CTRI/2024/11/077429 [Registered on: 27/11/2024] Trial Registered Prospectively
Last Modified On:
10/07/2025
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group, Active Controlled Trial
Public Title of Study
A phase II, multicenter, randomized study to examine effectiveness, safety, and tolerability of ZY-19489 in patients with uncomplicated Plasmodium vivax malaria
Scientific Title of Study
A phase II, multicenter, randomized, assessor-blind, active comparator study to determine the efficacy, safety, and tolerability of orally administered ZY-19489 in patients with uncomplicated Plasmodium vivax malaria
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
ZY-19489.24.002, Version 01 dated 27 May 2024
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Kevinkumar Kansagra
Designation
Sr.General Manager
Affiliation
Zydus Lifesciences Ltd
Address
Zydus Research Center,
Survey No. 396/403, Sarkhej-Bavla National Highway No. 8A
Moraiya, Ahmedabad – 382213, India
Ahmadabad GUJARAT 382213 India
Phone
02717665555
Fax
Email
kevinkumarkansagra@zyduslife.com
Details of Contact Person Scientific Query
Name
Dr Kevinkumar Kansagra
Designation
Sr.General Manager
Affiliation
Zydus Lifesciences Ltd
Address
Zydus Research Center,
Survey No. 396/403, Sarkhej-Bavla National Highway No. 8A
Moraiya, Ahmedabad – 382213, India
GUJARAT 382213 India
Phone
02717665555
Fax
Email
kevinkumarkansagra@zyduslife.com
Details of Contact Person Public Query
Name
Dr Kevinkumar Kansagra
Designation
Sr.General Manager
Affiliation
Zydus Lifesciences Ltd
Address
Zydus Research Center,
Survey No. 396/403, Sarkhej-Bavla National Highway No. 8A
Moraiya, Ahmedabad – 382213, India
GUJARAT 382213 India
Phone
02717665555
Fax
Email
kevinkumarkansagra@zyduslife.com
Source of Monetary or Material Support
Zydus Lifesciences Ltd.
Zydus Research Center,
Survey No. 396/403,
Sarkhej-Bavla National Highway No. 8A Moraiya,
Ahmedabad – 382213, India
Primary Sponsor
Name
Zydus Lifesciences Ltd
Address
Zydus Research Center,
Survey No. 396/403,
Sarkhej-Bavla National Highway No. 8A Moraiya,
Ahmedabad – 382213, India
"D.Y. Patil Medical College Institutional Ethics Committee 5th Floor, Department of Pharmacology, Padmashree D.Y. Patil Medical College and Research Centre, Sector 5, Nerul, Navi Mumbai, Dist. Thane, Maharashtra-400706,India"
Approved
"Institutional Ethics Committee S.N. Medical College, Raja Mandi Near Agra College Agra Central Library, Moti Katra, Mantola, Agra, Uttar Pradesh-282003, India"
Approved
"Institutional Ethics Committee, Guru Teg Bahadur Hospital & UCMS, Dilshad Garden, Delhi, 110095, India. "
Approved
"IPGME&R Research Oversight Committee IPGME&R and SSKM Hospital, 244, A.J.C Bose Road, Kolkata-700020, West Bengal, India "
"Samvedna Hospital Ethics Committee, B27/88G, New Colony, Ravindrapuri , Varanasi-22 I 005, Uttar Pradesh"
Approved
Clinical Research Ethics Committee, School of Tropical Medicine, 108, C.R. Avenue, College Square, Kolkata-700073, West Bengal, India.
Approved
CWS Hospital Institutional Ethics Committee, Community Welfare Society Hospital, Rourkela-769042, India.
Approved
Ethics Committee Brij Medical Centre, Brij Medical Centre Pvt. Ltd., 94. E Panki, Kanpur, UP-208020, India.
Approved
Ethics Committee, Nil Ratan Sircar Medical College and Hospital, 138, A.J.C. Bose Road, Rajabazar, Kolkata-700014, West Bengal, India.
