Healthy
Conditions
Keywords
Healthy Participants, M5717, Malaria, Plasmodium falciparum
Brief summary
The main purpose of this study was to assess the chemoprophylactic activity and dose-exposure-response relationship of single oral dose of M5717 administered after direct intravenous inoculation (DVI) of Plasmodium falciparum sporozoite (PfSPZ) challenge in healthy participants.
Interventions
BIOLOGICALPfSPZ Challenge
Participants received 3200 units of Plasmodium falciparum sporozoites by DVI on Day 1.
DRUGPalcebo
Participants received single oral dose of placebo matched to M5717 capsule on Day 1.
DRUGM5717 30 mg
Participants received 30 mg single oral dose of M5717 capsule on Day 1.
DRUGM5717 60 mg
Participants received 60 mg single oral dose of M5717 capsule on Day 1.
DRUGM5717 80 mg
Participants received 80 mg single oral dose of M5717 capsule on Day 1.
DRUGM5717 100 mg
Participants received 100 mg single oral dose of M5717 capsule on Day 1.
DRUGM5717 200 mg
Participants received 200 mg single oral dose of M5717 capsule on Day 1.
DRUGPlacebo
Participants received single oral dose of placebo matched to M5717 capsule on Day 5.
Sponsors
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Participants who are overtly healthy as determined by medical evaluation, including no clinically significant abnormality identified on physical examination or laboratory evaluation and no active clinically significant disorder, condition, infection or disease that would pose a risk to participant safety or interfere with the study evaluation, procedures or completion * Participants who have a body weight within 50 to 100 kilograms (kg) and body mass index within the range 19.0 to 29.9 kilograms per meter square (kg/m2) (inclusive) * Male participants, during the study intervention period and for at least 120 days after the day of the study intervention dose (covering a full sperm cycle of 90 days starting after 5 half lives of last dose of study intervention: - refrain from donating sperm plus, either - abstain from intercourse with a woman of childbearing potential (WOCBP) or - use a male condom, when having sexual intercourse with a WOCBP, who is not currently pregnant, and advise her to use a highly effective contraceptive method with a failure rate of less than (\<) 1 percent (%) per year, since a condom may break or leak * Female participants who are: - not a WOCBP; - at least 1 year post-menopausal (amenorrhea greater than or equal to \[\>=\] 12 months and follicle-stimulating hormone \[FSH\] \>= 40 milli-international units per milliliter \[mIU/mL\]) at screening; - surgically sterile (bilateral oophorectomy, hysterectomy or bilateral salpingectomy; tubal ligation alone is not sufficient) * Participants who are capable of giving signed informed consent, which includes compliance with the requirements (including mandatory intake of rescue medication to participants who have been administered the investigational Plasmodium falciparum sporozoite challenge) and restrictions listed in the informed consent form (ICF) and this protocol * Other protocol defined inclusion criteria could apply
Exclusion criteria
* Participants with 12-Lead electrocardiogram (ECG) outside normal range (QTcF greater than \[\>\] 450 milli seconds \[ms\], pulse rate \[PR\] \> 215 ms, or QRS \> 120 ms) and deemed clinically relevant by the Investigator * Supine systolic blood pressure \> 140 or \< 90 millimeter of mercury (mmHg), diastolic blood pressure \> 90 or \< 50 mmHg, and pulse rate \> 90 or \< 50 beats per minute (min) at screening and at admission on Day -1 (any abnormal blood pressure or pulse rate results may be repeated once and if the repeat result is within the normal range, it is not considered to have met the exclusion criterion) * Seropositive for human immunodeficiency virus (HIV) I and II antibody or antigen), hepatitis B virus (HBV; hepatitis B surface antigen \[HBsAg\]), or hepatitis C virus (HCV; antibody) tests * Liver function tests above the upper limit of normal (ULN) (\> 3 x ULN) the day before DVI / study intervention administration (Day -1) * History or presence of diagnosed food or known drug allergies (including but not limited to allergy to any of the antimalarial rescue medications to be used in the study), or history of anaphylaxis or other severe allergic reactions * Participant with a whole blood donation or loss of \> 450 mL within 60 days before administration of study drug or unwilling to defer blood donations for 6 months * Other protocol defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Early Liver Stage: Number of Participants Over Time With Positive Parasitemia | Early Liver Stage: From Day 1 up to Day 28 | Number of participants with positive parasitemia defined as first positive quantitative polymerase chain reaction (qPCR) outcome equal or greater than 100 asexual parasites per milliliter (mL) of blood within 28 days of PfSPZ challenge. |
| Late Liver Stage: Number of Participants Over Time With Positive Parasitemia | Late Liver Stage: From Day 5 up to Day 32 | Number of participants with positive parasitemia defined as first positive quantitative polymerase chain reaction (qPCR) outcome equal or greater than 100 asexual parasites per milliliter (mL) of blood within 28 days of PfSPZ challenge. |
| Early Liver Stage: Time to First Positive Parasitemia Based on Quantitative Polymerase Chain Reaction (qPCR) | Early Liver Stage: From Day 1 up to Day 28 | Time to first positive parasitemia was defined as the time (i.e., number of days) from the PfSPZ DVI (i.e., date of DVI PfSPZ) to the first qPCR outcome greater than or equal to (\>=) 100 asexual parasites per milliliter (mL) of blood. |
| Late Liver Stage: Time to First Positive Parasitemia Based on Quantitative Polymerase Chain Reaction (qPCR) | Late Liver Stage: From Day 5 up to Day 32 | Time to first positive parasitemia was defined as the time (i.e., number of days) from the PfSPZ DVI (i.e., date of DVI PfSPZ) to the first qPCR outcome greater than or equal to (\>=) 100 asexual parasites per milliliter (mL) of blood. |
| Early Liver Stage: Number of Participants With Documented Blood Stage Parasite Growth | Early Liver Stage: From Day 1 up to Day 28 | Documented blood stage parasite growth was defined as an increase of qPCR measured asexual parasites per mL compared to the first parasitemia measurement, within 28 days of PfSPZ DVI. |
| Late Liver Stage: Number of Participants With Documented Blood Stage Parasite Growth | Late Liver Stage: From Day 5 up to Day 32 | Documented blood stage parasite growth was defined as an increase of qPCR measured asexual parasites per mL compared to the first parasitemia measurement, within 28 days of PfSPZ DVI. |
| Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | Early Liver Stage: At Day 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 22, 24, 26 and 28 | The malaria clinical score consisted of 14 signs/symptoms frequently associated with malaria and graded using a 4-point scale (absent: 0; mild: 1; moderate: 2; severe: 3) and summed to generate a total malaria clinical score (maximum score possible is 42): headache, myalgia (muscle ache), arthralgia (joint ache), fatigue/lethargy, malaise (general discomfort/uneasiness), chills/shivering/rigors, sweating/hot spells, anorexia, nausea, vomiting, abdominal discomfort, fever, tachycardia and hypotension. The minimum score was 0 (no symptoms) and the maximum score was 42 (maximum symptoms). Total scores are reported here. |
| Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | Late Liver Stage: At Day 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 26, 28, 30 and 32 | The malaria clinical score consisted of 14 signs/symptoms frequently associated with malaria and graded using a 4-point scale (absent: 0; mild: 1; moderate: 2; severe: 3) and summed to generate a total malaria clinical score (maximum score possible is 42): headache, myalgia (muscle ache), arthralgia (joint ache), fatigue/lethargy, malaise (general discomfort/uneasiness), chills/shivering/rigors, sweating/hot spells, anorexia, nausea, vomiting, abdominal discomfort, fever, tachycardia and hypotension. The minimum score was 0 (no symptoms) and the maximum score was 42 (maximum symptoms). Total scores are reported here. |
| Dose Exposure Response Relationship of M5717 Assessed by Logistic Regression Model | From Day 5 up to Day 32 | Exposure efficacy relationship was analyzed using logistic regression model. Different exposure matrices (AUC0-24, AUC0-168, AUC0-inf, C24 and C168) were analyzed using logistic regression model. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Blood Concentration (Cmax) of M5717 | Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 120, 168, 192, 600, and 768 hours post-dose | Cmax was obtained directly from the concentration versus time curve. |
| Blood Concentration at 24 Hours (C24) of M5717 | At 24 hours post-dose | Blood samples for PK analysis of C24 of M5717 was reported. |
| Blood Concentration at 168 Hours (C168) of M5717 | At 168 hours post-dose | C168 is the calculated blood concentration at 168 hours post-dose at which the measured blood concentration is at or above the Lower Limit of quantification (LLQ). |
| Time to Reach Maximum Blood Concentration (Tmax) of M5717 | Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 120, 168, 192, 600, and 768 hours post-dose | Time to reach the maximum blood concentration (Tmax) was obtained directly from the concentration versus time curve. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-related TEAEs | Early Liver Stage: From Day 1 up to Day 33; Late Liver Stage: From Day 1 up to Day 36 | An adverse event (AE) was defined as any untoward medical occurrence in a participant administered with study drug which does not necessarily had a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE was defined as AEs starting or worsening after the first intake of the study drug. TEAEs included both serious TEAEs and non-serious TEAEs. Treatment-related TEAEs: reasonably related to study intervention. |
| Elimination Rate Constant (Lambda z) of M5717 | Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 120, 168, 192, 600, and 768 hours post-dose | Elimination rate constant determined from the terminal slope of the log-transformed concentration curve using linear regression on terminal data points of the curve. |
| Apparent Total Body Clearance From Blood (CL/f) of M5717 | Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 120, 168, 192, 600, and 768 hours post-dose | Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent body clearance of the drug from blood, CL= Dose/AUC0-inf |
