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| Name | Class |
|---|---|
| Global Health Innovative Technology Fund | OTHER |
| Eisai Inc. | INDUSTRY |
| Asociacion Civil Selva Amazonica | OTHER |
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This Phase 2a trial recruits adult patients with uncomplicated P. vivax or P. falciparum blood-stage malaria mono-infection. The study drug SJ733 will be administered to examine its antimalarial efficacy, safety, and tolerability. This study also evaluates whether or not a fixed dose of the pharmacoenhancer cobicistat when given in combination with SJ733 significantly improves drug efficacy.
This is an adaptive open label Phase 2a study to examine the antimalarial efficacy, safety, and tolerability of SJ733 in adult patients with uncomplicated P. vivax or P. falciparum blood-stage malaria monoinfection. SJ733 will be administered orally once every day for three consecutive days, with or without a fixed dose of the pharmacoenhancer cobicistat. The Phase 1 clinical data (completed under a US IND) and PK/PD models suggest that SJ733 is most likely to be curative as a 3-daily-dose pharmacoenhanced therapy, due to its moderately rapid clearance. There will be 1-3 cohorts with each cohort containing two treatment arms, P. falciparum (a) and P. vivax (b). Cohort progression will be managed independently for each treatment arm. Interim analysis will determine whether the data for a given treatment arm meets the success criteria, is inconclusive, or meets the failure criteria. Antimalarial efficacy will be examined over the period of 42 days. Additional aims are to characterize the safety and pharmacokinetics of SJ733. The results of this trial will identify active, well-tolerated doses for investigation in a larger Phase 2b clinical trial.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1 A (cohort 1) | Other | Combination of 600 mg SJ733 with 150 mg Cobicistat administered orally once every day for three consecutive days for patients with P.vivax |
|
| Arm 1 B (cohort 1) | Other | Combination of 600 mg SJ733 with 150 mg Cobicistat administered orally once every day for three consecutive days for patients with P.falciparum |
|
| Arm 2 A (cohort 2) | Other | 600 mg SJ733 administered orally once every day for three consecutive days for patients with P.vivax |
|
| Arm 2 B (cohort 2) | Other | 600 mg SJ733 administered orally once every day for three consecutive days for patients with P.falciparum |
|
| Arm 3 A (cohort 3) | Other | Combination of 300 mg SJ733 with 150 mg Cobicistat administered orally once every day for three consecutive days for patients with P.vivax |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| (+)-SJ000557733 (SJ733) | Drug | Anti-Malarial |
|
| Measure | Description | Time Frame |
|---|---|---|
| Crude Adequate Clinical and Parasitological Response (ACPR) | Crude Adequate Clinical and Parasitological Response (ACPR) defined as the absence of microscopically determined parasitemia (thick smear). | 14 days for each arm |
| Percent of Patients With Treatment Related Adverse Events | Number of and seriousness of treatment related adverse events as defined in Adult Toxicity Tables | 42 days for each arm |
| Percent of Patients With Clinically Significant Abnormal Laboratory Values | Number of and seriousness of clinically significant abnormal laboratory values including changes from baseline in (biochemistry and hematology) | 42 days for each arm |
| Percent of Patients With Clinically Significant Abnormal Vital Signs | Number of and seriousness of clinically significant abnormal vital signs including changes from baseline | 42 days for each arm |
| Percent of Patients With a Decrease in Hemoglobin (HB) > 2 g/dL From Baseline to an Absolute Value of < 5 g/dL | Percent of patients with a decrease in hemoglobin (HB) > 2 g/dL from baseline to an absolute value of < 5 g/dL | 42 days |
| Percent of Patients With an Absolute Neutrophil Count < 1,000/μL After Baseline | Percent of patients with an absolute Neutrophil count < 1,000/μL after baseline | 42 days |
| Percent of Patients Meeting Hy's Law Criteria |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Signs and Symptoms of Uncomplicated Malaria | Number of participants with symptoms (including fever) or physical examination signs related to uncomplicated P. vivax or P. falciparum malaria | 42 days for each arm |
| Parasite Clearance Time |
| Measure | Description | Time Frame |
|---|---|---|
| Crude Adequate Clinical and Parasitological Response (ACPR), PCR Adjusted, at Days 7, 14, 28, 35, and 42 | Crude Adequate Clinical and Parasitological Response (ACPR) as adjusted by quantitative PCR of parasite DNA at Days 7, 14, 28, 35, and 42 | 42 days for each arm |
| Time to Recurrence of Malaria Infection, PCR Adjusted |
Inclusion Criteria:
Male or female, aged 18 to 70 years of age (inclusive) at screening.
