| CTRI Number |
CTRI/2024/07/071492 [Registered on: 29/07/2024] Trial Registered Prospectively |
| Last Modified On: |
30/08/2024 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Multiple Arm Trial |
|
Public Title of Study
|
A study to compare the efficacy and safety of tafenoquine and primaquine when either are taken together with chloroquine for the treatment of P. vivax malaria in Indian participants aged 2 years and older |
|
Scientific Title of Study
|
A randomized, open-label, multi-center, interventional Phase 3 study of the efficacy and safety of tafenoquine compared to primaquine (both co-administered with chloroquine) for the radical cure (relapse prevention) of Plasmodium vivax (P. vivax) malaria in Indian participants (pediatric and adult population) |
| Trial Acronym |
NIL |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| 208550 Dated 20-Dec-2023 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Anup Pingle |
| Designation |
EVP, Global Health Medical Affairs Physician |
| Affiliation |
GlaxoSmithKline Pharmaceuticals Limited |
| Address |
Dr Annie Besant Road
Worli
Mumbai
400030
Mumbai
MAHARASHTRA
400030
India |
| Phone |
9322161211 |
| Fax |
|
| Email |
anup.s.pingle@gsk.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Anup Pingle |
| Designation |
EVP, Global Health Medical Affairs Physician |
| Affiliation |
GlaxoSmithKline Pharmaceuticals Limited |
| Address |
Dr Annie Besant Road
Worli
Mumbai
400030
MAHARASHTRA
400030
India |
| Phone |
9322161211 |
| Fax |
|
| Email |
anup.s.pingle@gsk.com |
|
Details of Contact Person
Public Query
|
| Name |
Swapnali Raut |
| Designation |
Director, Clinical Operations India |
| Affiliation |
GlaxoSmithKline Pharmaceuticals Limited India |
| Address |
Dr Annie Besant Road
Worli
Mumbai
400030
Dr Annie Besant Road
Worli
Mumbai
400030
Mumbai
MAHARASHTRA
400030
India |
| Phone |
9821415224 |
| Fax |
|
| Email |
swapnali.a.raut@gsk.com |
|
|
Source of Monetary or Material Support
|
| GlaxoSmithKline Pharmaceuticals Limited, Dr Annie Besant Road, Worli, Mumbai, Maharashtra 400030, India |
|
|
Primary Sponsor
|
| Name |
GlaxoSmithKline Research & Development Limited |
| Address |
980 Great West Road, Brentford, Middlesex, TW8 9GS, UK |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
|
Details of Secondary Sponsor
|
| Name |
Address |
| GlaxoSmithKline Pharmaceuticals Limited |
252, Dr Annie Besant Road, Worli, Mumbai, Maharashtra 400030, India |
|
|
Countries of Recruitment
|
India |
Sites of Study
Modification(s)
|
| No of Sites = 5 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Nirav Shah |
Kiran Hospital Multi Super Speciality Hospital & Research Center |
Nr. Sumul Dairy, Surat, Gujarat - 395004
Surat
GUJARAT |
8320117490
drniravrshah@gmail.com |
| Dr Arunasu Talukdar |
Medical College Kolkata |
88, College St, College Square, Kolkata, West Bengal, 700073
Kolkata
WEST BENGAL |
9831222514
dratalukdar@gmail.com |
| Dr Sanjay Kochar |
S.P. Medical College and A.G. of Hospitals |
Department of Medicine, S.P. Medical College and
A.G. of Hospitals, Bikaner - 334003, India
Bikaner
RAJASTHAN |
9460128222
drskkochar@gmail.com |
| Dr Nithya Gogtay |
Seth G S Medical College and KEM hospital |
Department of Clinical Pharmacology, 1st floor New MS building, Seth G S Medical College and KEM hospital, Acharya Donde Marg, Parel, Mumbai 400012
Mumbai
MAHARASHTRA |
9820495836
njgogtay@hotmail.com |
| Dr Leena Dabhi |
Sheth LG Hospital and Narendra Modi Medical College |
Research Room, Ground Floor, Old Building, Sheth LG Hospital, Krushnabaug, Maninagar
Ahmadabad
GUJARAT |
9427609717
Leenadabhilg@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 5 |
| Name of Committee |
Approval Status |
| AMC MET Ethics committee |
Approved |
| INSTITUTIONAL ETHICS COMMITTEE, MEDICAL COLLEGE KOLKATA |
Submittted/Under Review |
| Institutional Ethics Committee, S.P. Medical College |