| Apparent Volume of Distribution (Vz/F) During the Terminal Phase of M5717 | Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 120, 168, 192, 600, and 768 hours post-dose | The Vz/f was defined as the theoretical volume in which the total amount of required to uniformly distribute to produce the desired plasma concentration. Apparent volume of distribution after oral dose (Vz/F) was influenced by the fraction absorbed. The Vz/f was calculated by dividing the dose with area under the concentration time curve from time zero to infinity multiplied with terminal elimination rate constant Lambda(z). Vz/f=Dose/AUC(0-inf) multiply Lambda(z). |
| Apparent Terminal Half-life (t1/2) of M5717 | Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 120, 168, 192, 600, and 768 hours post-dose | Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by lambda z. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) Based on Severity | Early Liver Stage: From Day 1 up to Day 33; Late Liver Stage: From Day 1 up to Day 36 | Severity of adverse events (AE) were assessed by the investigator per the Qualitative Toxicity Scale. Grade 1= Mild, Grade 2=Moderate, Grade 3=Severe. The number of participants that experienced at least one solicited local TEAE were summarized by grade. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. TEAEs include both Serious TEAEs and non-serious TEAEs. Number of participants with Grade=1, Grade=2 and 3 were reported. |
| Number of Participants With Clinically Significant Change From Baseline in Laboratory Values | Early Liver Stage: From Day 1 up to Day 33; Late Liver Stage: From Day 1 up to Day 36 | Laboratory assessments included hematology, biochemistry, urinalysis, and coagulation. Number of participants with clinically significant changes from baseline in laboratory values which were deemed clinically significant by the investigator were reported. |
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Early Liver Stage: From Day 1 up to Day 33; Late Liver Stage: From Day 1 up to Day 36 | Vital signs included oral body temperature, height, weight, systolic blood pressure, diastolic blood pressure, and pulse rate. Number of participants with clinically significant changes from baseline in Vital signs which were deemed clinically significant by the investigator were reported. |
| Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings | Early Liver Stage: From Day 1 up to Day 33; Late Liver Stage: From Day 1 up to Day 36 | Single 12-lead ECG was obtained as outlined using an ECG machine that automatically calculates the heart rate and measures PR, QRS, and QT intervals. Number of participants with clinically significant changes from baseline in ECG which were deemed clinically significant by the investigator were reported. |
| Area Under the Blood Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M5717 | Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 120, 168, 192, 600, and 768 hours post-dose | AUC0-inf was calculated by combining AUC0-t and AUCextra. AUC extra represents an extrapolated value obtained by Clast/ λz, where Clast is the calculated blood concentration at the last sampling time point at which the measured blood concentration is at or above the Lower Limit of quantification (LLQ) and λz is the apparent terminal rate constant determined by log-linear regression analysis of the measured blood concentrations of the terminal log-linear phase. |
| Area Under the Blood Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-tlast) of M5717 | Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 120, 168, 192, 600, and 768 hours post-dose | Area under the blood concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule. |
| Area Under the Blood Concentration-Time Curve From Time Zero to 24 Hours Post-dose (AUC 0-24) of M5717 | Pre-dose, 0.5, 1, 2, 3, 6, 12 and 24 hours post-dose | AUC from time zero to 24 hours post dose, calculated using the mixed log linear trapezoidal rule (linear up, log down) using the nominal dosing interval. |
| Area Under the Blood Concentration-Time Curve From Time Zero to 168 Hours Post-dose (AUC 0-168) of M5717 | Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 120 and 168 hours post-dose | AUC from time zero to 168 hours post dose. Calculated using the mixed log linear trapezoidal rule (linear up, log down) using the nominal dosing interval. |
Countries
Netherlands
Participant flow
Pre-assignment details
A total of 39 participants (27 participants in early liver stage group and 12 participants in late liver stage group) were enrolled and randomized for treatment at single site in Netherlands.
Participants by arm
| Arm | Count |
|---|---|
| Early Liver Stage: Pooled Placebo Participants received single dose of placebo matched to M5717 capsule on Day 1 after 2 hours of Plasmodium falciparum Sporozoite (PfSPZ) (3200 sporozoites per injection) intravenous (IV) inoculation administration on Day 1. | 6 |
| Early Liver Stage: 30 mg M5717 Participants received single dose of M5717 30 mg capsule on Day 1 after 2 hours of PfSPZ (3200 sporozoites per injection) IV inoculation administration on Day 1. | 3 |
| Early Liver Stage: 60 mg M5717 Participants received single dose of M5717 60 mg capsule on Day 1 after 2 hours of PfSPZ (3200 sporozoites per injection) IV inoculation administration on Day 1. | 6 |
| Early Liver Stage: 80 mg M5717 Participants received single dose of M5717 80 mg capsule on Day 1 after 2 hours of PfSPZ (3200 sporozoites per injection) IV inoculation administration on Day 1. | 6 |
| Early Liver Stage: 100 mg M5717 Participants received single dose of M5717 100 mg capsule on Day 1 after 2 hours of PfSPZ (3200 sporozoites per injection) IV inoculation administration on Day 1. | 3 |
| Early Liver Stage: 200 mg M5717 Participants received single dose of M5717 200 mg capsule on Day 1 after 2 hours of PfSPZ (3200 sporozoites per injection) IV inoculation administration on Day 1. | 3 |
| Late Liver Stage: Pooled Placebo Participants received single dose of placebo matched to M5717 capsule on Day 5 after 96 hours of PfSPZ (3200 sporozoites per injection) IV inoculation administration on Day 1. | 3 |
| Late Liver Stage: 60 mg M5717 Participants received single dose of M5717 60 mg capsule on Day 5 after 96 hours of PfSPZ (3200 sporozoites per injection) IV inoculation administration on Day 1. | 3 |
| Late Liver Stage: 100 mg M5717 Participants received single dose of M5717 100 mg capsule on Day 5 after 96 hours of PfSPZ (3200 sporozoites per injection) IV inoculation administration on Day 1. | 3 |
| Late Liver Stage: 200 mg M5717 Participants received single dose of M5717 200 mg capsule on Day 5 after 96 hours of PfSPZ (3200 sporozoites per injection) IV inoculation administration on Day 1. | 3 |
| Total | 39 |
Baseline characteristics
| Characteristic | Late Liver Stage: 60 mg M5717 | Late Liver Stage: 100 mg M5717 | Late Liver Stage: 200 mg M5717 | Total | Early Liver Stage: Pooled Placebo | Early Liver Stage: 30 mg M5717 | Early Liver Stage: 60 mg M5717 | Early Liver Stage: 80 mg M5717 | Early Liver Stage: 100 mg M5717 | Early Liver Stage: 200 mg M5717 | Late Liver Stage: Pooled Placebo |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 3 Participants | 3 Participants | 39 Participants | 6 Participants | 3 Participants | 6 Participants | 6 Participants | 3 Participants | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 3 Participants | 3 Participants | 38 Participants | 6 Participants | 3 Participants | 5 Participants | 6 Participants | 3 Participants | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 3 Participants | 3 Participants | 35 Participants | 5 Participants | 3 Participants | 6 Participants | 5 Participants | 3 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 1 Participants | 11 Participants | 0 Participants | 0 Participants | 2 Participants | 3 Participants | 0 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Male | 2 Participants | 1 Participants | 2 Participants | 28 Participants | 6 Participants | 3 Participants | 4 Participants | 3 Participants | 3 Participants | 3 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 3 | 0 / 6 | 0 / 6 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 |
| other Total, other adverse events | 5 / 6 | 3 / 3 | 6 / 6 | 6 / 6 | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 2 / 3 | 2 / 3 |
| serious Total, serious adverse events | 0 / 6 | 0 / 3 | 0 / 6 | 0 / 6 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 |
Outcome results
Primary
Dose Exposure Response Relationship of M5717 Assessed by Logistic Regression Model
Exposure efficacy relationship was analyzed using logistic regression model. Different exposure matrices (AUC0-24, AUC0-168, AUC0-inf, C24 and C168) were analyzed using logistic regression model.
Time frame: From Day 5 up to Day 32
Population: PP analysis set included all SAF participants who comply with protocol and meet no criteria that could impact proper evaluation of key objectives of study. This data was analyzed together jointly across cohorts and hence model parameter were based on complete data set as opposed to cohort by cohort.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Early Liver Stage: Pooled Placebo | Dose Exposure Response Relationship of M5717 Assessed by Logistic Regression Model | 1.27 slope |
| Early Liver Stage: 30 mg M5717 | Dose Exposure Response Relationship of M5717 Assessed by Logistic Regression Model | 1.43 slope |
| Early Liver Stage: 60 mg M5717 | Dose Exposure Response Relationship of M5717 Assessed by Logistic Regression Model | 1.44 slope |
| Early Liver Stage: 80 mg M5717 | Dose Exposure Response Relationship of M5717 Assessed by Logistic Regression Model | 0.800 slope |
| Early Liver Stage: 100 mg M5717 | Dose Exposure Response Relationship of M5717 Assessed by Logistic Regression Model | 2.45 slope |
p-value: 0.0028495% CI: [1.85, 10.6]Regression, Logistic
p-value: 0.0036795% CI: [2, 14.8]Regression, Logistic
p-value: 0.013795% CI: [1.9, 23.7]Regression, Logistic
p-value: 0.0034995% CI: [1.47, 4.48]Regression, Logistic
p-value: 0.0059495% CI: [3.19, 129]Regression, Logistic
Primary
Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score
The malaria clinical score consisted of 14 signs/symptoms frequently associated with malaria and graded using a 4-point scale (absent: 0; mild: 1; moderate: 2; severe: 3) and summed to generate a total malaria clinical score (maximum score possible is 42): headache, myalgia (muscle ache), arthralgia (joint ache), fatigue/lethargy, malaise (general discomfort/uneasiness), chills/shivering/rigors, sweating/hot spells, anorexia, nausea, vomiting, abdominal discomfort, fever, tachycardia and hypotension. The minimum score was 0 (no symptoms) and the maximum score was 42 (maximum symptoms). Total scores are reported here.