Body weight between 45 kg and 90 kg inclusive
Presence of mono-infection of P. falciparum or P. vivax confirmed by:
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 102 hours and/or until malarial parasites are not detected by microscopy on 2 consecutive occasions.
Agreement to come back to the hospital on Days 7, 10 or 11, 14, 17 or 18, 21, 24 or 25, 28, 35, and 42.
Women of child-bearing potential, has 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 90 days after stopping study drug:
Exclusion Criteria:
Signs and symptoms of severe/complicated malaria according to the World Health Organization Criteria 2010 (Attachment 1: Definition of Severe Malaria)
Mixed Plasmodium infection.
Severe vomiting, defined as more than three times in the 24 hours prior to inclusion in the study, 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)
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 patients must not be either 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:
Participation in a clinical study of another investigational small molecule within 30 days or investigational biologic within 90 days prior to study enrollment or planning to begin such participation during the study.
Have received any antimalarial treatment (alone or in combination) in the past containing:
Any medication from the list of prohibited medications.
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| Name | Affiliation | Role |
|---|---|---|
| Alejandro L Cuentas, MD, PhD | Asociación Civil Selva Amazónica (ACSA) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Asociación Civil Selva Amazónica (ACSA) | Iquitos | Loreto | Peru |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25453091 | Background | Jimenez-Diaz MB, Ebert D, Salinas Y, Pradhan A, Lehane AM, Myrand-Lapierre ME, O'Loughlin KG, Shackleford DM, Justino de Almeida M, Carrillo AK, Clark JA, Dennis AS, Diep J, Deng X, Duffy S, Endsley AN, Fedewa G, Guiguemde WA, Gomez MG, Holbrook G, Horst J, Kim CC, Liu J, Lee MC, Matheny A, Martinez MS, Miller G, Rodriguez-Alejandre A, Sanz L, Sigal M, Spillman NJ, Stein PD, Wang Z, Zhu F, Waterson D, Knapp S, Shelat A, Avery VM, Fidock DA, Gamo FJ, Charman SA, Mirsalis JC, Ma H, Ferrer S, Kirk K, Angulo-Barturen I, Kyle DE, DeRisi JL, Floyd DM, Guy RK. (+)-SJ733, a clinical candidate for malaria that acts through ATP4 to induce rapid host-mediated clearance of Plasmodium. Proc Natl Acad Sci U S A. 2014 Dec 16;111(50):E5455-62. doi: 10.1073/pnas.1414221111. Epub 2014 Dec 1. | |
| 32275867 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm 1 B (Cohort 1) | Combination of 600 mg SJ733 with 150 mg Cobicistat administered orally once every day for three consecutive days for patients with P.vivax (+)-SJ000557733 (SJ733): Anti-Malarial |
| FG001 | Arm 2 B (Cohort 2) | 600 mg SJ733 administered orally once every day for three consecutive days for patients with P.vivax (+)-SJ000557733 (SJ733): Anti-Malarial |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm 1 B (Cohort 1) | Combination of 600 mg SJ733 with 150 mg Cobicistat administered orally once every day for three consecutive days for patients with P.vivax (+)-SJ000557733 (SJ733): Anti-Malarial |
| BG001 | Arm 2 B (Cohort 2) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Crude Adequate Clinical and Parasitological Response (ACPR) | Crude Adequate Clinical and Parasitological Response (ACPR) defined as the absence of microscopically determined parasitemia (thick smear). | Only participants eligible for efficacy analysis were analyzed. | Posted | Number | percentage of participants | 14 days for each arm |
|
AE data was collected for the 42 days that a participant was enrolled.
A standard physical examination was performed as per the study schedule and included: general appearance, head and eyes, ears, nose and throat, chest and lungs, cardiovascular, abdomen, neurological, lymphatic, and musculoskeletal. Vital signs, body temperature, and ECGs were taken per the study schedule. Participants were given contact information to self-report AEs between study visits.
