Malaria, Plasmodium Falciparum Infection
Conditions
Keywords
Malaria, Plasmodium falciparum, L9LS, Monoclonal antibodies
Brief summary
The purpose of this study is to evaluate the safety and tolerability of a one time SC administration of L9LS in healthy adults in Mali, as well as its protective efficacy against naturally occurring Plasmodium falciparum (Pf) infection over a 6-month malaria season. A secondary objective is to determine if SC administration of L9LS at 900 mg (compared to placebo) mediates protection against naturally occurring Pf infection in healthy Malian adult females stratified by weight during a single malaria season.
Detailed description
A phase 2 trial evaluating the safety and tolerability of a one time subcutaneous (SC) administration of L9LS, as well its protective efficacy against naturally occurring Pf infection over a 6-month malaria season. The primary study hypotheses is that L9LS will be safe and protective against malaria infection. As a secondary objective, the efficacy of L9LS within three body weight strata among female participants will each be compared to placebo. Before study agent administration, all subjects will be given artemether lumefantrine to clear any preexisting Pf blood stage infection. The study is a randomized, double-blind, placebo-controlled, sex-stratified (2:1 female to male ratio) and weight-stratified trial (N=288 total) with 2 treatment arms: L9LS 900 mg SC (n=216) and placebo (n=72) to assess safety and protective efficacy of L9LS compared to placebo. Subjects will receive the study agent and be followed at study visits 1, 3, 7, 14, 21, and 28 days later, and once every 2 weeks thereafter through 24 weeks. Primary study assessments include physical examination and blood collection for identification of Pf infection and other research laboratory evaluations.
Interventions
BIOLOGICALL9LS (VRC-MALMAB0114-00-AB)
Administered one time via subcutaneous route.
OTHERPlacebo
Normal saline administered one time via subcutaneous route.
Sponsors
National Institutes of Health (NIH)
Malaria Research and Training Center, Bamako, Mali
University of the Sciences, Techniques and Technologies of Bamako
University of Washington
Harvard School of Public Health (HSPH)
Indiana University School of Medicine
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Females aged ≥18 and ≤49 years and weighing ≥ 45.0 and ≤ 90.0 kg. 2. Males aged ≥18 and ≤55 years and weighing ≥ 50.0 and ≤ 100.0 kg. 3. Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process. 4. In good general health and without clinically significant medical history. 5. Able to provide informed consent. 6. Willing to have blood samples and data stored for future research. 7. Resides in or near Kalifabougou, Faladje, or Torodo, Mali, and available for the duration of the study. 8. Females of childbearing potential must be willing to use reliable contraception from 21 days prior to study day 0 through the final study visit as described below. 1. Reliable methods of birth control include 1 of the following: confirmed pharmacologic contraceptives via parenteral delivery or intrauterine or implantable device. 2. Nonchildbearing women will be required to report date of last menstrual period, history of surgical sterility (i.e., tubal ligation, hysterectomy) or premature ovarian insufficiency, and will have urine or serum pregnancy tests performed per protocol.
Exclusion criteria
1. Pregnancy, as determined by a positive urine or serum beta-human choriogonadotropin (β hCG) test (if female). 2. Currently breastfeeding. 3. Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the subject to understand and comply with the study protocol. 4. Study comprehension examination score of \<80% correct or per investigator discretion. 5. Hemoglobin, white blood cell, absolute neutrophil, or platelet count outside the local laboratory-defined limits of normal. (Subjects may be included at the investigator's discretion for not clinically significant values.) 6. Alanine transaminase (ALT) or creatinine (Cr) level above the local laboratory-defined upper limit of normal. (Subjects may be included at the investigator's discretion for not clinically significant values.) 7. Infected with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV). 8. Known or documented sickle cell disease by history. (Note: Known sickle cell trait is NOT exclusionary.) 9. Clinically significant abnormal electrocardiogram (ECG; QTc \>460 or other significant abnormal findings, including unexplained tachycardia or bradycardia). 10. Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, endocrine, rheumatologic, autoimmune, hematological, oncologic, or renal disease by history, physical examination, and/or laboratory studies including urinalysis. 11. Receipt of any investigational product within the past 30 days. 12. Participation or planned participation in an interventional trial with an investigational product until the last required protocol visit. \[Note: Past, current, or planned participation in observational studies is NOT exclusionary; participation in the placebo arm of the Mali adult CIS43LS MAb trial (ClinicalTrials.gov Identifier: NCT04329104) is NOT exclusionary.