Time frame: Early Liver Stage: At Day 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 22, 24, 26 and 28
Population: PP analysis set included all SAF participants who comply with the protocol and meet no criteria that could impact the proper evaluation of key objectives of the study. Here, Number analyzed signifies those participants who were evaluable for this outcome at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Early Liver Stage: Pooled Placebo | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 13 | 1.7 score on a Scale | Standard Deviation 1.86 |
| Early Liver Stage: Pooled Placebo | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 15 | 1.5 score on a Scale | Standard Deviation 2.07 |
| Early Liver Stage: Pooled Placebo | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 26 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: Pooled Placebo | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 8 | 0.2 score on a Scale | Standard Deviation 0.41 |
| Early Liver Stage: Pooled Placebo | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 14 | 4.5 score on a Scale | Standard Deviation 3 |
| Early Liver Stage: Pooled Placebo | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 9 | 0.2 score on a Scale | Standard Deviation 0.41 |
| Early Liver Stage: Pooled Placebo | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 6 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: Pooled Placebo | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 12 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: Pooled Placebo | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 17 | 0.5 score on a Scale | Standard Deviation 0.71 |
| Early Liver Stage: Pooled Placebo | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 16 | 2.0 score on a Scale | Standard Deviation 1.41 |
| Early Liver Stage: Pooled Placebo | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 11 | 0.2 score on a Scale | Standard Deviation 0.41 |
| Early Liver Stage: Pooled Placebo | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 28 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: Pooled Placebo | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 10 | 0.3 score on a Scale | Standard Deviation 0.52 |
| Early Liver Stage: Pooled Placebo | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 7 | 0.3 score on a Scale | Standard Deviation 0.52 |
| Early Liver Stage: Pooled Placebo | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 18 | 1.0 score on a Scale | Standard Deviation 1.41 |
| Early Liver Stage: Pooled Placebo | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 22 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 30 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 18 | 2.3 score on a Scale | Standard Deviation 4.04 |
| Early Liver Stage: 30 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 15 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 30 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 16 | 0.3 score on a Scale | Standard Deviation 0.58 |
| Early Liver Stage: 30 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 7 | 0.3 score on a Scale | Standard Deviation 0.58 |
| Early Liver Stage: 30 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 26 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 30 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 8 | 0.3 score on a Scale | Standard Deviation 0.58 |
| Early Liver Stage: 30 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 28 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 30 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 9 | 0.3 score on a Scale | Standard Deviation 0.58 |
| Early Liver Stage: 30 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 22 | 0.7 score on a Scale | Standard Deviation 1.15 |
| Early Liver Stage: 30 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 10 | 0.3 score on a Scale | Standard Deviation 0.58 |
| Early Liver Stage: 30 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 20 | 1.0 score on a Scale | Standard Deviation 1.73 |
| Early Liver Stage: 30 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 11 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 30 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 19 | 0.7 score on a Scale | Standard Deviation 1.15 |
| Early Liver Stage: 30 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 12 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 30 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 14 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 30 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 13 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 30 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 6 | 0.3 score on a Scale | Standard Deviation 0.58 |
| Early Liver Stage: 30 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 17 | 2.0 score on a Scale | Standard Deviation 3.46 |
| Early Liver Stage: 60 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 15 | 0.2 score on a Scale | Standard Deviation 0.41 |
| Early Liver Stage: 60 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 20 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 60 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 19 | 0.3 score on a Scale | Standard Deviation 0.52 |
| Early Liver Stage: 60 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 28 | 0.2 score on a Scale | Standard Deviation 0.41 |
| Early Liver Stage: 60 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 14 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 60 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 11 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 60 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 16 | 0.3 score on a Scale | Standard Deviation 0.52 |
| Early Liver Stage: 60 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 18 | 0.3 score on a Scale | Standard Deviation 0.52 |
| Early Liver Stage: 60 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 24 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 60 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 22 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 60 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 8 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 60 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 6 | 0.2 score on a Scale | Standard Deviation 0.41 |
| Early Liver Stage: 60 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 9 | 0.2 score on a Scale | Standard Deviation 0.41 |
| Early Liver Stage: 60 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 17 | 0.3 score on a Scale | Standard Deviation 0.52 |
| Early Liver Stage: 60 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 13 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 60 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 7 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 60 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 26 | 0.2 score on a Scale | Standard Deviation 0.41 |
| Early Liver Stage: 60 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 12 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 60 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 10 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 80 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 14 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 80 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 11 | 0.2 score on a Scale | Standard Deviation 0.41 |
| Early Liver Stage: 80 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 6 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 80 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 7 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 80 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 8 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 80 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 9 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 80 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 10 | 0.3 score on a Scale | Standard Deviation 0.52 |
| Early Liver Stage: 80 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 12 | 0.2 score on a Scale | Standard Deviation 0.41 |
| Early Liver Stage: 80 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 13 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 80 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 15 | 0.2 score on a Scale | Standard Deviation 0.41 |
| Early Liver Stage: 80 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 16 | 0.2 score on a Scale | Standard Deviation 0.41 |
| Early Liver Stage: 80 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 17 | 0.2 score on a Scale | Standard Deviation 0.41 |
| Early Liver Stage: 80 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 18 | 0.2 score on a Scale | Standard Deviation 0.41 |
| Early Liver Stage: 80 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 19 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 80 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 20 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 80 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 22 | 0.2 score on a Scale | Standard Deviation 0.41 |
| Early Liver Stage: 80 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 24 | 0.2 score on a Scale | Standard Deviation 0.41 |
| Early Liver Stage: 80 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 26 | 0.2 score on a Scale | Standard Deviation 0.41 |
| Early Liver Stage: 80 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 28 | 0.2 score on a Scale | Standard Deviation 0.41 |
| Early Liver Stage: 100 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 6 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 100 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 22 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 100 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 19 | 0.3 score on a Scale | Standard Deviation 0.58 |
| Early Liver Stage: 100 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 8 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 100 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 18 | 0.3 score on a Scale | Standard Deviation 0.58 |
| Early Liver Stage: 100 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 24 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 100 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 10 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 100 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 14 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 100 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 7 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 100 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 20 | 0.3 score on a Scale | Standard Deviation 0.58 |
| Early Liver Stage: 100 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 13 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 100 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 15 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 100 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 11 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 100 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 28 | 0.3 score on a Scale | Standard Deviation 0.58 |
| Early Liver Stage: 100 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 16 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 100 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 9 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 100 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 12 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 100 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 26 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 100 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 17 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 200 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 12 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 200 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 11 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 200 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 26 | 0.3 score on a Scale | Standard Deviation 0.58 |
| Early Liver Stage: 200 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 18 | 0.3 score on a Scale | Standard Deviation 0.58 |
| Early Liver Stage: 200 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 10 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 200 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 19 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 200 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 20 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 200 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 9 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 200 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 8 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 200 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 17 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 200 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 22 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 200 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 28 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 200 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 24 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 200 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 7 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 200 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 6 | 0.1 score on a Scale | Standard Deviation 0.3 |
| Early Liver Stage: 200 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 15 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 200 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 14 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 200 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 16 | 0.0 score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 200 mg M5717 | Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 13 | 0.0 score on a Scale | Standard Deviation 0 |
Primary
Early Liver Stage: Number of Participants Over Time With Positive Parasitemia
Number of participants with positive parasitemia defined as first positive quantitative polymerase chain reaction (qPCR) outcome equal or greater than 100 asexual parasites per milliliter (mL) of blood within 28 days of PfSPZ challenge.
Time frame: Early Liver Stage: From Day 1 up to Day 28
Population: Per-protocol (PP) analysis set included all SAF participants who comply with the protocol and meet no criteria that could impact the proper evaluation of key objectives of the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Early Liver Stage: Pooled Placebo | Early Liver Stage: Number of Participants Over Time With Positive Parasitemia | 6 Participants |
| Early Liver Stage: 30 mg M5717 | Early Liver Stage: Number of Participants Over Time With Positive Parasitemia | 3 Participants |
| Early Liver Stage: 60 mg M5717 | Early Liver Stage: Number of Participants Over Time With Positive Parasitemia | 2 Participants |
| Early Liver Stage: 80 mg M5717 | Early Liver Stage: Number of Participants Over Time With Positive Parasitemia | 1 Participants |
| Early Liver Stage: 100 mg M5717 | Early Liver Stage: Number of Participants Over Time With Positive Parasitemia | 0 Participants |
| Early Liver Stage: 200 mg M5717 | Early Liver Stage: Number of Participants Over Time With Positive Parasitemia | 0 Participants |
Primary
Early Liver Stage: Number of Participants With Documented Blood Stage Parasite Growth
Documented blood stage parasite growth was defined as an increase of qPCR measured asexual parasites per mL compared to the first parasitemia measurement, within 28 days of PfSPZ DVI.