Submittted/Under Review |
| Institutional Ethics Committee-l, Seth GS Medical College and KEM Hospital |
Submittted/Under Review |
| Kiran Hospital Ethics Committee |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: B51||Plasmodium vivax malaria, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Primaquine |
0.25 mg/kg/day (or an equivalent total dose) Film coated tablet for a period of 14 days |
| Intervention |
Tafenoquine |
150 mg Film coated tablet, single dose on Day 1 |
| Intervention |
Tafenoquine |
Pediatric tablet 50 mg, Fast-dispersing film-coated tablet, single dose on Day 1 based on weight |
|
|
Inclusion Criteria
|
| Age From |
2.00 Year(s) |
| Age To |
65.00 Year(s) |
| Gender |
Both |
| Details |
1. Males and females greater than or equal to 2 years of age and less than 65 years of age, weighing more than 10 kg.
2. The participant has a positive malarial smear for P. vivax with a parasite density of greater than 100 per microliter and less than 100,000 per microliter
3. The participant has a screening Hb value greater than 8 g per dL.
4. The participant has an axillary temperature greater than or equal to 37.5ï€ deg C or history of fever 48 hours before recruitment.
5. The participant has a G6PD value (measured using the SD Biosensor STANDARD G6PD test) greater than 6.1 U per g Hb for G6PD activity.
6. A female participant is eligible to participate if she is not pregnant or breastfeeding, and if one of the following conditions applies:
- Is a woman of non-childbearing potential (WONCBP) as defined in Section
Or
- Is a Women of Childbearing Potential (WOCBP) and using a contraceptive method that is highly effective with low user dependency during the study intervention period and for at least 90 days after the last dose of study intervention..
7. A WOCBP must test negative on a highly sensitive pregnancy test (urine or serum as required by local regulations) before the first dose of study intervention.
8. The participant is willing and able to comply with the procedures described in the study protocol. The participant or parent/legal guardian, as applicable, has given written informed, dated consent; and the participant has given written assent, if applicable, to participate in the study.
|
|
| ExclusionCriteria |
| Details |
1. The participant has severe P. vivax malaria as defined by WHO criteria 2023
2. The participant has a mixed malaria infection (identified by a malarial smear).
3. The participant has a condition that may affect absorption of study medication, such as severe vomiting (no food or inability to take food during the previous 8 hours).
4. The participant has a history of porphyria, psoriasis, or epilepsy.
5. The participant has a history of allergy, intolerance to or a known contraindication to the use of mefloquine (or other aryl amino alcohol drugs), chloroquine, tafenoquine, primaquine, any other 4- or 8-AQ or any of their respective excipients.
6. The participant has received treatment with any investigational drug within 30 days of study entry, or within 5 half-lives, whichever is longer.
7. The participant has previously enrolled in this study.
8. The participant has a recent history of illicit drug abuse or heavy alcohol intake that in the opinion of the investigator could compromise full participation in the study or adherence to study procedures.
9. Participants with a current or past history of serious psychiatric disorders.
10. The participant has a clinically significant concurrent illness (e.g., pneumonia, tuberculosis, meningitis, septicemia, dengue, coagulopathy, severe hemorrhage, or febrile convulsions prior to consent) or a pre-existing condition (e.g., renal disease, malignancy, or severe malnutrition according to WHO child growth standards) or systemic disease predisposing patients to suffer from granulocytopenia, such as rheumatoid arthritis and lupus erythematosus or severe ocular disease.