\] 13. Medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months. 14. History of a severe allergic reaction or anaphylaxis. 15. Severe asthma (defined as asthma that is unstable or required emergent care, urgent care, hospitalization, or intubation during the past 2 years, or that has required the use of oral or parenteral corticosteroids at any time during the past 2 years). 16. Pre-existing autoimmune or antibody-mediated diseases including but not limited to: systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjögren's syndrome, or autoimmune thrombocytopenia. 17. Salivary gland disorder diagnosed by a doctor (e.g., parotitis, sialadenitis, sialolithiasis, salivary gland tumors). 18. Known immunodeficiency syndrome. 19. Known asplenia or functional asplenia. 20. Use of chronic (≥14 days) oral or IV corticosteroids (excluding topical or nasal) at immunosuppressive doses (i.e., prednisone \>10 mg/day) or immunosuppressive drugs within 30 days of day 0. 21. Receipt of a live vaccine within the past 4 weeks or a killed vaccine within the past 2 weeks prior to study agent administration. 22. Receipt of immunoglobulins and/or blood products within the past 6 months. 23. Previous receipt of an investigational malaria vaccine or monoclonal antibody in the last 5 years. 24. Known allergies or contraindication against artemether lumefantrine. 25. Other condition(s) that, in the opinion of the investigator, would jeopardize the safety or rights of a subject participating in the trial, interfere with the evaluation of the study objectives, or render the subject unable to comply with the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants With Plasmodium Falciparum (Pf) Infection Detected by Microscopic Examination for Thick Blood Smear | Day 7 through week 24 | Number of participants with Plasmodium falciparum (Pf) blood stage infection defined as blood smear-positive for Pf was assessed by microscopic examination of thick blood smear collected from participants from day 7 through week 24 (168 days) after administration of L9LS or placebo. Sample was collected every two weeks from day seven until week 24. Analysis was done as number of participants who had at least one positive blood smear. |
| Number of Participants With Local Adverse Events (AEs) | Within 7 days after administration of intervention | Number of participants with local adverse events occurring within 7 days after administration of L9LS. Local reactogenicity included pain/tenderness, swelling, redness, bruising, and pruritus at the site of infusion. Adverse events were captured by Investigator examination and history from participants. |
| Number of Participants With Systemic Adverse Events (AEs) | Within 7 days after administration of intervention | Number of participants with local adverse events occurring within 7 days after administration of L9LS. Systemic reactogenicity events included fever, feeling unusually tired or unwell, muscle aches, headache, chills, nausea, and joint pain. Adverse events were captured by Investigator examination and history from participants. |
| Number of Participants With Local Adverse Events (AEs) (by Grade) | Within 7 days after administration of intervention | The severity of local AEs was graded using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Clinical Trials Grade 1: Pain = does not interfere with activity; Tenderness = mild discomfort to touch; Erythema/Redness = 2.5-5 cm; Induration/Swelling = 2.5-5 cm and does not interfere with activity. Grade 2: Pain = Repeated use of non-narcotic pain reliever \> 24 hours or interferes with daily activity; Tenderness= Discomfort with movement; Erythema/Redness = 5.1-10 cm; Induration/Swelling = 5.1-10 cm and interferes with activity. Grade 3: Pain = Any use of narcotic pain reliever or prevents daily activity; Tenderness = Significant discomfort at rest; Erythema/Redness = \> 10 cm; Induration/Swelling = \> 10 cm or prevents daily activity. Grade 4: Pain = Emergency room (ER) visit or hospitalization; Tenderness = ER visit or hospitalization; Erythema/Redness = Necrosis or exfoliative dermatitis; induration/Swelling = Necrosis Grade 5: Death |