Time frame: Early Liver Stage: From Day 1 up to Day 28
Population: PP analysis set included all SAF participants who comply with the protocol and meet no criteria that could impact the proper evaluation of key objectives of the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Early Liver Stage: Pooled Placebo | Early Liver Stage: Number of Participants With Documented Blood Stage Parasite Growth | 5 Participants |
| Early Liver Stage: 30 mg M5717 | Early Liver Stage: Number of Participants With Documented Blood Stage Parasite Growth | 2 Participants |
| Early Liver Stage: 60 mg M5717 | Early Liver Stage: Number of Participants With Documented Blood Stage Parasite Growth | 2 Participants |
| Early Liver Stage: 80 mg M5717 | Early Liver Stage: Number of Participants With Documented Blood Stage Parasite Growth | 1 Participants |
| Early Liver Stage: 100 mg M5717 | Early Liver Stage: Number of Participants With Documented Blood Stage Parasite Growth | 0 Participants |
| Early Liver Stage: 200 mg M5717 | Early Liver Stage: Number of Participants With Documented Blood Stage Parasite Growth | 0 Participants |
Primary
Early Liver Stage: Time to First Positive Parasitemia Based on Quantitative Polymerase Chain Reaction (qPCR)
Time to first positive parasitemia was defined as the time (i.e., number of days) from the PfSPZ DVI (i.e., date of DVI PfSPZ) to the first qPCR outcome greater than or equal to (\>=) 100 asexual parasites per milliliter (mL) of blood.
Time frame: Early Liver Stage: From Day 1 up to Day 28
Population: PP analysis set included all SAF participants who comply with the protocol and meet no criteria that could impact the proper evaluation of key objectives of the study. Here, Overall Number of Participants Analyzed signifies those participants who had positive parasitemia.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Early Liver Stage: Pooled Placebo | Early Liver Stage: Time to First Positive Parasitemia Based on Quantitative Polymerase Chain Reaction (qPCR) | 10.0 Days |
| Early Liver Stage: 30 mg M5717 | Early Liver Stage: Time to First Positive Parasitemia Based on Quantitative Polymerase Chain Reaction (qPCR) | 15.0 Days |
| Early Liver Stage: 60 mg M5717 | Early Liver Stage: Time to First Positive Parasitemia Based on Quantitative Polymerase Chain Reaction (qPCR) | 22.0 Days |
| Early Liver Stage: 80 mg M5717 | Early Liver Stage: Time to First Positive Parasitemia Based on Quantitative Polymerase Chain Reaction (qPCR) | 24.0 Days |
Primary
Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score
The malaria clinical score consisted of 14 signs/symptoms frequently associated with malaria and graded using a 4-point scale (absent: 0; mild: 1; moderate: 2; severe: 3) and summed to generate a total malaria clinical score (maximum score possible is 42): headache, myalgia (muscle ache), arthralgia (joint ache), fatigue/lethargy, malaise (general discomfort/uneasiness), chills/shivering/rigors, sweating/hot spells, anorexia, nausea, vomiting, abdominal discomfort, fever, tachycardia and hypotension. The minimum score was 0 (no symptoms) and the maximum score was 42 (maximum symptoms). Total scores are reported here.
Time frame: Late Liver Stage: At Day 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 26, 28, 30 and 32
Population: PP analysis set included all SAF participants who comply with the protocol and meet no criteria that could impact the proper evaluation of key objectives of the study. Here, Number analyzed signifies those participants who were evaluable for this outcome at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Early Liver Stage: Pooled Placebo | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 14 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: Pooled Placebo | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 13 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: Pooled Placebo | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 10 | 0.3 Score on a Scale | Standard Deviation 0.58 |
| Early Liver Stage: Pooled Placebo | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 32 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: Pooled Placebo | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 17 | 1.0 Score on a Scale | — |
| Early Liver Stage: Pooled Placebo | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 12 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: Pooled Placebo | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 8 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: Pooled Placebo | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 26 | 0.3 Score on a Scale | Standard Deviation 0.58 |
| Early Liver Stage: Pooled Placebo | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 6 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: Pooled Placebo | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 19 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: Pooled Placebo | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 16 | 1.5 Score on a Scale | Standard Deviation 2.12 |
| Early Liver Stage: Pooled Placebo | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 15 | 1.5 Score on a Scale | Standard Deviation 2.12 |
| Early Liver Stage: Pooled Placebo | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 9 | 0.3 Score on a Scale | Standard Deviation 0.58 |
| Early Liver Stage: Pooled Placebo | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 11 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: Pooled Placebo | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 7 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: Pooled Placebo | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 30 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 30 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 22 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 30 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 23 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 30 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 9 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 30 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 24 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 30 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 26 | 0.3 Score on a Scale | Standard Deviation 0.58 |
| Early Liver Stage: 30 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 28 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 30 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 30 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 30 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 32 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 30 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 10 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 30 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 6 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 30 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 12 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 30 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 13 | 0.3 Score on a Scale | Standard Deviation 0.58 |
| Early Liver Stage: 30 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 14 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 30 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 7 | 0.3 Score on a Scale | Standard Deviation 0.58 |
| Early Liver Stage: 30 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 15 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 30 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 16 | 0.3 Score on a Scale | Standard Deviation 0.58 |
| Early Liver Stage: 30 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 11 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 30 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 17 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 30 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 18 | 0.3 Score on a Scale | Standard Deviation 0.58 |
| Early Liver Stage: 30 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 8 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 30 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 19 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 30 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 20 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 30 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 21 | 0.3 Score on a Scale | Standard Deviation 0.58 |
| Early Liver Stage: 60 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 9 | 0.3 Score on a Scale | Standard Deviation 0.58 |
| Early Liver Stage: 60 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 23 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 60 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 15 | 0.3 Score on a Scale | Standard Deviation 0.58 |
| Early Liver Stage: 60 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 7 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 60 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 26 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 60 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 22 | 0.3 Score on a Scale | Standard Deviation 0.58 |
| Early Liver Stage: 60 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 16 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 60 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 19 | 0.3 Score on a Scale | Standard Deviation 0.58 |
| Early Liver Stage: 60 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 24 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 60 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 10 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 60 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 11 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 60 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 8 | 0.3 Score on a Scale | Standard Deviation 0.58 |
| Early Liver Stage: 60 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 32 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 60 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 17 | 0.3 Score on a Scale | Standard Deviation 0.58 |
| Early Liver Stage: 60 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 12 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 60 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 6 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 60 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 30 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 60 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 21 | 0.3 Score on a Scale | Standard Deviation 0.58 |
| Early Liver Stage: 60 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 13 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 60 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 28 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 60 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 18 | 0.3 Score on a Scale | Standard Deviation 0.58 |
| Early Liver Stage: 60 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 14 | 0.3 Score on a Scale | Standard Deviation 0.58 |
| Early Liver Stage: 60 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 20 | 0.3 Score on a Scale | Standard Deviation 0.58 |
| Early Liver Stage: 80 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 32 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 80 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 17 | 0.7 Score on a Scale | Standard Deviation 1.15 |
| Early Liver Stage: 80 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 20 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 80 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 24 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 80 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 6 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 80 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 7 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 80 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 8 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 80 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 9 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 80 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 10 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 80 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 11 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 80 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 12 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 80 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 13 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 80 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 14 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 80 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 15 | 0.3 Score on a Scale | Standard Deviation 0.58 |
| Early Liver Stage: 80 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 16 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 80 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 18 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 80 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 19 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 80 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 21 | 0.3 Score on a Scale | Standard Deviation 0.58 |
| Early Liver Stage: 80 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 22 | 0.3 Score on a Scale | Standard Deviation 0.58 |
| Early Liver Stage: 80 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 23 | 0.3 Score on a Scale | Standard Deviation 0.58 |
| Early Liver Stage: 80 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 26 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 80 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 28 | 0.0 Score on a Scale | Standard Deviation 0 |
| Early Liver Stage: 80 mg M5717 | Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score | At Day 30 | 0.00 Score on a Scale | Standard Deviation 0 |
Primary
Late Liver Stage: Number of Participants Over Time With Positive Parasitemia
Number of participants with positive parasitemia defined as first positive quantitative polymerase chain reaction (qPCR) outcome equal or greater than 100 asexual parasites per milliliter (mL) of blood within 28 days of PfSPZ challenge.
Time frame: Late Liver Stage: From Day 5 up to Day 32
Population: PP analysis set included all SAF participants who comply with the protocol and meet no criteria that could impact the proper evaluation of key objectives of the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Early Liver Stage: Pooled Placebo | Late Liver Stage: Number of Participants Over Time With Positive Parasitemia | 3 Participants |
| Early Liver Stage: 30 mg M5717 | Late Liver Stage: Number of Participants Over Time With Positive Parasitemia | 0 Participants |
| Early Liver Stage: 60 mg M5717 | Late Liver Stage: Number of Participants Over Time With Positive Parasitemia | 0 Participants |
| Early Liver Stage: 80 mg M5717 | Late Liver Stage: Number of Participants Over Time With Positive Parasitemia | 0 Participants |
Primary
Late Liver Stage: Number of Participants With Documented Blood Stage Parasite Growth
Documented blood stage parasite growth was defined as an increase of qPCR measured asexual parasites per mL compared to the first parasitemia measurement, within 28 days of PfSPZ DVI.