Signs and symptoms of malaria were not recorded as adverse events.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm 1 B (Cohort 1) | Combination of 600 mg SJ733 with 150 mg Cobicistat administered orally once every day for three consecutive days for patients with P.vivax (+)-SJ000557733 (SJ733): Anti-Malarial |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Febrile syndrome of probable viral etiology | Infections and infestations | MedDRA v2022AA | Systematic Assessment | MedDRA code: 10072803 SAE due to Hospitalization - prolonged |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Food Poisoning | Gastrointestinal disorders | MedDRA v2022AA | Systematic Assessment | MedDRA: 10016952 Severity: mild |
No participants were recruited into the P. falciparum arm as no participants who tested positive for P. falciparum met monoinfection inclusion criteria due to a decrease in P. falciparum monoinfection in the region.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| R. Kiplin Guy | University of Kentucky | 859-257-5290 | kip.guy@uky.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP_ICF | Yes | Yes | Yes | Study Protocol, Statistical Analysis Plan, and Informed Consent Form | Nov 2, 2020 | May 8, 2023 | Prot_SAP_ICF_001.pdf |
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| ID | Term |
|---|---|
| D016778 | Malaria, Falciparum |
| D016780 | Malaria, Vivax |
| ID | Term |
|---|---|
| D008288 | Malaria |
| D011528 | Protozoan Infections |
| D010272 | Parasitic Diseases |
| D007239 | Infections |
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| ID | Term |
|---|---|
| C000597341 | SJ733 |
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There are 6 treatment arms (three cohorts, each with P. falciparum and P.vivax arms).Cohort progression will be managed independently for each treatment arm. Interim analysis will determine whether the data for each arm meets the success criteria
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| Arm 3 B (cohort 3) |
| Other |
Combination of 300 mg SJ733 with 150 mg Cobicistat administered orally once every day for three consecutive days for patients with P.falciparum |
|
|
Percent of patients meeting Hy's law criteria. Hy's law criteria: (1) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevation of >3× the upper limit of normal (ULN); (2) total bilirubin (TBL) elevation of >2× ULN; (3) absence of initial findings of cholestasis (ie, absence of elevation of alkaline phosphatase [ALP] to >2× ULN); and (4) no other reason can be found to explain the combination of increased ALT and TBL, such as viral hepatitis A through E; other preexisting or acute liver disease; or another drug capable of causing the observed injury. |
| 42 days |
| Percent of Patients With Any ALT or AST ≥ 5 x ULN | Percent of patients with Any ALT or AST ≥ 5 x upper limit of normal (ULN) | 42 days |
| Percent of Patients With a ny AST or ALT ≥ 3 x ULN Together With the Appearance of Fatigue, Nausea, Vomiting, Right Upper Quadrant Pain or Tenderness, Fever, Rash and/or Eosinophilia | Percent of patients with any AST or ALT ≥ 3 x ULN together with the appearance of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash and/or eosinophilia (eosinophil percent or count above the upper limit of normal (ULN)) | 42 days |
| Percent of Patients With Persistent ALT ≥ 3 x ULN for a Period of More Than 4 Weeks. | Percent of patients with persistent ALT ≥ 3 x ULN for a period of more than 4 weeks. | 42 days |
| Percent of Patients With Clinical Signs of Possible Cutaneous Adverse Reactions | Percent of patients with clinical signs of possible cutaneous adverse reactions such as dermatitis, rash, erythematous rash, macular rash, papular rash, maculo-papular rash, pruritic rash, pustular rash, vesicular rash | 42 days |
| Percent of Patients With Clinically Significant Increases in Venous Methemoglobin Levels | Percent of patients with clinically significant increases in venous methemoglobin levels | 42 days |
| Percent of Patients With Significant Changes in ECG Findings | Percent of patients with significant changes in ECG findings, including heart rate, ECG intervals (PR, QTcB, QTcF), conduction changes or abnormalities | 42 days |
Time to parasite clearance as measured by microscopy |
| 42 days for each arm |
| Parasite Reduction Rate | The parasite reduction rate is calculated as the slope of the linear portion of the regression fit of natural log of average parasitemia (per microliter) versus time (in hours). Reported slope is representative of all analyzed participants in each arm. Slope is analyzed during time frame in which there is active reduction of parasitemia by treatment (0->96 h). | 0->96 h, depending upon the time required to reach lower limit of detection |