Approved
Father Muller Institutional Ethics Committee, Father Muller Medical College, Father Muller Road,, Kankanady,Mangalore,Karnataka-575002
Approved
Global Ethics Committee, Global Hospital, Global Hospital, 4 Floor Room No. 110,Sarthana, Jakatnaka, Surat, Gujarat-395006, India.
Approved
Hira Mongi Navneet Hospital, Mulund West Mumbai Valaji Ladha Road Mumbai, Mumbai City Maharashtra – 400080, India
Approved
HP Poddar Memorial Clinic and Nursing Home, 56H, Beleghata Main Rd, Subhas Sarobar Park Phool Bagan, Beleghata, Kolkata Kolkata Kolkata West Bengal - 700010 India.
Approved
Institutional Ethics Committee for Human Research, Medical College, Kolkata 88, College Street, Kolkata, West Bengal - 700073, India
Approved
Institutional Ethics Committee of Aayush Hospital, Aayush Hospital, 102-1, 1st Floor, Laxman Arcade Vivekannad, Co-op Hsg 90 Feet Road Dharavi Mumbai City, Maharastra-400017, India.
Approved
MAHE Ethics Committee, Manipal Academy of Higher Education, manipal.edu bldg Madhav Nagar, Manipal Udupi, Karnataka - 576104 India.
Approved
Shrey Hospital Institutional Ethics Committee Shrey Hospital Private Limited, 270/B/5 Near AMCO Bank, Stadium Circle, Navrangpura-380009, Ahmedabad, Gujarat
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: B519||Plasmodium vivax malaria without complication,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
Lariago-DS® (500 mg chloroquine phosphate)
Dose : 500 mg
Route :- Oral
Duration : 3 day therapy
Frequency :- Two tablets as a single initial dose, followed by two tablets again 24 h later and one tablet 48 h later (total course of 5 tablets orally)
Intervention
ZY-19489
Dose:- 900 mg
Route:- Oral
Duration: Single Dose
Frequency : Once on Day 0
Inclusion Criteria
Age From
18.00 Year(s)
Age To
85.00 Year(s)
Gender
Both
Details
1.Ability to swallow oral medication.
2.Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study and that all ques-tions by the participant have been sufficiently answered. For illiterate participants, an impartial witness may sign and date the informed consent document.
3.. Participants who are willing to and are able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
4.Microscopic confirmation of P. vivax (thin and thick blood smear counts of greater than 250 para-sites/microliter)
5. Axillary temperature greater than equal to 37.5°C or history of fever within 24 h of screening
6.Age greater than 18 years and body weight greater than 45 kg
7.Hemoglobin greater than equal to 9 g/dL.
ExclusionCriteria
Details
1.Mixed Plasmodium infection.
2. Signs and symptoms of severe malaria (WHO 2015 criteria see reference list.
3. History of having received any antimalarial treatment (alone or in combination) during the following periods before screening:
-Piperaquine, mefloquine, naphthoquine, or sulfadoxine-pyrimethamine within 6 weeks prior to screening
-Amodiaquine and chloroquine within 4 weeks prior to screening
-Any artemisinin derivative (artesunate, artemether, or dihydroartemisinin), quinine, lumefantrine, or any other antimalarial treatment or antibiotic with antimalarial activity (including cotrimoxazole, tetracyclines, quinolones and fluoroquinolones, and azithromycin) within 14 days prior to screening.
4.Previous participation in any malaria vaccine study or received malaria vaccine in any other circumstances within 3 months of dosing.
5.Known allergy to the study drugs (pyronaridine derivatives/artemisinin derivatives/lumefantrine/chloroquine) and its excipients.
6.Patients who have recently received quinacrine or concurrently receiving other potentially hemolytic drugs or depressants of myeloid elements of the bone marrow.
7.Pregnant or nursing (lactating) women.
8.Sexually active participants not willing to take effective contraception measures; for female participants, oral or injectable contraceptive pills, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, or vasectomized partner.
9.All male participants not intend to use either true abstinence, barrier method, or other effective means of contraception.
10.Participation in other clinical studies within 90 days before first IMP administration and/or during study participation.