Time frame: Late Liver Stage: From Day 5 up to Day 32
Population: PP analysis set included all SAF participants who comply with the protocol and meet no criteria that could impact the proper evaluation of key objectives of the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Early Liver Stage: Pooled Placebo | Late Liver Stage: Number of Participants With Documented Blood Stage Parasite Growth | 3 Participants |
| Early Liver Stage: 30 mg M5717 | Late Liver Stage: Number of Participants With Documented Blood Stage Parasite Growth | 0 Participants |
| Early Liver Stage: 60 mg M5717 | Late Liver Stage: Number of Participants With Documented Blood Stage Parasite Growth | 0 Participants |
| Early Liver Stage: 80 mg M5717 | Late Liver Stage: Number of Participants With Documented Blood Stage Parasite Growth | 0 Participants |
Primary
Late Liver Stage: Time to First Positive Parasitemia Based on Quantitative Polymerase Chain Reaction (qPCR)
Time to first positive parasitemia was defined as the time (i.e., number of days) from the PfSPZ DVI (i.e., date of DVI PfSPZ) to the first qPCR outcome greater than or equal to (\>=) 100 asexual parasites per milliliter (mL) of blood.
Time frame: Late Liver Stage: From Day 5 up to Day 32
Population: PP analysis set included all SAF participants who comply with the protocol and meet no criteria that could impact the proper evaluation of key objectives of the study. Here, Overall Number of Participants Analyzed signifies those participants who had positive parasitemia.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Early Liver Stage: Pooled Placebo | Late Liver Stage: Time to First Positive Parasitemia Based on Quantitative Polymerase Chain Reaction (qPCR) | 10.0 Days |
Secondary
Apparent Terminal Half-life (t1/2) of M5717
Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by lambda z.
Time frame: Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 120, 168, 192, 600, and 768 hours post-dose
Population: PK analysis set included all participants, who received 1 dose of M5717, had no clinically important protocol deviations/important events affecting PK, \& provide at least 1 measurable post-dose concentration. Data was not available for 'Early liver stage: 30 mg M5717' arm as no participants were considered evaluable because of limited number of samples collected to characterize the elimination rate constant (lambda z) needed for calculation of t1/2.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Early Liver Stage: 30 mg M5717 | Apparent Terminal Half-life (t1/2) of M5717 | 121 Hours |
| Early Liver Stage: 60 mg M5717 | Apparent Terminal Half-life (t1/2) of M5717 | 121 Hours |
| Early Liver Stage: 80 mg M5717 | Apparent Terminal Half-life (t1/2) of M5717 | 66.9 Hours |
| Early Liver Stage: 100 mg M5717 | Apparent Terminal Half-life (t1/2) of M5717 | 494 Hours |
| Early Liver Stage: 200 mg M5717 | Apparent Terminal Half-life (t1/2) of M5717 | 94.1 Hours |
| Late Liver Stage: Pooled Placebo | Apparent Terminal Half-life (t1/2) of M5717 | 95.4 Hours |
| Late Liver Stage: 60 mg M5717 | Apparent Terminal Half-life (t1/2) of M5717 | 136 Hours |
Secondary
Apparent Total Body Clearance From Blood (CL/f) of M5717
Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent body clearance of the drug from blood, CL= Dose/AUC0-inf
Time frame: Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 120, 168, 192, 600, and 768 hours post-dose
Population: PK analysis set included all participants, who received 1 dose of M5717, had no clinically important protocol deviations/important events affecting PK, \& provide at least 1 measurable post-dose concentration. Data was not available for 'Early liver stage: 30 mg M5717' arm as no participants were considered evaluable because of limited number of samples collected to characterize the elimination rate constant (lambda z) needed for calculation of CL/f.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Early Liver Stage: 30 mg M5717 | Apparent Total Body Clearance From Blood (CL/f) of M5717 | 46.9 Liter per Hours (L/h) | Geometric Coefficient of Variation 31.81 |
| Early Liver Stage: 60 mg M5717 | Apparent Total Body Clearance From Blood (CL/f) of M5717 | 40.3 Liter per Hours (L/h) | Geometric Coefficient of Variation 25.24 |
| Early Liver Stage: 80 mg M5717 | Apparent Total Body Clearance From Blood (CL/f) of M5717 | 52.9 Liter per Hours (L/h) | Geometric Coefficient of Variation 12.52 |
| Early Liver Stage: 100 mg M5717 | Apparent Total Body Clearance From Blood (CL/f) of M5717 | 20.3 Liter per Hours (L/h) | Geometric Coefficient of Variation 37.44 |
| Early Liver Stage: 200 mg M5717 | Apparent Total Body Clearance From Blood (CL/f) of M5717 | 54.8 Liter per Hours (L/h) | Geometric Coefficient of Variation 71.03 |
| Late Liver Stage: Pooled Placebo | Apparent Total Body Clearance From Blood (CL/f) of M5717 | 43.0 Liter per Hours (L/h) | Geometric Coefficient of Variation 4.7 |
| Late Liver Stage: 60 mg M5717 | Apparent Total Body Clearance From Blood (CL/f) of M5717 | 41.4 Liter per Hours (L/h) | Geometric Coefficient of Variation 53.73 |
Secondary
Apparent Volume of Distribution (Vz/F) During the Terminal Phase of M5717
The Vz/f was defined as the theoretical volume in which the total amount of required to uniformly distribute to produce the desired plasma concentration. Apparent volume of distribution after oral dose (Vz/F) was influenced by the fraction absorbed. The Vz/f was calculated by dividing the dose with area under the concentration time curve from time zero to infinity multiplied with terminal elimination rate constant Lambda(z). Vz/f=Dose/AUC(0-inf) multiply Lambda(z).
Time frame: Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 120, 168, 192, 600, and 768 hours post-dose
Population: PK analysis set included all participants, who received 1 dose of M5717, had no clinically important protocol deviations/important events affecting PK, \& provide at least 1 measurable post-dose concentration. Data was not available for 'Early liver stage: 30 mg M5717' arm as no participants were considered evaluable because of limited number of samples collected to characterize the elimination rate constant (lambda z) needed for calculation of Vz/F.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Early Liver Stage: 30 mg M5717 | Apparent Volume of Distribution (Vz/F) During the Terminal Phase of M5717 | 7850 Liter | Geometric Coefficient of Variation 42.71 |
| Early Liver Stage: 60 mg M5717 | Apparent Volume of Distribution (Vz/F) During the Terminal Phase of M5717 | 7600 Liter | Geometric Coefficient of Variation 10.87 |
| Early Liver Stage: 80 mg M5717 | Apparent Volume of Distribution (Vz/F) During the Terminal Phase of M5717 | 5980 Liter | Geometric Coefficient of Variation 15.57 |
| Early Liver Stage: 100 mg M5717 | Apparent Volume of Distribution (Vz/F) During the Terminal Phase of M5717 | 11200 Liter | Geometric Coefficient of Variation 60.47 |
| Early Liver Stage: 200 mg M5717 | Apparent Volume of Distribution (Vz/F) During the Terminal Phase of M5717 | 8130 Liter | Geometric Coefficient of Variation 35.29 |
| Late Liver Stage: Pooled Placebo | Apparent Volume of Distribution (Vz/F) During the Terminal Phase of M5717 | 5490 Liter | Geometric Coefficient of Variation 15.71 |
| Late Liver Stage: 60 mg M5717 | Apparent Volume of Distribution (Vz/F) During the Terminal Phase of M5717 | 27.59 Liter | Geometric Coefficient of Variation 8340 |
Secondary
Area Under the Blood Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M5717
AUC0-inf was calculated by combining AUC0-t and AUCextra. AUC extra represents an extrapolated value obtained by Clast/ λz, where Clast is the calculated blood concentration at the last sampling time point at which the measured blood concentration is at or above the Lower Limit of quantification (LLQ) and λz is the apparent terminal rate constant determined by log-linear regression analysis of the measured blood concentrations of the terminal log-linear phase.
Time frame: Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 120, 168, 192, 600, and 768 hours post-dose
Population: PK analysis set included all participants, who received 1 dose of M5717, had no clinically important protocol deviations/important events affecting PK, \& provide at least 1 measurable post-dose concentration. Data was not available for 'Early liver stage: 30 mg M5717' arm as no participants were considered evaluable because of limited number of samples collected to characterize the elimination rate constant (lambda z) needed for calculation of AUC0-inf.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Early Liver Stage: 30 mg M5717 | Area Under the Blood Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M5717 | 1280 hour*nanogram per milliliter(hour*ng/mL) | Geometric Coefficient of Variation 31.81 |
| Early Liver Stage: 60 mg M5717 | Area Under the Blood Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M5717 | 1990 hour*nanogram per milliliter(hour*ng/mL) | Geometric Coefficient of Variation 25.24 |
| Early Liver Stage: 80 mg M5717 | Area Under the Blood Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M5717 | 1890 hour*nanogram per milliliter(hour*ng/mL) | Geometric Coefficient of Variation 12.52 |
| Early Liver Stage: 100 mg M5717 | Area Under the Blood Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M5717 | 9840 hour*nanogram per milliliter(hour*ng/mL) | Geometric Coefficient of Variation 37.44 |
| Early Liver Stage: 200 mg M5717 | Area Under the Blood Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M5717 | 1100 hour*nanogram per milliliter(hour*ng/mL) | Geometric Coefficient of Variation 71.03 |
| Late Liver Stage: Pooled Placebo | Area Under the Blood Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M5717 | 2330 hour*nanogram per milliliter(hour*ng/mL) | Geometric Coefficient of Variation 4.7 |
| Late Liver Stage: 60 mg M5717 | Area Under the Blood Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M5717 | 4830 hour*nanogram per milliliter(hour*ng/mL) | Geometric Coefficient of Variation 53.73 |
Secondary
Area Under the Blood Concentration-Time Curve From Time Zero to 168 Hours Post-dose (AUC 0-168) of M5717
AUC from time zero to 168 hours post dose. Calculated using the mixed log linear trapezoidal rule (linear up, log down) using the nominal dosing interval.
Time frame: Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 120 and 168 hours post-dose
Population: Pharmacokinetic analysis set included all participants, who received one dose of M5717, have no clinically important protocol deviations or important events affecting PK, and provide at least one measurable post-dose concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Early Liver Stage: Pooled Placebo | Area Under the Blood Concentration-Time Curve From Time Zero to 168 Hours Post-dose (AUC 0-168) of M5717 | 50.4 h*ng/mL | Geometric Coefficient of Variation 2325.31 |
| Early Liver Stage: 30 mg M5717 | Area Under the Blood Concentration-Time Curve From Time Zero to 168 Hours Post-dose (AUC 0-168) of M5717 | 805 h*ng/mL | Geometric Coefficient of Variation 35.22 |
| Early Liver Stage: 60 mg M5717 | Area Under the Blood Concentration-Time Curve From Time Zero to 168 Hours Post-dose (AUC 0-168) of M5717 | 1190 h*ng/mL | Geometric Coefficient of Variation 14.35 |
| Early Liver Stage: 80 mg M5717 | Area Under the Blood Concentration-Time Curve From Time Zero to 168 Hours Post-dose (AUC 0-168) of M5717 | 1390 h*ng/mL | Geometric Coefficient of Variation 5.34 |
| Early Liver Stage: 100 mg M5717 | Area Under the Blood Concentration-Time Curve From Time Zero to 168 Hours Post-dose (AUC 0-168) of M5717 | 3680 h*ng/mL | Geometric Coefficient of Variation 29.33 |
| Early Liver Stage: 200 mg M5717 | Area Under the Blood Concentration-Time Curve From Time Zero to 168 Hours Post-dose (AUC 0-168) of M5717 | 692 h*ng/mL | Geometric Coefficient of Variation 53.24 |
| Late Liver Stage: Pooled Placebo | Area Under the Blood Concentration-Time Curve From Time Zero to 168 Hours Post-dose (AUC 0-168) of M5717 | 1710 h*ng/mL | Geometric Coefficient of Variation 8.67 |
| Late Liver Stage: 60 mg M5717 | Area Under the Blood Concentration-Time Curve From Time Zero to 168 Hours Post-dose (AUC 0-168) of M5717 | 3190 h*ng/mL | Geometric Coefficient of Variation 43.4 |
Secondary
Area Under the Blood Concentration-Time Curve From Time Zero to 24 Hours Post-dose (AUC 0-24) of M5717
AUC from time zero to 24 hours post dose, calculated using the mixed log linear trapezoidal rule (linear up, log down) using the nominal dosing interval.
Time frame: Pre-dose, 0.5, 1, 2, 3, 6, 12 and 24 hours post-dose
Population: Pharmacokinetic analysis set included all participants, who received one dose of M5717, have no clinically important protocol deviations or important events affecting PK, and provide at least one measurable post-dose concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Early Liver Stage: Pooled Placebo | Area Under the Blood Concentration-Time Curve From Time Zero to 24 Hours Post-dose (AUC 0-24) of M5717 | 25.8 h*ng/mL | Geometric Coefficient of Variation 639.59 |
| Early Liver Stage: 30 mg M5717 | Area Under the Blood Concentration-Time Curve From Time Zero to 24 Hours Post-dose (AUC 0-24) of M5717 | 198 h*ng/mL | Geometric Coefficient of Variation 40.21 |
| Early Liver Stage: 60 mg M5717 | Area Under the Blood Concentration-Time Curve From Time Zero to 24 Hours Post-dose (AUC 0-24) of M5717 | 280 h*ng/mL | Geometric Coefficient of Variation 18.23 |
| Early Liver Stage: 80 mg M5717 | Area Under the Blood Concentration-Time Curve From Time Zero to 24 Hours Post-dose (AUC 0-24) of M5717 | 290 h*ng/mL | Geometric Coefficient of Variation 39.8 |
| Early Liver Stage: 100 mg M5717 | Area Under the Blood Concentration-Time Curve From Time Zero to 24 Hours Post-dose (AUC 0-24) of M5717 | 975 h*ng/mL | Geometric Coefficient of Variation 33.02 |
| Early Liver Stage: 200 mg M5717 | Area Under the Blood Concentration-Time Curve From Time Zero to 24 Hours Post-dose (AUC 0-24) of M5717 | 160 h*ng/mL | Geometric Coefficient of Variation 44.63 |
| Late Liver Stage: Pooled Placebo | Area Under the Blood Concentration-Time Curve From Time Zero to 24 Hours Post-dose (AUC 0-24) of M5717 | 445 h*ng/mL | Geometric Coefficient of Variation 8.6 |
| Late Liver Stage: 60 mg M5717 | Area Under the Blood Concentration-Time Curve From Time Zero to 24 Hours Post-dose (AUC 0-24) of M5717 | 1020 h*ng/mL | Geometric Coefficient of Variation 45.85 |
Secondary
Area Under the Blood Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-tlast) of M5717
Area under the blood concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule.
Time frame: Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 120, 168, 192, 600, and 768 hours post-dose
Population: Pharmacokinetic analysis set included all participants, who received one dose of M5717, have no clinically important protocol deviations or important events affecting PK, and provide at least one measurable post-dose concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Early Liver Stage: Pooled Placebo | Area Under the Blood Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-tlast) of M5717 | 21.9 hour*ng/mL | Geometric Coefficient of Variation 1160.32 |
| Early Liver Stage: 30 mg M5717 | Area Under the Blood Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-tlast) of M5717 | 852 hour*ng/mL | Geometric Coefficient of Variation 36.35 |
| Early Liver Stage: 60 mg M5717 | Area Under the Blood Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-tlast) of M5717 | 1270 hour*ng/mL | Geometric Coefficient of Variation 14.08 |
| Early Liver Stage: 80 mg M5717 | Area Under the Blood Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-tlast) of M5717 | 1470 hour*ng/mL | Geometric Coefficient of Variation 4.65 |
| Early Liver Stage: 100 mg M5717 | Area Under the Blood Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-tlast) of M5717 | 7330 hour*ng/mL | Geometric Coefficient of Variation 42.8 |
| Early Liver Stage: 200 mg M5717 | Area Under the Blood Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-tlast) of M5717 | 657 hour*ng/mL | Geometric Coefficient of Variation 67.17 |
| Late Liver Stage: Pooled Placebo | Area Under the Blood Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-tlast) of M5717 | 1810 hour*ng/mL | Geometric Coefficient of Variation 8.09 |
| Late Liver Stage: 60 mg M5717 | Area Under the Blood Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-tlast) of M5717 | 3820 hour*ng/mL | Geometric Coefficient of Variation 70.38 |
Secondary
Blood Concentration at 168 Hours (C168) of M5717
C168 is the calculated blood concentration at 168 hours post-dose at which the measured blood concentration is at or above the Lower Limit of quantification (LLQ).
Time frame: At 168 hours post-dose
Population: PK analysis set included all participants, who received one dose of M5717, have no clinically important protocol deviations or important events affecting PK, \& provide at least one measurable post-dose concentration. Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Early Liver Stage: Pooled Placebo | Blood Concentration at 168 Hours (C168) of M5717 | NA ng/mL | — |
| Early Liver Stage: 30 mg M5717 | Blood Concentration at 168 Hours (C168) of M5717 | 2.89 ng/mL | Geometric Coefficient of Variation 38.61 |
| Early Liver Stage: 60 mg M5717 | Blood Concentration at 168 Hours (C168) of M5717 | 4.31 ng/mL | Geometric Coefficient of Variation 13.43 |
| Early Liver Stage: 80 mg M5717 | Blood Concentration at 168 Hours (C168) of M5717 | 4.16 ng/mL | Geometric Coefficient of Variation 24.6 |
| Early Liver Stage: 100 mg M5717 | Blood Concentration at 168 Hours (C168) of M5717 | 11.4 ng/mL | Geometric Coefficient of Variation 40.64 |
| Early Liver Stage: 200 mg M5717 | Blood Concentration at 168 Hours (C168) of M5717 | NA ng/mL | — |
| Late Liver Stage: Pooled Placebo | Blood Concentration at 168 Hours (C168) of M5717 | 4.88 ng/mL | Geometric Coefficient of Variation 2.5 |
| Late Liver Stage: 60 mg M5717 | Blood Concentration at 168 Hours (C168) of M5717 | 8.30 ng/mL | Geometric Coefficient of Variation 45.6 |
Secondary
Blood Concentration at 24 Hours (C24) of M5717
Blood samples for PK analysis of C24 of M5717 was reported.