| Asexual Parasite Clearance Time | Time to clearance of asexual parasites as measured by microscopy including half life of clearance. Clearance time represents the time at which the mean parasitemia has reached the given threshold for the arm/cohort. For PC100, the value represents the time at which all patients have undetectable parasitemia. | 42 days for each arm |
| Percent Change in Asexual Parasites From Baseline | Percentage change of asexual parasites as determined by microscopy, relative to baseline at the specified times. The value represents the average parasitemia in the arm/cohort at the given time (per microliter) versus time (in hours) compared to the average parasitemia at T0. Reported reduction is representative of all analyzed participants in each arm. | 42 days |
| Area Under the Plasma Concentration-time Curve (AUC) | AUC of SJ733 and its metabolite SJ506 will be reported | 11 days for each arm |
| Maximum Plasma Drug Concentration (Cmax) | Cmax of SJ733 and its metabolite SJ506 will be reported | 11 days for each arm |
| Time to Reach Maximum Plasma Concentration (Tmax) | Time to reach maximum plasma concentration (Tmax) of SJ733 will be reported | 11 days for each arm |
| Drug Clearance | Drug clearance of SJ733 and its metabolite SJ506 will be reported | 11 days for each arm |
| Crude Adequate Clinical and Parasitological Response (ACPR) at Days 28, 35, and 42 | Crude Adequate Clinical and Parasitological Response (ACPR) at Days 28, 35, and 42 as measured by microscopy. | 42 days for each arm |
| Time to Recurrence of Malaria Infection | Time to recurrence of either P. vivax or P. falciparum malaria as measured by signs and symptoms or malaria and microscopy | 42 days for each arm |
| Fever Clearance Time | Time from baseline to the first of two consecutive post-dose auxiliary temperature measurements < 37.5 C obtained within an interval of 4 to 24 hours of each other | 42 days for each arm |
Time to recurrence of either P. vivax or P. falciparum malaria as measured by PCR |
| 42 days for each arm |
| 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. |
600 mg SJ733 administered orally once every day for three consecutive days for patients with P.vivax
(+)-SJ000557733 (SJ733): Anti-Malarial
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| Primary | Percent of Patients With Treatment Related Adverse Events | Number of and seriousness of treatment related adverse events as defined in Adult Toxicity Tables | Posted | Count of Participants | Participants | 42 days for each arm |
|
|
|
| Primary | Percent of Patients With Clinically Significant Abnormal Laboratory Values | Number of and seriousness of clinically significant abnormal laboratory values including changes from baseline in (biochemistry and hematology) | Posted | Count of Participants | Participants | 42 days for each arm |
|
|
|
| Primary | Percent of Patients With Clinically Significant Abnormal Vital Signs | Number of and seriousness of clinically significant abnormal vital signs including changes from baseline | Posted | Count of Participants | Participants | 42 days for each arm |
|
|
|
| Primary | Percent of Patients With a Decrease in Hemoglobin (HB) > 2 g/dL From Baseline to an Absolute Value of < 5 g/dL | Percent of patients with a decrease in hemoglobin (HB) > 2 g/dL from baseline to an absolute value of < 5 g/dL | Posted | Count of Participants | Participants | 42 days |
|
|
|
| Primary | Percent of Patients With an Absolute Neutrophil Count < 1,000/μL After Baseline | Percent of patients with an absolute Neutrophil count < 1,000/μL after baseline | Posted | Count of Participants | Participants | 42 days |
|
|
|
| Primary | Percent of Patients Meeting Hy's Law Criteria | Percent of patients meeting Hy's law criteria. Hy's law criteria: (1) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevation of >3× the upper limit of normal (ULN); (2) total bilirubin (TBL) elevation of >2× ULN; (3) absence of initial findings of cholestasis (ie, absence of elevation of alkaline phosphatase [ALP] to >2× ULN); and (4) no other reason can be found to explain the combination of increased ALT and TBL, such as viral hepatitis A through E; other preexisting or acute liver disease; or another drug capable of causing the observed injury. | Posted | Count of Participants | Participants | 42 days |
|
|
|
