Trial to Evaluate CIS43LS in Healthy Adults

Participants recorded the occurrence of solicited symptoms on a diary card for 7 days after study product administration and reviewed the diary card with clinic staff at a follow up visit. Participants were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time at any severity during the reporting period. The number reported for Any Local Symptom is the number of participants reporting any local symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1.

Time frame: 7 days after CIS43LS product administration, at approximately Week 1

Population: Population included all enrolled participants who received CIS43LS and provided safety data (via diary card). A subgroup of 4 participants from Part A who continued to Part B are counted twice, and received a second CIS43LS dose intravenously (IV): 4 received CIS43LS at a dose of 20 mg/kg IV in Part B (1 had previously received 5 mg/kg IV, 1 had received 5 mg/kg subcutaneously, and 2 had received 20 mg/kg IV). No participants enrolled in Group 6: CIS43LS (5 mg/kg SC).

Participants recorded the occurrence of solicited symptoms on a diary card for 7 days after study product administration and reviewed the diary card with clinic staff at a follow up visit. Participants were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time at any severity during the reporting period. The number reported for Any Systemic Symptom is the number of participants reporting any systemic symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1.

Time frame: 7 days after CIS43LS product administration, at approximately Week 1

Population: Population included all enrolled participants who received CIS43LS and provided safety data (via diary card). A subgroup of 4 participants from Part A who continued to Part B are counted twice, and received a second CIS43LS dose intravenously (IV): 4 received CIS43LS at a dose of 20 mg/kg IV in Part B (1 had previously received 5 mg/kg IV, 1 had received 5 mg/kg subcutaneously, and 2 had received 20 mg/kg IV). No participants enrolled in Group 6: CIS43LS (5 mg/kg SC).

Abnormal laboratory results recorded as unsolicited adverse events (AEs) are summarized. Safety lab parameters included hematology (hemoglobin, hematocrit, mean corpuscular volume (MCV) platelets, and white blood cell (WBC), red blood cell (RBC), neutrophil, lymphocyte, monocyte, eosinophil and basophil counts) and chemistry (alanine aminotransferase (ALT) and creatinine). Complete Blood Count (CBC) with differential and Chemistry (ALT and creatinine) results were collected at different timepoints in Parts A, B and C throughout the study per the protocol's schedule of evaluations. Institutional laboratory normal ranges as well as the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1 were used.

Time frame: Day 0 through 4 weeks after CIS43LS product administration

Population: Population included all enrolled participants who received CIS43LS and had safety data collected via laboratory results. A subgroup of 4 participants from Part A who continued to Part B are counted twice, and received a second CIS43LS dose intravenously (IV): 4 received CIS43LS at a dose of 20 mg/kg IV in Part B (1 had previously received 5 mg/kg IV, 1 had received 5 mg/kg subcutaneously, and 2 had received 20 mg/kg IV). No participants enrolled in Group 6: CIS43LS (5 mg/kg SC).

New chronic medical conditions that required ongoing medical management were recorded from receipt of first study product administration through the last expected study visit at Week 24. The relationship between a new chronic medical condition and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity.

Time frame: Day 0 after CIS43LS product administration through the study participation, up to Week 24

Population: Population included all enrolled participants who received CIS43LS and had safety data collected (via clinical assessment and/or lab results). A subgroup of 4 participants from Part A who continued to Part B are counted twice, and received a second CIS43LS dose intravenously (IV): 4 received CIS43LS at a dose of 20 mg/kg IV in Part B (1 had previously received 5 mg/kg IV, 1 received 5 mg/kg subcutaneously, and 2 received 20 mg/kg IV). No participants enrolled in Group 6: CIS43LS (5 mg/kg SC).

Unsolicited adverse event (AE) data collection included AEs of all severities from the date of product administration through the Day 28 post-product administration visit. At other time periods between study product administration and when greater than 4 weeks after the study product administration, only serious AEs (SAEs reported as a separate outcome and in the AE module) and new chronic medical conditions that required ongoing medical management (reported as a separate outcome) were recorded through the last study visit. The relationship between an AE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity.

Time frame: Day 0 through 4 weeks after CIS43LS product administration

Population: Population included all enrolled participants who received CIS43LS and had safety data collected (via clinical assessment and/or lab results). A subgroup of 4 participants from Part A who continued to Part B are counted twice, and received a second CIS43LS dose intravenously (IV): 4 received CIS43LS at a dose of 20 mg/kg IV in Part B (1 had previously received 5 mg/kg IV, 1 received 5 mg/kg subcutaneously, and 2 received 20 mg/kg IV). No participants enrolled in Group 6: CIS43LS (5 mg/kg SC).

Unsolicited adverse event (AE) data collection included AEs of all severities from CHMI through the Day 28 post-CHMI visit. The relationship between an AE and CHMI was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity.