Time frame: At 24 hours post-dose
Population: Pharmacokinetic analysis set included all participants, who received one dose of M5717, have no clinically important protocol deviations or important events affecting PK, and provide at least one measurable post-dose concentration. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Early Liver Stage: Pooled Placebo | Blood Concentration at 24 Hours (C24) of M5717 | NA ng/mL | — |
| Early Liver Stage: 30 mg M5717 | Blood Concentration at 24 Hours (C24) of M5717 | 6.77 ng/mL | Geometric Coefficient of Variation 45.35 |
| Early Liver Stage: 60 mg M5717 | Blood Concentration at 24 Hours (C24) of M5717 | 9.42 ng/mL | Geometric Coefficient of Variation 28.12 |
| Early Liver Stage: 80 mg M5717 | Blood Concentration at 24 Hours (C24) of M5717 | 11.3 ng/mL | Geometric Coefficient of Variation 31.42 |
| Early Liver Stage: 100 mg M5717 | Blood Concentration at 24 Hours (C24) of M5717 | 30.6 ng/mL | Geometric Coefficient of Variation 24.91 |
| Early Liver Stage: 200 mg M5717 | Blood Concentration at 24 Hours (C24) of M5717 | 6.06 ng/mL | Geometric Coefficient of Variation 37.89 |
| Late Liver Stage: Pooled Placebo | Blood Concentration at 24 Hours (C24) of M5717 | 14.9 ng/mL | Geometric Coefficient of Variation 14.56 |
| Late Liver Stage: 60 mg M5717 | Blood Concentration at 24 Hours (C24) of M5717 | 26.7 ng/mL | Geometric Coefficient of Variation 37.88 |
Secondary
Elimination Rate Constant (Lambda z) of M5717
Elimination rate constant determined from the terminal slope of the log-transformed concentration curve using linear regression on terminal data points of the curve.
Time frame: Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 120, 168, 192, 600, and 768 hours post-dose
Population: PK analysis set included all participants, who received 1 dose of M5717, had no clinically important protocol deviations/important events affecting PK, \& provide at least 1 measurable post-dose concentration. Data was not available for 'Early liver stage: 30 mg M5717' arm as no participants were considered evaluable because of limited number of samples collected to characterize the elimination rate constant (lambda z).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Early Liver Stage: 30 mg M5717 | Elimination Rate Constant (Lambda z) of M5717 | 0.00597 One per Hours (1/h) | Geometric Coefficient of Variation 22.93 |
| Early Liver Stage: 60 mg M5717 | Elimination Rate Constant (Lambda z) of M5717 | 0.00529 One per Hours (1/h) | Geometric Coefficient of Variation 30.44 |
| Early Liver Stage: 80 mg M5717 | Elimination Rate Constant (Lambda z) of M5717 | 0.00885 One per Hours (1/h) | Geometric Coefficient of Variation 28.59 |
| Early Liver Stage: 100 mg M5717 | Elimination Rate Constant (Lambda z) of M5717 | 0.00182 One per Hours (1/h) | Geometric Coefficient of Variation 55.45 |
| Early Liver Stage: 200 mg M5717 | Elimination Rate Constant (Lambda z) of M5717 | 0.00677 One per Hours (1/h) | Geometric Coefficient of Variation 38.43 |
| Late Liver Stage: Pooled Placebo | Elimination Rate Constant (Lambda z) of M5717 | 0.00786 One per Hours (1/h) | Geometric Coefficient of Variation 12.78 |
| Late Liver Stage: 60 mg M5717 | Elimination Rate Constant (Lambda z) of M5717 | 0.00511 One per Hours (1/h) | Geometric Coefficient of Variation 30.5 |
Secondary
Maximum Observed Blood Concentration (Cmax) of M5717
Cmax was obtained directly from the concentration versus time curve.
Time frame: Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 120, 168, 192, 600, and 768 hours post-dose
Population: Pharmacokinetic analysis set included all participants, who received one dose of M5717, have no clinically important protocol deviations or important events affecting PK, and provide at least one measurable post-dose concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Early Liver Stage: Pooled Placebo | Maximum Observed Blood Concentration (Cmax) of M5717 | 3.56 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 39.9 |
| Early Liver Stage: 30 mg M5717 | Maximum Observed Blood Concentration (Cmax) of M5717 | 11.7 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 36.93 |
| Early Liver Stage: 60 mg M5717 | Maximum Observed Blood Concentration (Cmax) of M5717 | 16.6 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 33.7 |
| Early Liver Stage: 80 mg M5717 | Maximum Observed Blood Concentration (Cmax) of M5717 | 17.2 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 44.12 |
| Early Liver Stage: 100 mg M5717 | Maximum Observed Blood Concentration (Cmax) of M5717 | 57.2 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 38.08 |
| Early Liver Stage: 200 mg M5717 | Maximum Observed Blood Concentration (Cmax) of M5717 | 9.38 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 82.5 |
| Late Liver Stage: Pooled Placebo | Maximum Observed Blood Concentration (Cmax) of M5717 | 27.6 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 22.19 |
| Late Liver Stage: 60 mg M5717 | Maximum Observed Blood Concentration (Cmax) of M5717 | 64.4 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 46.26 |
Secondary
Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings
Single 12-lead ECG was obtained as outlined using an ECG machine that automatically calculates the heart rate and measures PR, QRS, and QT intervals. Number of participants with clinically significant changes from baseline in ECG which were deemed clinically significant by the investigator were reported.
Time frame: Early Liver Stage: From Day 1 up to Day 33; Late Liver Stage: From Day 1 up to Day 36
Population: SAF included all ITT participants, who have been inoculated using a DVI of PfSPZ and who were administered one dose of study intervention (M5717 or placebo)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Early Liver Stage: Pooled Placebo | Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings | 0 Participants |
| Early Liver Stage: 30 mg M5717 | Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings | 0 Participants |
| Early Liver Stage: 60 mg M5717 | Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings | 0 Participants |
| Early Liver Stage: 80 mg M5717 | Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings | 0 Participants |
| Early Liver Stage: 100 mg M5717 | Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings | 0 Participants |
| Early Liver Stage: 200 mg M5717 | Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings | 0 Participants |
| Late Liver Stage: Pooled Placebo | Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings | 0 Participants |
| Late Liver Stage: 60 mg M5717 | Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings | 0 Participants |
| Late Liver Stage: 100 mg M5717 | Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings | 0 Participants |
| Late Liver Stage: 200 mg M5717 | Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings | 0 Participants |
Secondary
Number of Participants With Clinically Significant Change From Baseline in Laboratory Values
Laboratory assessments included hematology, biochemistry, urinalysis, and coagulation. Number of participants with clinically significant changes from baseline in laboratory values which were deemed clinically significant by the investigator were reported.
Time frame: Early Liver Stage: From Day 1 up to Day 33; Late Liver Stage: From Day 1 up to Day 36
Population: SAF included all ITT participants, who have been inoculated using a DVI of PfSPZ and who were administered one dose of study intervention (M5717 or placebo).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Early Liver Stage: Pooled Placebo | Number of Participants With Clinically Significant Change From Baseline in Laboratory Values | 0 Participants |
| Early Liver Stage: 30 mg M5717 | Number of Participants With Clinically Significant Change From Baseline in Laboratory Values | 0 Participants |
| Early Liver Stage: 60 mg M5717 | Number of Participants With Clinically Significant Change From Baseline in Laboratory Values | 0 Participants |
| Early Liver Stage: 80 mg M5717 | Number of Participants With Clinically Significant Change From Baseline in Laboratory Values | 0 Participants |
| Early Liver Stage: 100 mg M5717 | Number of Participants With Clinically Significant Change From Baseline in Laboratory Values | 0 Participants |
| Early Liver Stage: 200 mg M5717 | Number of Participants With Clinically Significant Change From Baseline in Laboratory Values | 0 Participants |
| Late Liver Stage: Pooled Placebo | Number of Participants With Clinically Significant Change From Baseline in Laboratory Values | 0 Participants |
| Late Liver Stage: 60 mg M5717 | Number of Participants With Clinically Significant Change From Baseline in Laboratory Values | 0 Participants |
| Late Liver Stage: 100 mg M5717 | Number of Participants With Clinically Significant Change From Baseline in Laboratory Values | 0 Participants |
| Late Liver Stage: 200 mg M5717 | Number of Participants With Clinically Significant Change From Baseline in Laboratory Values | 0 Participants |
Secondary
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Vital signs included oral body temperature, height, weight, systolic blood pressure, diastolic blood pressure, and pulse rate. Number of participants with clinically significant changes from baseline in Vital signs which were deemed clinically significant by the investigator were reported.
Time frame: Early Liver Stage: From Day 1 up to Day 33; Late Liver Stage: From Day 1 up to Day 36
Population: SAF included all ITT participants, who have been inoculated using a DVI of PfSPZ and who were administered one dose of study intervention (M5717 or placebo).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Early Liver Stage: Pooled Placebo | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 Participants |
| Early Liver Stage: 30 mg M5717 | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 Participants |
| Early Liver Stage: 60 mg M5717 | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 Participants |
| Early Liver Stage: 80 mg M5717 | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 Participants |
| Early Liver Stage: 100 mg M5717 | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 Participants |
| Early Liver Stage: 200 mg M5717 | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 Participants |
| Late Liver Stage: Pooled Placebo | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 Participants |
| Late Liver Stage: 60 mg M5717 | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 Participants |
| Late Liver Stage: 100 mg M5717 | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 Participants |
| Late Liver Stage: 200 mg M5717 | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Based on Severity
Severity of adverse events (AE) were assessed by the investigator per the Qualitative Toxicity Scale. Grade 1= Mild, Grade 2=Moderate, Grade 3=Severe. The number of participants that experienced at least one solicited local TEAE were summarized by grade. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. TEAEs include both Serious TEAEs and non-serious TEAEs. Number of participants with Grade=1, Grade=2 and 3 were reported.
