coordinator (multi-center study) Details Contact Person (Scientific Query) Details Contact Person (Public Query) DNDi-MILT COMB-01-PKDL, version 1, date 09 February 2017 Protocol Number Details of Principal Investigator Prof Shyam Sundar Principal Investigator Phone 5422369632 Institute of Medical Sciences, Banaras Hindu University Professor of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi - 221 005, Varanasi UTTAR PRADESH 221005 drshyamsundar@hotmail.com Details Contact Person (Scientific Query) Dr Vishal Goyal Phone 45501795 Senior clinical Manager Drugs for Neglected Diseases initiative Drugs for Neglected Diseases initiative, PHD Chambers, 4/2 Siri Institutional Area New Delhi DELHI 110016 New Delhi DELHI 110016 vgoyal@dndi.org Details Contact Person (Public Query) Dr Vishal Goyal Senior clinical Manager Drugs for Neglected Diseases initiative Drugs for Neglected Diseases initiative, PHD Chambers, 4/2 Siri Institutional Area New Delhi DELHI 110016 New Delhi DELHI 110016 page 1 / 5
Source of Monetary or Material Support Primary Sponsor Details of Secondary Sponsor Countries of Recruitment Sites of Study Details of Ethics Committee Regulatory Clearance Status from DCGI Health Condition / Problems Studied Intervention / Comparator Agent Phone 45501795 vgoyal@dndi.org Source of Monetary or Material Support > Drugs for Neglected Diseases initiative (DNDi, Chemin Louis Dunant, 15, 1202 Geneva, Switzerland Type of Sponsor NIL List of Countries Bangladesh of Principal Investigator Prof Shyam Sundar Dr Krishna Pandey Primary Sponsor Details Drugs for Neglected Diseases initiative DNDi 15, Chemin Louis-Dunant, 1202, Geneva-Switzerland Other [Not for Profit Organisation] NIL of Site Site Phone// Research Centre Rajendra Memorial Medical Sciences Research Centre Rambag Road Muzzarpur, Bihar -842001, Muzaffarpur BIHAR 5422369632 drshyamsundar@hotma il.com Rajendra Memorial 6122631565 Medical Sciences Agam drkrishnapandey@yaho Kuan, Patna, Bihar o.com 800 007, Patna BIHAR of Committee Approval Status Date of Approval Is Independent Ethics Committee? Research Centre - Muzzafarpur Rajendra Memorial Medical Sciences Ethic Committee - Patna Status Not Applicable Health Type Patients Approved 02/04/2017 No Approved 04/03/2017 No Date No Date Specified Condition Post Kala Azar Dermal Leishmaniasis Type Details Intervention Liposomal Amphotericin B (Ambisome ) Ambisome monotherapy regimen (5 x 4 mg/kg IV, twice per week, total dose of 20 mg/kg) Total duration of 15 days (Ambisome injections at D1, D4, D8, D11, D15) page 2 / 5
Inclusion Criteria Intervention Liposomal Amphotericin B (Ambisome ) Miltefosine Comparator Agent Not Applicable Not Applicable Age From Age To Gender Details 6.00 Year(s) 60.00 Year(s) Both Inclusion Criteria Combintaion of Ambisome (5 x 4 mg/kg IV, twice per week, total dose of 20 mg/kg) with miltefosine allometric dose orally for three weeks 1. Confirmed PKDL case by clinical presentation and demonstration of parasites by microscopy in a skin smear or biopsy or by qpcr, with stable or progressive disease for at least 4 months 2. Male or Female patients aged 6 to 60 years 3. Written voluntarily informed consent from adult patient and from parent / guardian in case of children 19-years old 5. Patients with haemoglobin 6. Patients with abnormal liver function (ALT and AST) tests of more than three times the normal range. 7. Patients with total bilirubin levels >1.5 times the upper normal range 8. Patients with serum creatinine above the upper normal range 9. Patients with serum potassium 10. Patients with a positive HIV test as applicable 11. Patients / guardian not willing to participate 12. Patients with history of allergy or hypersensitivity to the relevant study drug 13. Patients on immunomodulators Method of Generating Random Sequence Method of Concealment Blinding/Masking Computer generated randomization Sequentially numbered, sealed, opaque envelopes Open Label Primary Outcome Outcome Timepoints To measure the efficacy (definitive cure at 12 months) of two treatment regimens in subjects with PKDL according to clinical criteria: complete resolution of papular and nodular lesions (flattening of 100% of lesions) and significant improvement ( 80% re-pigmentation) of macular lesions by 12 months after the end of treatment. Follow up patients by 12 months after the end of treatment. Secondary Outcome Outcome Timepoints To assess the maximal accumulation of total Follow up patients by 12 months after the end of amphotericin B and miltefosine in the skin at the treatment. end of treatment and correlate these with plasma levels. To assess the change in immune response during and after end of treatment as compared to baseline by measuring cytokines profiles level in the peripheral blood. To assess the clearance of parasites by microscopy and qpcr at various time-points before, during and after treatment and during follow-up Target Sample Size Total Sample Size=110 page 3 / 5