| Number of Participants With Systemic Adverse Events (AEs) (by Grade) | Within 7 days after administration of intervention | The severity of systemic adverse events occurring after the administration of L9LS was assessed using the grading scale below: Grade 1: Fever = 37.5\^oC-37.9\^oC; Fatigue, Headache, Myalgia = No interference with activity; Nausea = no interference with activity or 1-2 episodes/hour Grade 2: Fever = 38\^oC-38.4\^oC; Fatigue, Myalgia = Some interference with activity; Headache = Repeated use of non-narcotic pain reliever \> 24 hours or some interference with activity; Nausea = Some interference with activity or \> 2 episodes/24 hours Grade 3: Fever = 38.5\^oC-39.5\^oC; Fatigue = Prevents daily activity; Headache =Significant; any use of narcotic pain reliever or prevents daily activity; Myalgia =Significant; prevents daily activity; Nausea = Prevents daily activity, requires outpatient intravenous hydration Grade 4: Fever = \> 39.5\^oC; Fatigue, Headache, Myalgia = Emergency room (ER) visit or hospitalization; Nausea = ER visit or hospitalization for hypotensive shock Grade 5: Death |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Total Plasma Concentration (Cmax) for L9LS | Measure through week 24 | Maximum total plasma concentration (Cmax) following a 900 mg dose of L9LS. Serum collected on days 0, 1, 7, 14, 28, 56, 84, 112, 140, & 168 after the administration of L9LS. Cmax for L9LS was obtained directly by visual inspection of the plasma concentration versus time profiles postdose. Analysis was done to determine each participant's observed maximum concentration based on all available timepoints and cumulative output was calculated as the central tendency and dispersion metric based on the observed maximum concentrations. |
| Time to Maximum Plasma Concentration (TMax) for L9LS - Hours | Day 7 post administration of drug | Time to maximum total plasma concentration (Cmax) following a 900 mg dose of L9LS on day 7 post administration of drug. Tmax for L9LS was obtained directly by visual inspection of the plasma concentration versus time profiles. Analysis was done to determine the time (in hours) at which the maximum observed concentration was achieved for each participant and cumulative output was calculated as the central tendency and dispersion metric based on the observed time of maximum concentration. |
| Time to Maximum Plasma Concentration (TMax) for L9LS - Days | Measure through week 24 | Time to maximum total plasma concentration (Cmax) following a 900 mg dose of L9LS. Serum collected on days 0, 1, 7, 14, 28, 56, 84, 112, 140, & 168 after the administration of L9LS. Tmax for L9LS was obtained directly by visual inspection of the plasma concentration versus time profiles. Analysis was done to determine the time (in days) at which the maximum observed concentration was achieved for each participant and cumulative output was calculated as the central tendency and dispersion metric based on the observed time of maximum concentration. |
| Participants With Plasmodium Falciparum (Pf) Infection Detected by Real-Time Polymerase Chain Reaction (RT-PCR) | Day 7 through week 24 | Number of participants with Plasmodium falciparum (Pf) blood stage infection defined as blood sample positive for Pf was assessed by real-time polymerase chain reaction (RT-PCR) of blood sample collected from participants from day 7 through week 24 (168 days) after administration of L9LS or placebo. Sample was collected every two weeks from day seven until week 24. Analysis was done as number of participants who had at least one positive blood sample. |
Countries
Mali
Participant flow
Pre-assignment details
490 participants were consented: * 156 participants were screen failure and ineligible * 45 participants served as backup * One participant withdrew consent * 288 participants received intervention
Participants by arm
| Arm | Count |
|---|---|
| L9LS 900 mg Adult participants receive a single dose of L9LS 900 mg subcutaneously. | 217 |
| Placebo Adult participants receive a single dose of Placebo subcutaneously. | 71 |
| Total | 288 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 4 | 1 |
Baseline characteristics
| Characteristic | Placebo | L9LS 900 mg | Total |
|---|---|---|---|
| Age, Customized 18-20 years | 7 Participants | 31 Participants | 38 Participants |
| Age, Customized 21-30 years | 19 Participants | 61 Participants | 80 Participants |
| Age, Customized 31-40 years | 18 Participants | 72 Participants | 90 Participants |
| Age, Customized 41-49 years | 22 Participants | 48 Participants | 70 Participants |
| Age, Customized 50-55 years (Male only) | 5 Participants | 5 Participants | 10 Participants |
| Race/Ethnicity, Customized African | 71 Participants | 217 Participants | 288 Participants |
| Region of Enrollment Mali | 71 participants | 217 participants | 288 participants |
| Sex: Female, Male Female | 22 Participants | 74 Participants | 96 Participants |
| Sex: Female, Male Male | 49 Participants | 143 Participants | 192 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 217 | 0 / 71 |
| other Total, other adverse events | 192 / 217 | 57 / 71 |
| serious Total, serious adverse events | 0 / 217 | 1 / 71 |
Outcome results
Primary
Number of Participants With Local Adverse Events (AEs)
Number of participants with local adverse events occurring within 7 days after administration of L9LS. Local reactogenicity included pain/tenderness, swelling, redness, bruising, and pruritus at the site of infusion. Adverse events were captured by Investigator examination and history from participants.
Time frame: Within 7 days after administration of intervention
Population: All participants who received study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| L9LS 900 mg | Number of Participants With Local Adverse Events (AEs) | Bruising at injection site | 0 Participants |
| L9LS 900 mg | Number of Participants With Local Adverse Events (AEs) | Injection site swelling | 7 Participants |
| L9LS 900 mg | Number of Participants With Local Adverse Events (AEs) | Pain at Injection site | 0 Participants |
| L9LS 900 mg | Number of Participants With Local Adverse Events (AEs) | Tenderness at injection site | 0 Participants |
| L9LS 900 mg | Number of Participants With Local Adverse Events (AEs) | Redness at injection site | 0 Participants |
| L9LS 900 mg | Number of Participants With Local Adverse Events (AEs) | Pruritus at injection site | 0 Participants |
| Placebo | Number of Participants With Local Adverse Events (AEs) | Redness at injection site | 0 Participants |
| Placebo | Number of Participants With Local Adverse Events (AEs) | Bruising at injection site | 0 Participants |
| Placebo | Number of Participants With Local Adverse Events (AEs) | Tenderness at injection site | 0 Participants |
| Placebo | Number of Participants With Local Adverse Events (AEs) | Injection site swelling | 1 Participants |
| Placebo | Number of Participants With Local Adverse Events (AEs) | Pruritus at injection site | 0 Participants |
| Placebo | Number of Participants With Local Adverse Events (AEs) | Pain at Injection site | 0 Participants |
Primary
Number of Participants With Local Adverse Events (AEs) (by Grade)
The severity of local AEs was graded using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Clinical Trials Grade 1: Pain = does not interfere with activity; Tenderness = mild discomfort to touch; Erythema/Redness = 2.5-5 cm; Induration/Swelling = 2.5-5 cm and does not interfere with activity. Grade 2: Pain = Repeated use of non-narcotic pain reliever \> 24 hours or interferes with daily activity; Tenderness= Discomfort with movement; Erythema/Redness = 5.1-10 cm; Induration/Swelling = 5.1-10 cm and interferes with activity. Grade 3: Pain = Any use of narcotic pain reliever or prevents daily activity; Tenderness = Significant discomfort at rest; Erythema/Redness = \> 10 cm; Induration/Swelling = \> 10 cm or prevents daily activity. Grade 4: Pain = Emergency room (ER) visit or hospitalization; Tenderness = ER visit or hospitalization; Erythema/Redness = Necrosis or exfoliative dermatitis; induration/Swelling = Necrosis Grade 5: Death
Time frame: Within 7 days after administration of intervention
Population: All participants who received study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| L9LS 900 mg | Number of Participants With Local Adverse Events (AEs) (by Grade) | Grade 2 | 0 Participants |
| L9LS 900 mg | Number of Participants With Local Adverse Events (AEs) (by Grade) | Grade 4 | 0 Participants |
| L9LS 900 mg | Number of Participants With Local Adverse Events (AEs) (by Grade) | Grade 3 | 0 Participants |
| L9LS 900 mg | Number of Participants With Local Adverse Events (AEs) (by Grade) | Grade 5 | 0 Participants |
| L9LS 900 mg | Number of Participants With Local Adverse Events (AEs) (by Grade) | Grade 1 | 7 Participants |
| Placebo | Number of Participants With Local Adverse Events (AEs) (by Grade) | Grade 5 | 0 Participants |
| Placebo | Number of Participants With Local Adverse Events (AEs) (by Grade) | Grade 1 | 1 Participants |
| Placebo | Number of Participants With Local Adverse Events (AEs) (by Grade) | Grade 2 | 0 Participants |
| Placebo | Number of Participants With Local Adverse Events (AEs) (by Grade) | Grade 3 | 0 Participants |
| Placebo | Number of Participants With Local Adverse Events (AEs) (by Grade) | Grade 4 | 0 Participants |
Primary
Number of Participants With Systemic Adverse Events (AEs)
Number of participants with local adverse events occurring within 7 days after administration of L9LS. Systemic reactogenicity events included fever, feeling unusually tired or unwell, muscle aches, headache, chills, nausea, and joint pain. Adverse events were captured by Investigator examination and history from participants.