11. The participant is known to be HIV-infected and or is currently on antiretroviral therapy.
12. The participant is regularly using drugs with hemolytic potential.
13. The participant has a QT corrected by Fridericia’s formula (QTcF) greater than 450 msec evidence of bradycardia (less than 50 beats per min) or ventricular arrhythmias on the screening ECG, a history of cardiac disease (e.g., myocardial infarction, congenital heart disease, or arrhythmia), hypokalemia (less than 2.9 mmol per L) or hyperkalemia (greater than or equal to 6.0 mmol per L) at Screening.
14. The participant has taken drugs with antimalarial activity (e.g., artemisinin-based combination therapies, mefloquine, primaquine, chloroquine, tafenoquine or any other 4-AQ) within 30 days prior to study entry
15. The participant has taken or will likely require during the study the use of:
a. Histamine-2 blockers (restricted to first 3 days whilst receiving CQ)
b. Antacids (restricted to first 3 days whilst receiving CQ)
c. Anti-diabetic drugs of the biguanide class (i.e., phenformin, metformin, buformin)
d. Anti-arrhythmic agents (i.e., dofetilide, procainamide, pilsicainide)
e. Medications that prolong the QTc interval
16. The participant has liver transaminases (ALT, AST) greater than 2 times the upper limit of normal (ULN).
|
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Centralized |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
| To compare the clinical efficacy of TQ and PQ, both co-administered with CQ, for the radical cure of P. vivax malaria in Indian participants with P.vivax malaria aged greater than or equal to 2 years and weighing greater than 10 kg, during 6 months post-treatment (prevention of P. vivax recurrence) |
Participants who remain recurrence-free during the 6 months post-treatment (in the absence of concomitant/rescue medication with activity against P. vivax malaria); defined as clearance of blood-stage parasitemia confirmed by 2 consecutive negative blood smears between Day 2 and Day 8, no positive blood smear for P. vivax parasites at any point during the 6-month follow up period, and a negative P. vivax smear at the 6-month assessment. |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| To assess the occurrence of clinically relevant hemolysis with TQ and PQ co-administered with CQ for the radical cure of P. vivax malaria in Indian participants with P. vivax malaria aged greater than or equal to 2 years and weighing greater than 10 kg |
Participants with clinically relevant hemolysis within the first 14 days after first dose of TQ or PQ defined as a decrease in hemoglobin of greater than or equal to 30 percent or greater than 3g per dL from baseline or an overall drop in hemoglobin below 6.0 g per dL or complications thereof (eg, required transfusions, acute renal failure) |
| To evaluate the time to recurrence of P. vivax malaria for TQ and PQ co-administered with CQ in Indian participants with P. vivax malaria aged greater than or equal to 2 years and weighing greater than 10 kg |
Time to recurrence of P. vivax malaria, with recurrence defined as a positive blood smear for P. vivax parasites within the 6-month follow-up period, after initial clearance of blood-stage parasitemia (2 consecutive negative blood smears between Day 2 and Day 8). |
| To evaluate the safety of TQ and PQ co-administered with CQ for the radical cure of P. vivax malaria in Indian participants with P.vivax malaria aged greater than or equal to 2 years and weighing greater than 10 kg. |
Incidence of the following safety parameters during the 6 month follow-up period, AEs, TEAEs, SAEs, changes in vital signs and lab parameters. |
|
|
Target Sample Size
|
Total Sample Size="300"
Sample Size from India="300"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 3 |
|
Date of First Enrollment (India)
|
02/09/2024 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="1"
Months="3"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Open to Recruitment |
|
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
|
| The purpose of the study is to compare the efficacy and safety of tafenoquine and primaquine when either are taken together with chloroquine for the treatment of P. vivax malaria in Indian participants aged 2 years and older. The total duration for each patient is 180 days. | |