11.Severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results, and in the judgment of the investigator, would make the participant inappropriate for entry into this study. Examples would include but not limited to:
-Known Tuberculosis
-Concurrent febrile illness, e.g., Typhoid fever or known or suspected COVID-19 infection
-Immunological disorders (including known or suspected seropositive HIV antibody)
-Severe psychiatric disorders (active depression, recent history of depression, generalised anxiety, psychosis, schizophrenia, or other major psychiatric disorders) and major medical disorders related to cardiovascular, respiratory (including active tuberculosis), renal, gastrointestinal, endocrine, infectious, malignancy, neurological (including auditory) and history of convulsions or other abnormality
-Clinical signs or symptoms of hepatic injury (such as nausea, abdominal pain associated with jaundice) or known severe liver disease (i.e., decompensated cirrhosis, Child-Pugh stage 3 or 4), history of hepatitis B or C, hepatitis B or A vaccination in the last 3 months, known gallbladder or bile duct disease, acute or chronic pancreatitis
-History or family history of long QT syndrome or sudden cardiac death, or any other clinical condition known to prolong the QTc interval, such as history of symptomatic cardiac arrhythmias, clinically relevant bradycardia, or severe heart disease. Use of agents known to prolong the QT interval unless it can be permanently discontinued for the duration of the study
-History of significant renal disorder, such as acute or chronic renal failure
-Any predisposing cardiac conditions for arrhythmia, such as severe hypertension, left ventricular hypertrophy (including hypertrophic cardiomyopathy), or congestive cardiac failure accompanied by reduced left ventricle ejection fraction.
-Systemic disease manifested by tendency to granulocytopenia, such as rheumatoid arthritis and lupus erythematosus.
12.Participants considered at particular risk of receiving an anti-malarial or of participating in the study by the investigator.
13.Inability to comprehend and/or unwillingness to follow the study protocol.
14.Clinical or laboratory evidence of any of the following:
-AST/ALT greater than 3X ULN, regardless of the level of total bilirubin
-Total bilirubin greater than 2X ULN
-Leukocyte count greater than15,000/μL
-QTcF greater than 450 msec
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
An Open list of random numbers
Blinding/Masking
Outcome Assessor Blinded
Primary Outcome
Outcome
TimePoints
To evaluate the efficacy of ZY-19489 as measured by ACPR on Day 28 in Indian symptomatic adults with uncomplicated malaria due to P.vivax monoinfection
Day 28
Secondary Outcome
Outcome
TimePoints
To evaluate the efficacy of ZY-19489 as measured by crude ACPR on Day 14 in Indian symptomatic adults with P.vivax uncomplicated malaria.
Day 14
To evaluate the safety and tolerability of ZY-19489 in Indian adults with uncomplicated P.vivax malaria.
Baseline to End of study
To evaluate fever clearance
Baseline to End of study
Target Sample Size
Total Sample Size="129" Sample Size from India="129" Final Enrollment numbers achieved (Total)= "129" Final Enrollment numbers achieved (India)="129"
Phase of Trial
Phase 2
Date of First Enrollment (India)
13/02/2025
Date of Study Completion (India)
13/09/2025
Date of First Enrollment (Global)
Date Missing
Date of Study Completion (Global)
Date Missing
Estimated Duration of Trial
Years="1" Months="0" Days="0"
Recruitment Status of Trial (Global)
Not Applicable
Recruitment Status of Trial (India)
Completed
Publication Details
N/A
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
Malaria is the second most common infectious disease globally. Although therapies are available for treating uncomplicated malaria, rising cases of drug resistance pose a big threat to the aim of completely eradicating the parasite. ZY-19489 is a new antimalaria drug developed by Zydus Lifesciences Ltd and is studied both in preclin-ical and clinical settings. Clinical studies have been con-ducted in patients with uncomplicated P. falciparum malaria, and these studies have suggested that ZY-19489 is efficacious as well as safe. Although in vitro evidence suggests that ZY-19489 has activity against blood stages of P. vivax, no clinical evidence is available for the activity of ZY-19489 against P. vivax malaria. Hence, this study aims to examine the efficacy, safety, and tolerability of orally administered ZY-19489 in pa-tients with uncomplicated P. vivax malaria.