Clinical trial NCT06666491: An Interventional Study to Compare the Efficacy and Safety of Tafenoquine (TQ) and Primaquine (PQ) When Either Are Taken Together With Chloroquine (CQ) for the Treatment of P. Vivax Malaria in Indian Participants Aged 2 Years and Older
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Malaria, Vivax
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2024-10-30
Enrollment: 300
Sex: ALL
Minimum age (years): 2
Maximum age (years): 64
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of this study is to collect efficacy and safety data to support the registration of tafenoquine in India.


Eligibility criteria: Inclusion Criteria:

1. Males and females \>=2 years of age and under (\<) 65 years of age, weighing \>10 kg.
2. The participant has a positive malarial smear for P. vivax with a parasite density of \>100/microliter and \<100,000/microliter.
3. The participant has a screening Hb value \>8 g/dL.
4. The participant has an axillary temperature of 37.5°C or history of fever 48 hours before recruitment.
5. The participant has a G6PD value (measured using the SD Biosensor STANDARDTM G6PD test) 6.1 units/gram (U/g) Hb for G6PD activity (6.1 U/g Hb cut-off is applicable for both males and females).
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
   * Is a Women of Childbearing Potential (WOCBP) and using a contraceptive method that is highly effective (with a failure rate of \<1% per year), with low user dependency, during the study intervention period and for at least 90 days after the last dose of study intervention. The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first dose of study intervention. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
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.

Exclusion Criteria:

1. The participant has severe P. vivax malaria as defined by WHO criteria \[WHO, 2023\].
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) \>450 msec, evidence of bradycardia (\<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 (\<2.9 millimoles per liter \[mmol/L\]) or hyperkalemia (\>=6.0 mmol/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:

    1. Histamine-2 blockers (restricted to first 3 days whilst receiving CQ)
    2. Antacids (restricted to first 3 days whilst receiving CQ)
    3. Drugs of the biguanide class (i.e., phenformin, metformin, buformin)
    4. Anti-arrhythmic agents (i.e., dofetilide, procainamide, pilsicainide)
    5. Medications that prolong the QTc interval
16. The participant has liver transaminases (ALT/AST) \>2 times the upper limit of normal (ULN).

Primary outcomes:
measure: Number of participants remaining recurrence-free during the 6 months post-treatment and have a negative blood smear at the Month 6 (end of study [EOS]) visit
timeFrame: Up to Month 6
Secondary outcomes:
measure: Number of participants with clinically relevant hemolysis change from baseline
timeFrame: Up to Day 14
measure: Time to recurrence of P. vivax malaria
timeFrame: Up to Month 6
measure: Number of participants with treatment emergent adverse events (TEAEs) up to Month 6
timeFrame: Up to Month 6
measure: Number of participants with TEAEs meeting >= Division of Acquired Immunodeficiency Syndrome (DAIDS) Grade 3 criteria
timeFrame: Up to Month 6
measure: Number of participants with drug related TEAEs
timeFrame: Up to Month 6
measure: Number of participants with serious AEs (SAEs)
timeFrame: Up to Month 6
measure: Number of participants with AEs resulting in treatment discontinuation
timeFrame: Up to Month 6
measure: Number of participants with AEs leading to study withdrawal
timeFrame: Up to Month 6
measure: Number of participants with AEs considered to be hematologically related
timeFrame: Up to Month 6
measure: Number of deaths
timeFrame: Up to Month 6
measure: Liver chemistry changes meeting Hy's criteria
timeFrame: Up to Month 6
measure: Laboratory parameters meeting >= Division of AIDS (DAIDs) Grade 3 criteria
timeFrame: Up to Month 6
measure: Vital sign parameters meeting >=DAIDs Grade 3 criteria
timeFrame: Up to Month 6
measure: Number of participants with TEAEs up to Week 4
timeFrame: Up to Week 4
measure: Change from baseline at each study visit for clinical chemistry parameters (ALT, AST, ALP)
timeFrame: At Days 5, 8, 15, 29, 60, 90, 120, 150 and 180
measure: Change from baseline at each study visit for clinical chemistry parameters (CPK)
timeFrame: At Days 5, 8, 15, 29, 60, 90, 120, 150 and 180
measure: Change from baseline at each study visit for clinical chemistry parameters (total bilirubin, indirect bilirubin, blood urea nitrogen [BUN]/Urea, and serum creatinine)
timeFrame: At Days 5, 8, 15, 29, 60, 90, 120, 150 and 180
measure: Change from baseline at each study visit for clinical chemistry parameters (serum electrolytes)
timeFrame: At Days 5, 8, 15, 29, 60, 90, 120, 150 and 180
measure: Change from baseline at each study visit for haematology parameters (platelet count)
timeFrame: At Days 5, 8, 15, 29, 60, 90, 120, 150 and 180
measure: Change from baseline at each study visit for haematology parameters (red blood cell [RBC] count)
timeFrame: At Days 5, 8, 15, 29, 60, 90, 120, 150 and 180
measure: Change from baseline at each study visit for haematology parameters (mean corpuscular volume [MCV])
timeFrame: At Days 5, 8, 15, 29, 60, 90, 120, 150 and 180
measure: Change from baseline at each study visit for haematology parameters (mean corpuscular hemoglobin [MCH])
timeFrame: At Days 5, 8, 15, 29, 60, 90, 120, 150 and 180
measure: Change from baseline at each study visit for haematology parameters (percentage of reticulocytes)
timeFrame: At Days 5, 8, 15, 29, 60, 90, 120, 150 and 180
measure: Change from baseline at each study visit for haematology parameters (white blood cell count [WBC] with differential)
timeFrame: At Days 5, 8, 15, 29, 60, 90, 120, 150 and 180
measure: Change from baseline at each study visit for haematology parameters (hemoglobin)
timeFrame: At Days 5, 8, 15, 29, 60, 90, 120, 150 and 180
measure: Change from baseline at each study visit for haematology parameters (hematocrit)
timeFrame: At Days 5, 8, 15, 29, 60, 90, 120, 150 and 180
Other outcomes:
Locations:
city: Mumbai
country: India
facility: GSK Investigational Site
city: Surat
country: India
facility: GSK Investigational Site
Study officials:
References: