This is a Clinical Study to Assess Whether the Combination of SJ733 and Tafenoquine Will be a Safe and Rapidly Acting Anti-malarial for the Radical Cure of P. Vivax Malaria

NCT07430592 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: 108683PR241297G2022-218
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this Phase 2b study is to examine the safety and efficacy of the combination of SJ733, an investigational agent, and tafenoquine for the radical cure of uncomplicated P. vivax malaria monoinfection in adult participants and determine the contributions of SJ733 to the effect. SJ733 will be administered in a 1-, 2-, or 3-day treatment schedule in combination with a single dose of tafenoquine.

Conditions

Malaria; Malaria Vivax; Radical Cure

Keywords

SJ733; SJ733 with Tafenoquine

Outcome Measures

Primary Outcomes (8)

• Parasitological Recurrence Free survival (RFS)

  Recurrence free survival (RFS), defined as non-relapses of P. vivax at 180 days given parasitemia clearance at 14 days.

  14 - 180 days for each arm

• Clinical Recurrence Free Survival

  Absence of malaria-related clinical signs or symptoms over 180 days following confirmed parasitemia clearance at Day 14.

  14 to 180 days for each arm

• Percentage of patients with treatment related adverse events

  Incidence, severity, drug-relatedness, and seriousness of adverse events

  1 to 180 days for each arm

• Percent of patients with clinically significant abnormal vital signs

  Number of and seriousness of with clinically significant abnormal vital signs including changes from baseline

  1 to 180 days for each arm

• Percent of patients with a decrease in hemoglobin (HB) > 2 g/dL from baseline to an absolute value of <7 g/dL

  Proportion of participants with a decrease in hemoglobin (Hb): \> 2 g/dL from baseline to an absolute value of \< 7 g/dL

  1 to 180 days for each arm

• Percent of patients with an Absolute Neutrophil Count < 1000/μL after baseline

  Proportion of participants with an absolute neutrophil count \< 1,000/μL after baseline

  1 to 180 days for each arm

• Percent of patients with significant changes in ECG findings

  Proportion of participants with significant changes in ECG findings, including heart rate, ECG intervals (PR, QTcB, QTcF), conduction changes or abnormalities

  1 to 180 days for each arm

• Percent of patients with clinically significant increases in venous methemoglobin levels

  Proportion of participants with clinically significant increases in venous methemoglobin levels

  1 to 180 days for each arm

Secondary Outcomes (4)

• Number of participants with signs and symptoms of uncomplicated P. vivax malaria infection

  180 days for each arm

• Parasite clearance Time

  72 hours for each arm

• Area Under the Plasma Concentration Time Curve (AUC)

  180 days

• Maximum Plasma Concentration (Cmax)

  180 days

Other Outcomes (1)

• Correlation between microscopy and PCR measures of parasite clearance kinetics / efficacy

  180 days for each arm

Study Arms (6)

Arm1 - SJ733 600 mg for 3 days and Tafenoquine Placebo

EXPERIMENTAL

SJ733 (600 mg) once a day for 3 consecutive days combined with tafenoquine placebo on the first day

Drug: SJ733/TQ placebo

Arm 2- Chloroquine and Tafenoquine Placebo

EXPERIMENTAL

Chloroquine (600 mg) for 2 consecutive days then Chloroquine (300 mg) for 1 day, combined with tafenoquine placebo on the first day

Drug: CQ/TQ Placebo

Arm 3 - Chloroquine and Tafenoquine

ACTIVE COMPARATOR

Chloroquine (600 mg) for 2 consecutive days then Chloroquine (300 mg) for 1 day, combined with tafenoquine (300 mg) once on the first day

Drug: CQ/TQ

Arm 4a -SJ733 for three days and Tafenoquine

EXPERIMENTAL

SJ733 (600 mg) once a day for 3 consecutive days combined with tafenoquine (300 mg) once on the first day

Drug: SJ733 (3-day)/TQ

Arm 4b - SJ733 for 2 days and Tafenoquine

EXPERIMENTAL

SJ733 (600 mg) once a day for 2 consecutive days, followed by SJ733 placebo for 1 day, combined with tafenoquine (300 mg) once on the first day

Drug: SJ733 (2-day ) /TQ

Arm 4c - SJ733 for one day and Tafenoquine

EXPERIMENTAL

SJ733 (600 mg) once, followed by SJ733 placebo for 2 days, combined with tafenoquine (300 mg) once on the first day

Drug: SJ733(1-day)/TQ

Interventions

SJ733/TQ placebo DRUG

SJ733 combined with Tafenoquine Placebo

Also known as: SJ733, Tafenoquine Placebo

Arm1 - SJ733 600 mg for 3 days and Tafenoquine Placebo

CQ/TQ Placebo DRUG

Chloroquine combined with Tafenoquine Placebo

Also known as: Chloroquine, Tafenoquine Placebo

Arm 2- Chloroquine and Tafenoquine Placebo

CQ/TQ DRUG

Chloroquine combined with Tafenoquine

Also known as: Chloroquine, Tafenoquine

Arm 3 - Chloroquine and Tafenoquine

SJ733 (3-day)/TQ DRUG

SJ733 (3-day schedule) combined with Tafenoquine

Also known as: SJ733, Tafenoquine

Arm 4a -SJ733 for three days and Tafenoquine

SJ733 (2-day ) /TQ DRUG

SJ733 (2-day schedule) combined with Tafenoquine

Also known as: SJ733, Tafenoquine

Arm 4b - SJ733 for 2 days and Tafenoquine

SJ733(1-day)/TQ DRUG

SJ733 (1 day schedule) combined with Tafenoquine

Also known as: SJ733, Tafenoquine

Arm 4c - SJ733 for one day and Tafenoquine

Eligibility Criteria

• Age: 18 Years - 76 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Body weight between 45 kg and 90 kg inclusive.
• Presence of mono-infection of P. vivax confirmed by: Fever, as defined by axillary temperature ≥ 37.5°C or oral/rectal/tympanic temperature ≥ 38°C, or history of fever in the previous 24 hours (history of fever must be documented) and, Microscopically confirmed parasite infection: 1,000 to 40,000 asexual parasite count/µL blood
• Written informed consent provided by participant, in accordance with local practice. If the participant is unable to write, witnessed consent is permitted according to local ethical considerations.
• Ability to swallow oral medication.
• Ability and willingness to participate and to comply with the study requirements.
• Agreement to hospitalization for at least 72 hours and/or until malarial parasites are not detected by microscopy on 2 consecutive occasions.
• Agreement to come back to the hospital on Days 4, 7, 14, 21, 28, 35, 42, 60, 120, and 180.
• A female participant meets eligibility in this study if she is non-pregnant, non-lactating and if she is of: non-childbearing potential defined as: post-menopausal (12 months of spontaneous amenorrhea or \<6 months of spontaneous amenorrhea with serum FSH \>40 mIU/mL), pre-menopausal and has had a hysterectomy, a bilateral oophorectomy (removal of the ovaries), or a bilateral tubal ligation with medical report verification, negative pregnancy test or, child-bearing potential, with a negative pregnancy test at screening, and agrees to comply with one of the following during the treatment stage of the study and for a period of 75 days after stopping study treatment:
• i. Use of oral, implantable, or injectable hormonal contraceptive, either combined or progestogen alone, used in conjunction with barrier method (condom or diaphragm).
• ii. Use of an intrauterine device with a documented failure rate of \<1% per year.
• iii. Double barrier method consisting of condom and diaphragm. iv. Male partner who is sterile prior to the female participant's entry into the study and is the sole sexual partner for that female.
• v. Complete abstinence from intercourse throughout the study and for a period of 75 days after stopping study treatment.
• A male participant meets eligibility in this study if he meets one of the following conditions:
• is sterile prior to participating in the study.
• agrees to the use of a contraceptive method (such as a condom) through the administration of study treatment and for a period of 75 days after stopping study treatment.

You may not qualify if:

