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

Официальное название

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)

Обзор

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

Вмешательства

• Препарат Tafenoquine
  A single dose of TQ will be administered orally on Day 1 or Day 2.
• Препарат Primaquine
  A single dose of PQ will be administered orally, daily, on Day 1 or 2 to Day 14 (or Day 15 if PQ started on Day 2).
• Препарат Chloroquine
  A single dose of CQ will be administered orally, daily, on Days 1 to 3.

Первичные конечные точки

• 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 [Срок оценки: Up to Month 6]

Вторичные конечные точки (12)

• Number of participants with clinically relevant hemolysis change from baseline [Срок оценки: Up to Day 14]
• Time to recurrence of P. vivax malaria [Срок оценки: Up to Month 6]
• Number of participants with treatment emergent adverse events (TEAEs) up to Month 6 [Срок оценки: Up to Month 6]
• Number of participants with TEAEs meeting >= Division of Acquired Immunodeficiency Syndrome (DAIDS) Grade 3 criteria [Срок оценки: Up to Month 6]
• Number of participants with drug related TEAEs [Срок оценки: Up to Month 6]
• Number of participants with serious AEs (SAEs) [Срок оценки: Up to Month 6]
• Number of participants with AEs resulting in treatment discontinuation [Срок оценки: Up to Month 6]
• Number of participants with AEs leading to study withdrawal [Срок оценки: Up to Month 6]
• Number of participants with AEs considered to be hematologically related [Срок оценки: Up to Month 6]
• Number of deaths [Срок оценки: Up to Month 6]
• Liver chemistry changes meeting Hy's criteria [Срок оценки: Up to Month 6]
• Laboratory parameters meeting >= Division of AIDS (DAIDs) Grade 3 criteria [Срок оценки: Up to Month 6]

Критерии участия

Критерии включения

• Males and females >=2 years of age and under (<) 65 years of age, weighing >10 kg.
• The participant has a positive malarial smear for P. vivax with a parasite density of >100/microliter and <100,000/microliter.
• The participant has a screening Hb value >8 g/dL.
• The participant has an axillary temperature of 37.5°C or history of fever 48 hours before recruitment.
• 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).
• 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.
• 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.
• 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.

Критерии исключения

• The participant has severe P. vivax malaria as defined by WHO criteria \[WHO, 2023\].
• The participant has a mixed malaria infection (identified by a malarial smear).
• 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).
• The participant has a history of porphyria, psoriasis, or epilepsy.
• 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.
• The participant has received treatment with any investigational drug within 30 days of study entry, or within 5 half-lives, whichever is longer.
• The participant has previously enrolled in this study.
• 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.
• Participants with a current or past history of serious psychiatric disorders.
• 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.
• The participant is known to be HIV-infected and/or is currently on antiretroviral therapy.
• The participant is regularly using drugs with hemolytic potential.
• 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.
• 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.
• The participant has taken or will likely require during the study the use of:

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Индия · 4 центра

• GSK Investigational Site — Ahmedabad
• GSK Investigational Site — Kolkata
• GSK Investigational Site — Mumbai
• GSK Investigational Site — Surat

Идентификаторы

NCT: NCT06666491 · 208550

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