Time frame: Within 7 days after administration of intervention
Population: All participants who received study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| L9LS 900 mg | Number of Participants With Systemic Adverse Events (AEs) | Muscle aches | 0 Participants |
| L9LS 900 mg | Number of Participants With Systemic Adverse Events (AEs) | Chills | 0 Participants |
| L9LS 900 mg | Number of Participants With Systemic Adverse Events (AEs) | Malaise | 0 Participants |
| L9LS 900 mg | Number of Participants With Systemic Adverse Events (AEs) | Nausea | 2 Participants |
| L9LS 900 mg | Number of Participants With Systemic Adverse Events (AEs) | Headache | 21 Participants |
| L9LS 900 mg | Number of Participants With Systemic Adverse Events (AEs) | Joint pain | 0 Participants |
| L9LS 900 mg | Number of Participants With Systemic Adverse Events (AEs) | Fever | 1 Participants |
| Placebo | Number of Participants With Systemic Adverse Events (AEs) | Joint pain | 0 Participants |
| Placebo | Number of Participants With Systemic Adverse Events (AEs) | Fever | 0 Participants |
| Placebo | Number of Participants With Systemic Adverse Events (AEs) | Malaise | 0 Participants |
| Placebo | Number of Participants With Systemic Adverse Events (AEs) | Muscle aches | 0 Participants |
| Placebo | Number of Participants With Systemic Adverse Events (AEs) | Headache | 4 Participants |
| Placebo | Number of Participants With Systemic Adverse Events (AEs) | Chills | 2 Participants |
| Placebo | Number of Participants With Systemic Adverse Events (AEs) | Nausea | 0 Participants |
Primary
Number of Participants With Systemic Adverse Events (AEs) (by Grade)
The severity of systemic adverse events occurring after the administration of L9LS was assessed using the grading scale below: Grade 1: Fever = 37.5\^oC-37.9\^oC; Fatigue, Headache, Myalgia = No interference with activity; Nausea = no interference with activity or 1-2 episodes/hour Grade 2: Fever = 38\^oC-38.4\^oC; Fatigue, Myalgia = Some interference with activity; Headache = Repeated use of non-narcotic pain reliever \> 24 hours or some interference with activity; Nausea = Some interference with activity or \> 2 episodes/24 hours Grade 3: Fever = 38.5\^oC-39.5\^oC; Fatigue = Prevents daily activity; Headache =Significant; any use of narcotic pain reliever or prevents daily activity; Myalgia =Significant; prevents daily activity; Nausea = Prevents daily activity, requires outpatient intravenous hydration Grade 4: Fever = \> 39.5\^oC; Fatigue, Headache, Myalgia = Emergency room (ER) visit or hospitalization; Nausea = ER visit or hospitalization for hypotensive shock Grade 5: Death
Time frame: Within 7 days after administration of intervention
Population: All participants who received study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| L9LS 900 mg | Number of Participants With Systemic Adverse Events (AEs) (by Grade) | Grade 5 | 0 Participants |
| L9LS 900 mg | Number of Participants With Systemic Adverse Events (AEs) (by Grade) | Grade 1 | 11 Participants |
| L9LS 900 mg | Number of Participants With Systemic Adverse Events (AEs) (by Grade) | Grade 2 | 13 Participants |
| L9LS 900 mg | Number of Participants With Systemic Adverse Events (AEs) (by Grade) | Grade 3 | 0 Participants |
| L9LS 900 mg | Number of Participants With Systemic Adverse Events (AEs) (by Grade) | Grade 4 | 0 Participants |
| Placebo | Number of Participants With Systemic Adverse Events (AEs) (by Grade) | Grade 4 | 0 Participants |
| Placebo | Number of Participants With Systemic Adverse Events (AEs) (by Grade) | Grade 3 | 0 Participants |
| Placebo | Number of Participants With Systemic Adverse Events (AEs) (by Grade) | Grade 1 | 2 Participants |
| Placebo | Number of Participants With Systemic Adverse Events (AEs) (by Grade) | Grade 5 | 0 Participants |
| Placebo | Number of Participants With Systemic Adverse Events (AEs) (by Grade) | Grade 2 | 4 Participants |
Primary
Participants With Plasmodium Falciparum (Pf) Infection Detected by Microscopic Examination for Thick Blood Smear
Number of participants with Plasmodium falciparum (Pf) blood stage infection defined as blood smear-positive for Pf was assessed by microscopic examination of thick blood smear collected from participants from day 7 through week 24 (168 days) after administration of L9LS or placebo. Sample was collected every two weeks from day seven until week 24. Analysis was done as number of participants who had at least one positive blood smear.
Time frame: Day 7 through week 24
Population: All participants who received study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| L9LS 900 mg | Participants With Plasmodium Falciparum (Pf) Infection Detected by Microscopic Examination for Thick Blood Smear | 33 Participants |
| Placebo | Participants With Plasmodium Falciparum (Pf) Infection Detected by Microscopic Examination for Thick Blood Smear | 40 Participants |
Secondary
Maximum Total Plasma Concentration (Cmax) for L9LS
Maximum total plasma concentration (Cmax) following a 900 mg dose of L9LS. Serum collected on days 0, 1, 7, 14, 28, 56, 84, 112, 140, & 168 after the administration of L9LS. Cmax for L9LS was obtained directly by visual inspection of the plasma concentration versus time profiles postdose. Analysis was done to determine each participant's observed maximum concentration based on all available timepoints and cumulative output was calculated as the central tendency and dispersion metric based on the observed maximum concentrations.
Time frame: Measure through week 24
Population: Per protocol document, measure apply to participants who received L9LS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| L9LS 900 mg | Maximum Total Plasma Concentration (Cmax) for L9LS | 158.07 ug/mL | Standard Deviation 30.41 |
Secondary
Participants With Plasmodium Falciparum (Pf) Infection Detected by Real-Time Polymerase Chain Reaction (RT-PCR)
Number of participants with Plasmodium falciparum (Pf) blood stage infection defined as blood sample positive for Pf was assessed by real-time polymerase chain reaction (RT-PCR) of blood sample collected from participants from day 7 through week 24 (168 days) after administration of L9LS or placebo. Sample was collected every two weeks from day seven until week 24. Analysis was done as number of participants who had at least one positive blood sample.
Time frame: Day 7 through week 24
Population: All participants who received study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| L9LS 900 mg | Participants With Plasmodium Falciparum (Pf) Infection Detected by Real-Time Polymerase Chain Reaction (RT-PCR) | 68 Participants |
| Placebo | Participants With Plasmodium Falciparum (Pf) Infection Detected by Real-Time Polymerase Chain Reaction (RT-PCR) | 43 Participants |
Secondary
Time to Maximum Plasma Concentration (TMax) for L9LS - Days
Time to maximum total plasma concentration (Cmax) following a 900 mg dose of L9LS. Serum collected on days 0, 1, 7, 14, 28, 56, 84, 112, 140, & 168 after the administration of L9LS. Tmax for L9LS was obtained directly by visual inspection of the plasma concentration versus time profiles. Analysis was done to determine the time (in days) at which the maximum observed concentration was achieved for each participant and cumulative output was calculated as the central tendency and dispersion metric based on the observed time of maximum concentration.
Time frame: Measure through week 24
Population: Per protocol document, measure apply to participants who received L9LS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| L9LS 900 mg | Time to Maximum Plasma Concentration (TMax) for L9LS - Days | 7.20 Days | Standard Deviation 1.25 |
Secondary
Time to Maximum Plasma Concentration (TMax) for L9LS - Hours
Time to maximum total plasma concentration (Cmax) following a 900 mg dose of L9LS on day 7 post administration of drug. Tmax for L9LS was obtained directly by visual inspection of the plasma concentration versus time profiles. Analysis was done to determine the time (in hours) at which the maximum observed concentration was achieved for each participant and cumulative output was calculated as the central tendency and dispersion metric based on the observed time of maximum concentration.
Time frame: Day 7 post administration of drug
Population: Per protocol document, measure apply to participants who received L9LS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| L9LS 900 mg | Time to Maximum Plasma Concentration (TMax) for L9LS - Hours | 172.9 Hours | Standard Deviation 30 |