Time frame: Early Liver Stage: From Day 1 up to Day 33; Late Liver Stage: From Day 1 up to Day 36
Population: SAF included all ITT participants, who have been inoculated using a Direct Intravenous Inoculation (DVI) of PfSPZ and who were administered one dose of study intervention (M5717 or placebo).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Early Liver Stage: Pooled Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Based on Severity | Grade 3 (Severe) | 0 Participants |
| Early Liver Stage: Pooled Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Based on Severity | Grade 2 (Moderate) | 3 Participants |
| Early Liver Stage: Pooled Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Based on Severity | Grade 1 (Mild) | 5 Participants |
| Early Liver Stage: 30 mg M5717 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Based on Severity | Grade 3 (Severe) | 0 Participants |
| Early Liver Stage: 30 mg M5717 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Based on Severity | Grade 2 (Moderate) | 2 Participants |
| Early Liver Stage: 30 mg M5717 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Based on Severity | Grade 1 (Mild) | 3 Participants |
| Early Liver Stage: 60 mg M5717 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Based on Severity | Grade 2 (Moderate) | 2 Participants |
| Early Liver Stage: 60 mg M5717 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Based on Severity | Grade 1 (Mild) | 6 Participants |
| Early Liver Stage: 60 mg M5717 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Based on Severity | Grade 3 (Severe) | 0 Participants |
| Early Liver Stage: 80 mg M5717 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Based on Severity | Grade 2 (Moderate) | 1 Participants |
| Early Liver Stage: 80 mg M5717 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Based on Severity | Grade 1 (Mild) | 6 Participants |
| Early Liver Stage: 80 mg M5717 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Based on Severity | Grade 3 (Severe) | 0 Participants |
| Early Liver Stage: 100 mg M5717 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Based on Severity | Grade 3 (Severe) | 1 Participants |
| Early Liver Stage: 100 mg M5717 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Based on Severity | Grade 1 (Mild) | 3 Participants |
| Early Liver Stage: 100 mg M5717 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Based on Severity | Grade 2 (Moderate) | 0 Participants |
| Early Liver Stage: 200 mg M5717 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Based on Severity | Grade 1 (Mild) | 3 Participants |
| Early Liver Stage: 200 mg M5717 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Based on Severity | Grade 3 (Severe) | 0 Participants |
| Early Liver Stage: 200 mg M5717 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Based on Severity | Grade 2 (Moderate) | 1 Participants |
| Late Liver Stage: Pooled Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Based on Severity | Grade 2 (Moderate) | 2 Participants |
| Late Liver Stage: Pooled Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Based on Severity | Grade 3 (Severe) | 0 Participants |
| Late Liver Stage: Pooled Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Based on Severity | Grade 1 (Mild) | 3 Participants |
| Late Liver Stage: 60 mg M5717 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Based on Severity | Grade 2 (Moderate) | 0 Participants |
| Late Liver Stage: 60 mg M5717 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Based on Severity | Grade 3 (Severe) | 0 Participants |
| Late Liver Stage: 60 mg M5717 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Based on Severity | Grade 1 (Mild) | 3 Participants |
| Late Liver Stage: 100 mg M5717 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Based on Severity | Grade 2 (Moderate) | 0 Participants |
| Late Liver Stage: 100 mg M5717 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Based on Severity | Grade 1 (Mild) | 2 Participants |
| Late Liver Stage: 100 mg M5717 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Based on Severity | Grade 3 (Severe) | 1 Participants |
| Late Liver Stage: 200 mg M5717 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Based on Severity | Grade 1 (Mild) | 2 Participants |
| Late Liver Stage: 200 mg M5717 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Based on Severity | Grade 2 (Moderate) | 0 Participants |
| Late Liver Stage: 200 mg M5717 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Based on Severity | Grade 3 (Severe) | 0 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-related TEAEs
An adverse event (AE) was defined as any untoward medical occurrence in a participant administered with study drug which does not necessarily had a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE was defined as AEs starting or worsening after the first intake of the study drug. TEAEs included both serious TEAEs and non-serious TEAEs. Treatment-related TEAEs: reasonably related to study intervention.
Time frame: Early Liver Stage: From Day 1 up to Day 33; Late Liver Stage: From Day 1 up to Day 36
Population: SAF included all ITT participants, who have been inoculated using a Direct Intravenous Inoculation (DVI) of PfSPZ and who were administered one dose of study intervention (M5717 or placebo).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Early Liver Stage: Pooled Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-related TEAEs | Participants with TEAEs | 5 Participants |
| Early Liver Stage: Pooled Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-related TEAEs | Participants with Treatment-related TEAEs | 2 Participants |
| Early Liver Stage: Pooled Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-related TEAEs | Participants with Serious TEAEs | 0 Participants |
| Early Liver Stage: 30 mg M5717 | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-related TEAEs | Participants with Serious TEAEs | 0 Participants |
| Early Liver Stage: 30 mg M5717 | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-related TEAEs | Participants with Treatment-related TEAEs | 0 Participants |
| Early Liver Stage: 30 mg M5717 | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-related TEAEs | Participants with TEAEs | 3 Participants |
| Early Liver Stage: 60 mg M5717 | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-related TEAEs | Participants with TEAEs | 6 Participants |
| Early Liver Stage: 60 mg M5717 | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-related TEAEs | Participants with Treatment-related TEAEs | 2 Participants |
| Early Liver Stage: 60 mg M5717 | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-related TEAEs | Participants with Serious TEAEs | 0 Participants |
| Early Liver Stage: 80 mg M5717 | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-related TEAEs | Participants with TEAEs | 6 Participants |
| Early Liver Stage: 80 mg M5717 | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-related TEAEs | Participants with Treatment-related TEAEs | 2 Participants |
| Early Liver Stage: 80 mg M5717 | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-related TEAEs | Participants with Serious TEAEs | 0 Participants |
| Early Liver Stage: 100 mg M5717 | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-related TEAEs | Participants with Serious TEAEs | 0 Participants |
| Early Liver Stage: 100 mg M5717 | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-related TEAEs | Participants with TEAEs | 3 Participants |
| Early Liver Stage: 100 mg M5717 | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-related TEAEs | Participants with Treatment-related TEAEs | 1 Participants |
| Early Liver Stage: 200 mg M5717 | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-related TEAEs | Participants with Serious TEAEs | 0 Participants |
| Early Liver Stage: 200 mg M5717 | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-related TEAEs | Participants with TEAEs | 3 Participants |
| Early Liver Stage: 200 mg M5717 | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-related TEAEs | Participants with Treatment-related TEAEs | 3 Participants |
| Late Liver Stage: Pooled Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-related TEAEs | Participants with TEAEs | 3 Participants |
| Late Liver Stage: Pooled Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-related TEAEs | Participants with Treatment-related TEAEs | 0 Participants |
| Late Liver Stage: Pooled Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-related TEAEs | Participants with Serious TEAEs | 0 Participants |
| Late Liver Stage: 60 mg M5717 | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-related TEAEs | Participants with Serious TEAEs | 0 Participants |
| Late Liver Stage: 60 mg M5717 | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-related TEAEs | Participants with Treatment-related TEAEs | 1 Participants |
| Late Liver Stage: 60 mg M5717 | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-related TEAEs | Participants with TEAEs | 3 Participants |
| Late Liver Stage: 100 mg M5717 | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-related TEAEs | Participants with Serious TEAEs | 0 Participants |
| Late Liver Stage: 100 mg M5717 | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-related TEAEs | Participants with TEAEs | 2 Participants |
| Late Liver Stage: 100 mg M5717 | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-related TEAEs | Participants with Treatment-related TEAEs | 0 Participants |
| Late Liver Stage: 200 mg M5717 | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-related TEAEs | Participants with Serious TEAEs | 0 Participants |
| Late Liver Stage: 200 mg M5717 | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-related TEAEs | Participants with Treatment-related TEAEs | 0 Participants |
| Late Liver Stage: 200 mg M5717 | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-related TEAEs | Participants with TEAEs | 2 Participants |
Secondary
Time to Reach Maximum Blood Concentration (Tmax) of M5717
Time to reach the maximum blood concentration (Tmax) was obtained directly from the concentration versus time curve.
Time frame: Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 120, 168, 192, 600, and 768 hours post-dose
Population: Pharmacokinetic analysis set included all participants, who received one dose of M5717, have no clinically important protocol deviations or important events affecting PK, and provide at least one measurable post-dose concentration.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Early Liver Stage: Pooled Placebo | Time to Reach Maximum Blood Concentration (Tmax) of M5717 | 6.00 Hours |
| Early Liver Stage: 30 mg M5717 | Time to Reach Maximum Blood Concentration (Tmax) of M5717 | 1.00 Hours |
| Early Liver Stage: 60 mg M5717 | Time to Reach Maximum Blood Concentration (Tmax) of M5717 | 3.25 Hours |
| Early Liver Stage: 80 mg M5717 | Time to Reach Maximum Blood Concentration (Tmax) of M5717 | 6.00 Hours |
| Early Liver Stage: 100 mg M5717 | Time to Reach Maximum Blood Concentration (Tmax) of M5717 | 1.00 Hours |
| Early Liver Stage: 200 mg M5717 | Time to Reach Maximum Blood Concentration (Tmax) of M5717 | 1.00 Hours |
| Late Liver Stage: Pooled Placebo | Time to Reach Maximum Blood Concentration (Tmax) of M5717 | 2.00 Hours |
| Late Liver Stage: 60 mg M5717 | Time to Reach Maximum Blood Concentration (Tmax) of M5717 | 2.00 Hours |