| Primary | Percent of Patients With Any ALT or AST ≥ 5 x ULN | Percent of patients with Any ALT or AST ≥ 5 x upper limit of normal (ULN) | Posted | Count of Participants | Participants | 42 days |
|
|
|
| Primary | Percent of Patients With a ny AST or ALT ≥ 3 x ULN Together With the Appearance of Fatigue, Nausea, Vomiting, Right Upper Quadrant Pain or Tenderness, Fever, Rash and/or Eosinophilia | Percent of patients with any AST or ALT ≥ 3 x ULN together with the appearance of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash and/or eosinophilia (eosinophil percent or count above the upper limit of normal (ULN)) | Posted | Count of Participants | Participants | 42 days |
|
|
|
| Primary | Percent of Patients With Persistent ALT ≥ 3 x ULN for a Period of More Than 4 Weeks. | Percent of patients with persistent ALT ≥ 3 x ULN for a period of more than 4 weeks. | Posted | Count of Participants | Participants | 42 days |
|
|
|
| Primary | Percent of Patients With Clinical Signs of Possible Cutaneous Adverse Reactions | Percent of patients with clinical signs of possible cutaneous adverse reactions such as dermatitis, rash, erythematous rash, macular rash, papular rash, maculo-papular rash, pruritic rash, pustular rash, vesicular rash | Posted | Count of Participants | Participants | 42 days |
|
|
|
| Primary | Percent of Patients With Clinically Significant Increases in Venous Methemoglobin Levels | Percent of patients with clinically significant increases in venous methemoglobin levels | Posted | Count of Participants | Participants | 42 days |
|
|
|
| Primary | Percent of Patients With Significant Changes in ECG Findings | Percent of patients with significant changes in ECG findings, including heart rate, ECG intervals (PR, QTcB, QTcF), conduction changes or abnormalities | Posted | Count of Participants | Participants | 42 days |
|
|
|
| Secondary | Number of Participants With Signs and Symptoms of Uncomplicated Malaria | Number of participants with symptoms (including fever) or physical examination signs related to uncomplicated P. vivax or P. falciparum malaria | Posted | Count of Participants | Participants | 42 days for each arm |
|
|
|
| Secondary | Parasite Clearance Time | Time to parasite clearance as measured by microscopy | Participants eligible for efficacy measurements were analyzed. | Posted | Mean | 95% Confidence Interval | hours | 42 days for each arm |
|
|
|
| Secondary | Parasite Reduction Rate | The parasite reduction rate is calculated as the slope of the linear portion of the regression fit of natural log of average parasitemia (per microliter) versus time (in hours). Reported slope is representative of all analyzed participants in each arm. Slope is analyzed during time frame in which there is active reduction of parasitemia by treatment (0->96 h). | Participants eligible for efficacy analysis were analyzed | Posted | Mean | 95% Confidence Interval | Ln(parasites/uL)/hour | 0->96 h, depending upon the time required to reach lower limit of detection |
|
|
|
| Secondary | Asexual Parasite Clearance Time | Time to clearance of asexual parasites as measured by microscopy including half life of clearance. Clearance time represents the time at which the mean parasitemia has reached the given threshold for the arm/cohort. For PC100, the value represents the time at which all patients have undetectable parasitemia. | Only participants who were eligible for efficacy analysis were analyzed. | Posted | Mean | Standard Deviation | hours | 42 days for each arm |
|
|
|
| Secondary | Percent Change in Asexual Parasites From Baseline | Percentage change of asexual parasites as determined by microscopy, relative to baseline at the specified times. The value represents the average parasitemia in the arm/cohort at the given time (per microliter) versus time (in hours) compared to the average parasitemia at T0. Reported reduction is representative of all analyzed participants in each arm. | Only data from participants who were eligible for efficacy analysis were analyzed. | Posted | Mean | Standard Deviation | percentage change in parasites | 42 days |
|
|
|
| Secondary | Area Under the Plasma Concentration-time Curve (AUC) | AUC of SJ733 and its metabolite SJ506 will be reported | Arm 2B participant whose condition worsened to severe malaria was not included in analysis due to no data available. | Posted | Median | 95% Confidence Interval | ug*h/L | 11 days for each arm |
|
|
|
| Secondary | Maximum Plasma Drug Concentration (Cmax) | Cmax of SJ733 and its metabolite SJ506 will be reported | Arm 2B participant whose condition worsened to severe malaria was not included in analysis due to no data available. | Posted | Median | 95% Confidence Interval | ng/mL | 11 days for each arm |