• Signs and symptoms of severe/complicated malaria according to the World Health Organization Criteria 2010.
• Mixed Plasmodium infection or Plasmodium mono-infection with any Plasmodium species other than P. vivax.
• Severe vomiting, defined as more than three times in the 24 hours prior to the planned first dose of drug, or severe diarrhea defined as 3 or more watery stools per day.
• Severe malnutrition (defined as the weight-for-height being below -3 standard deviation or less than 70% of median of the NCHS/WHO normalized reference values).
• The presence of a significant medical or psychiatric condition, or any other serious or chronic clinical condition requiring hospitalization, or any other condition that in the opinion of the investigator precludes participation in the study.
• Female participants must not be lactating or pregnant as demonstrated by a negative serum point-of-care pregnancy test pre-dose (the result of the pre-dose assessment must be confirmed negative prior to dosing).
• Employment under the direct supervision of the investigators or study staff.
• Clinically significant alterations to hematologic or clinical chemistry parameters that in the opinion of the investigator precludes participation in the study, including:
• AST/ALT \> 3 x upper limit of normal range (ULN) and total bilirubin is normal.
• AST/ALT \> 2 x ULN and total bilirubin is \>1 and \<2 x ULN and conjugated bilirubin is \> 2x ULN.
• Serum creatinine levels \> 2 x ULN
• Uncorrected electrolyte abnormalities \[\> 3x ULN or LLN\]
• i. Potassium\[hypokalemia\] ii. Magnesium \[hypomagnesemia\] e. Hb level \< 9 g/dL f. Platelet level \< 50,000/mm3
• Clinically significant alterations to cardiac function
• Unstable angina with elevated serum cardiac biomarkers, ECG changes, etc.; those with NSTE-ACS, NSTEMI, STEMI, or definite acute coronary syndrome.

Sponsors & Collaborators

• R. Kiplin Guy: lead
• Global Health Innovative Technology Fund: collaborator
• Congressionally Directed Medical Research Programs: collaborator
• University of Minnesota: collaborator

Study Sites (1)

Asociación Civil Selva Amazónica (ACSA)

Iquitos, Loreto, Peru

Location

Related Publications (3)

• uy, R. K. 2023. "NCT04709692: Efficacy of SJ733 in Adults With Uncomplicated Plasmodium Falciparum or Vivax Malaria." In. https://clinicaltrials.gov/ct2/show/NCT04709692?term=SJ733&draw=2&rank=2.

  BACKGROUND

• Gaur AH, Panetta JC, Smith AM, Dallas RH, Freeman BB 3rd, Stewart TB, Tang L, John E, Branum KC, Patel ND, Ost S, Heine RN, Richardson JL, Hammill JT, Bebrevska L, Gusovsky F, Maki N, Yanagi T, Flynn PM, McCarthy JS, Chalon S, Guy RK. Combining SJ733, an oral ATP4 inhibitor of Plasmodium falciparum, with the pharmacokinetic enhancer cobicistat: An innovative approach in antimalarial drug development. EBioMedicine. 2022 Jun;80:104065. doi: 10.1016/j.ebiom.2022.104065. Epub 2022 May 19.

  PMID: 35598441 BACKGROUND

• Gaur AH, McCarthy JS, Panetta JC, Dallas RH, Woodford J, Tang L, Smith AM, Stewart TB, Branum KC, Freeman BB 3rd, Patel ND, John E, Chalon S, Ost S, Heine RN, Richardson JL, Christensen R, Flynn PM, Van Gessel Y, Mitasev B, Mohrle JJ, Gusovsky F, Bebrevska L, Guy RK. Safety, tolerability, pharmacokinetics, and antimalarial efficacy of a novel Plasmodium falciparum ATP4 inhibitor SJ733: a first-in-human and induced blood-stage malaria phase 1a/b trial. Lancet Infect Dis. 2020 Aug;20(8):964-975. doi: 10.1016/S1473-3099(19)30611-5. Epub 2020 Apr 8.

  PMID: 32275867 BACKGROUND

MeSH Terms

Conditions

Malaria; Malaria, Vivax

Interventions

SJ733; Chloroquine; tafenoquine

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Alejandro L Cuentas,, MD, PhD

  Asociación Civil Selva Amazónica (ACSA), Iquitos, Loreto - Perú

  PRINCIPAL INVESTIGATOR

• Rodney K Guy, PhD

  University of Minnesota

  STUDY DIRECTOR

Central Study Contacts

Rodney K Guy, PhD

CONTACT

901- 481-7251; rguy@umn.edu

Gaurav Shoeran, PhD

CONTACT

gshoeran@umn.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Sponsor and CRO remain blinded (except the unblinded team members). Pharmacist at the site remains unblinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: A blinded, randomized, placebo- and active comparator-controlled Phase 2b Trial of the Combination of SJ733 and Tafenoquine for Radical Cure of P. vivax Malaria. The study is organized with six arms of participants, randomized across all six arms with 1:1:1:1:1:1 ratio.

Study Record Dates

• First Submitted: February 18, 2026
• First Posted: February 24, 2026
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): November 20, 2028
• Study Completion (Estimated): November 20, 2028
• Last Updated: May 28, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

PE (1)