Phase of Trial Phase 2 Date of First Enrollment () Date of First Enrollment (Global) Estimated Duration of Trial Recruitment Status of Trial (Global) Recruitment Status of Trial () Publication Details Brief Summary Sample Size from =80 20/06/2017 20/06/2017 Years=2 Months=0 Days=0 Not Yet Recruiting Not Yet Recruiting Not Applicable as of now This is a non-comparative, open label, randomized phase II clinical trial to assess the safety and efficacy of Ambisome monotherapy (5 x 4 mg/kg IV given twice per week at a total dose of 20 mg/kg given) and a combination of Ambisome (5 x 4 mg/kg IV given twice per week at a total dose of 20 mg/kg) plus miltefosine orally daily (allometric dosing BID) for three weeks for PKDL patients in and Bangladesh. Participating Sites: In order to have representatives of PKDL patients from different countries, this study will be conducted at 2 sites in Rajendra Memorial Medical Sciences (ICMR Institute) at Patna, Bihar and Research Centre, Muzzafarpur and at one site in Bangladesh - International Centre for Diarrhoeal Disease Research. Study Drugs: Study drugs used in the study are Ambisome and Miltefosine that are currently procured by and being used within the GoI National Programme for treatment of Kala Azar. Both drugs being used in the study have been extensively researched for use in the treatment of visceral leishmaniasis in, and are currently approved and being used by the National Vector Borne Disease Control program for the treatment of Kala Azar. Rationale: This study aims primarily to improve current treatment options. Currently there are no satisfactory treatments for any forms of PKDL. Conventional amphotericin B has been used in for prolonged periods (60 infusions) but this is impractical and requires careful clinical and biochemical monitoring. Both miltefosine and Ambisome as monotherapy have shown to be effective. However, with the current recommended schemes there are some drawbacks such as the length of the treatment with miltefosine alone (12 weeks); the costs and recently observed toxicity of a high dose Ambisome (total dose of 30 mg/kg). There is also the potential risk for development of resistance with miltefosine as monotherapy. PKDL is a disease of major public health importance post- visceral leishmaniasis, as it is thought that PKDL could be a reservoir of Leishmania donovani infection and hence transmit VL. Obviously this is of crucial importance in the current VL elimination efforts in the n subcontinent. The study is being conducted solely to provide better evidence for the GoI in order to treat PKDL patients more effectively as part of the National Kala Azar Elimination Programme. General Objectives: The overall objective of this study is to assess the safety and efficacy of two treatment modalities for PKDL patients in n Subcontinent (ISC). Primary Objective: To measure the safety and efficacy of Ambisome monotherapy regimen (5 x 4 mg/kg IV, twice per week, total dose of 20 mg/kg) and Ambisome (5 x 4 mg/kg IV, twice per week, total dose of 20 mg/kg) in combination with miltefosine orally daily for three weeks (allometric dosing), for PKDL patients in the ISC. Secondary Objectives To assess skin and plasma concentrations of total Ambisome and miltefosine. To evaluate the host immune response in each treatment arm before, during and after page 4 / 5
Powered by TCPDF (www.tcpdf.org) PDF of Trial treatment. To evaluate parasite clearance in each arm as indicated by direct microscopy and qpcr To assess relationship between clinical, parasitological and immunological responses to identify a potential biomarker for cure To assess relationship between pharmacokinetic parameters with clinical outcome and parasite clearance Primary Endpoint Efficacy: To measure the efficacy (definitive cure at 12 months) of two treatment regimens in subjects with PKDL according to clinical criteria: complete resolution of papular and nodular lesions (flattening of 100% of lesions) and significant improvement (> 80% re-pigmentation) of macular lesions by 12 months after the end of treatment. Safety: To assess the safety of the two regimens (SAEs and frequency and severity of AEs) from the start of treatment through the 12-month follow-up period. Secondary Endpoint(s) Pharmacokinetics: To assess the maximal accumulation of total amphotericin B and miltefosine in the skin at the end of treatment and correlate these with plasma levels. Immune Response: To assess the change in immune response during and after end of treatment as compared to baseline by measuring cytokines profiles level in the peripheral blood. Parasitology: To assess the clearance of parasites by microscopy and qpcr at various time-points before, during and after treatment and during follow-up. page 5 / 5