|
|
|
| Secondary | Time to Reach Maximum Plasma Concentration (Tmax) | Time to reach maximum plasma concentration (Tmax) of SJ733 will be reported | Arm 2B participant whose condition worsened to severe malaria was not included in analysis as there was no data available. | Posted | Median | 95% Confidence Interval | hours | 11 days for each arm |
|
|
|
| Secondary | Drug Clearance | Drug clearance of SJ733 and its metabolite SJ506 will be reported | Arm 2B participant whose condition progressed to severe malaria was not included in analysis as no PK data was collected. | Posted | Median | 95% Confidence Interval | L/h | 11 days for each arm |
|
|
|
| Secondary | Crude Adequate Clinical and Parasitological Response (ACPR) at Days 28, 35, and 42 | Crude Adequate Clinical and Parasitological Response (ACPR) at Days 28, 35, and 42 as measured by microscopy. | One participant from Arm 2b voluntarily withdrew from the study before the 14 day primary ACPR measurement. That participant's data is not included. One participant from Arm 2b developed severe malaria within hours after the first dose of SJ733. The participant received local treatment of standard of care for severe malaria. That participant's data is not included. | Posted | Number | percentage of participants | 42 days for each arm |
|
|
|
| Secondary | Time to Recurrence of Malaria Infection | Time to recurrence of either P. vivax or P. falciparum malaria as measured by signs and symptoms or malaria and microscopy | Includes participants who were eligible for efficacy analysis. | Posted | Mean | Standard Deviation | days | 42 days for each arm |
|
|
|
| Secondary | Fever Clearance Time | Time from baseline to the first of two consecutive post-dose auxiliary temperature measurements < 37.5 C obtained within an interval of 4 to 24 hours of each other | Analysis includes all eligible participants, including (in arm 2B) one participant who developed severe malaria. | Posted | Mean | 95% Confidence Interval | hours | 42 days for each arm |
|
|
|
| Other Pre-specified | Crude Adequate Clinical and Parasitological Response (ACPR), PCR Adjusted, at Days 7, 14, 28, 35, and 42 | Crude Adequate Clinical and Parasitological Response (ACPR) as adjusted by quantitative PCR of parasite DNA at Days 7, 14, 28, 35, and 42 | Does not include Arm 2B participant who withdrew before day 14 nor Arm 2B participant who developed severe malaria and was treated with local standard of care for severe malaria. | Posted | Number | percentage of participants | 42 days for each arm |
|
|
|
| Other Pre-specified | Time to Recurrence of Malaria Infection, PCR Adjusted | Time to recurrence of either P. vivax or P. falciparum malaria as measured by PCR | Only participants eligible for efficacy analysis were analyzed. | Posted | Mean | Standard Deviation | days | 42 days for each arm |
|
|
|
| 0 |
| 10 |
| 1 |
| 10 |
| 2 |
| 10 |
| EG001 | Arm 2 B (Cohort 2) | 600 mg SJ733 administered orally once every day for three consecutive days for patients with P.vivax (+)-SJ000557733 (SJ733): Anti-Malarial | 0 | 12 | 1 | 12 | 3 | 12 |
|
| Severe Malaria Grade 4 | Infections and infestations | MedDRA v2022AA | Systematic Assessment | MedDRA: 10069722 Severe Malaria Grade 4 |
|
|
| Hepatosplenomegaly | General disorders | MedDRA v2022AA | Systematic Assessment | MedDRA: 10019847 Severity: Mild |
|
| Bilateral nephromegaly | Renal and urinary disorders | MedDRA v2022AA | Systematic Assessment | MedDRA: 10048469 Severity: Mild |
|
| Alkaline Phosphatase Increase | Hepatobiliary disorders | MedDRA v2022AA | Systematic Assessment | MedDRA: 10001675 Severity: Mild |
|
| Acute pharyngitis | Respiratory, thoracic and mediastinal disorders | MedDRA v2022AA | Systematic Assessment | MedDRA:10001002 Severity: Moderate |
|
| Increased Glucose | Endocrine disorders | MedDRA v2022AA | Systematic Assessment | MedDRA: 10018421 Severity: Mild |
|
| Herpetic gingivostomatitis | Infections and infestations | MedDRA v2022AA | Systematic Assessment | MedDRA: 10019996 Severity: Moderate |
|
| D000096724 |
| Mosquito-Borne Diseases |
| D000079426 | Vector Borne Diseases |
| Percent change in asexual parasites from baseline (72h) |
|
| AUC SJ733 at 48 hours |
|
| AUC SJ506 at 48 hours |
|
| AUC SJ733 at 72 hours |
|
| AUC SJ506 at 72 hours |
|
| AUC SJ733 at 96 hours |
|
| AUC SJ506 at 96 hours |
|
| AUC SJ733 at infinity |
|
| AUC SJ506 at infinity |
|
| ACPR day 42 |
|
| ACPR 28 |
|
| ACPR 35 |
|
| ACPR 42 |
|