Time frame: Day 0 through 4 weeks after CHMI

Population: Population included all enrolled participants who completed CHMI and had safety data collected (via clinical assessment and/or laboratory results). Part A participants did not complete CHMI because of restrictions related to coronavirus disease 2019 (COVID-19). No participants enrolled in Part B, Group 6: CIS43LS (5 mg/kg SC).

SAEs were recorded from receipt of first study product administration through the last expected study visit at Week 24. The relationship between a SAE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity.

Time frame: Day 0 after CIS43LS product administration through the study participation, up to Week 24

Population: Population included all enrolled participants who received CIS43LS and had safety data collected (via clinical assessment and/or lab results). A subgroup of 4 participants from Part A who continued to Part B are counted twice, and received a second CIS43LS dose intravenously (IV): 4 received CIS43LS at a dose of 20 mg/kg IV in Part B (1 had previously received 5 mg/kg IV, 1 received 5 mg/kg subcutaneously, and 2 received 20 mg/kg IV). No participants enrolled in Group 6: CIS43LS (5 mg/kg SC).

Parasitemia as determined by polymerase chain reaction (PCR) up to day 21 following CHMI to determine whether IV or SC administration of CIS43LS mediates protection against infectious P. falciparum following CHMI

Time frame: Up to 21 days after CHMI

Population: Population included all participants in Part B who completed CHMI. Part A participants did not complete CHMI because of restrictions related to COVID-19. A subgroup of 4 study participants received 2 doses of CIS43LS: 1 received 5 mg/kg IV and 2 received 20 mg/kg in Part A of the study and received second antibody administration at 20 mg/kg IV in Part B of the study; 1 received 5 mg/kg SC in Part A and 20 mg/kg IV in Part B of the study. No participants enrolled in Group 6: CIS43LS (5 mg/kg SC).

Parasitemia as determined by polymerase chain reaction (PCR) up to day 21 following CHMI to determine the lowest dose of CIS43LS administered IV and SC that confers protection against infectious P. falciparum following CHMI in Part C of the study

Time frame: Up to 21 days after CHMI

Population: Population included all participants in Part C who completed CHMI.

Beta half-life (T1/2b) is being reported for this study. Beta half-life (T1/2b) is the time required for half of the CIS43LS product to be eliminated from the serum. A two-compartmental population pharmacokinetic model with first order SC absorption was used to estimate overall beta half-life and bootstrap 90% confidence intervals (CIs).

Time frame: Baseline through 24 weeks after CIS43LS product administration

Population: Population included all enrolled participants who received CIS43LS subcutaneously and intravenously in Part A and/or Part B of the study with up to 24 weeks of pharmacokinetic. Due to pandemic related sample collection interruptions, Part A and Part B of the study were analyzed in conjunction to achieve adequate sample size for population pharmacokinetic model used to generate the population PK parameters as per protocol, including beta half-life and clearance.

Beta half-life (T1/2b) is the time required for half of the CIS43LS product to be eliminated from the serum. A two-compartmental population pharmacokinetic model with first order SC absorption was used to estimate overall beta half-life and bootstrap 95% confidence intervals (CIs).

Time frame: Baseline through 24 weeks after CIS43LS product administration

Population: Population included 22 enrolled participants who received CIS43LS: 21 CIS43LS participants with 24 weeks of pharmacokinetic (PK) data and one CIS43LS participant with 8 weeks of data (N=22). The participant with 8 weeks of data was assigned to the 10 mg/kg IV dose group and withdrew from the study at Day 15 post-CHMI. Per protocol, population PK analysis was performed to generate compartmental PK parameters, including clearance and half-life.

Rate of CIS43LS elimination divided by the plasma CIS43LS concentration; determined based on the summary pharmacokinetic (PK) curve for each study group. A two-compartmental population pharmacokinetic model with first order SC absorption was used to estimate overall clearance and bootstrap 90% confidence intervals (CIs).

Time frame: Baseline through 24 weeks after CIS43LS product administration

Population: Population included all enrolled participants who received CIS43LS subcutaneously and intravenously in Part A and/or Part B of the study with up to 24 weeks of pharmacokinetic (PK) data (N=29). Due to pandemic related sample collection interruptions, Part A and Part B of the study were analyzed in conjunction to achieve adequate sample size for population pharmacokinetic model used to generate the population PK parameters as per protocol, including beta half-life and clearance.

Rate of CIS43LS elimination divided by the plasma CIS43LS concentration; determined based on the summary pharmacokinetic (PK) curve for each study group. A two-compartmental population pharmacokinetic model with first order SC absorption was used to estimate overall clearance and bootstrap 95% confidence intervals (CIs).

Time frame: Baseline through 24 weeks after CIS43LS product administration

Population: Population included 22 enrolled participants who received CIS43LS: 21 CIS43LS participants with 24 weeks of pharmacokinetic (PK) data and one CIS43LS participant with 8 weeks of data (N=22). The participant with 8 weeks of data was assigned to the 10 mg/kg IV dose group and withdrew from the study at Day 15 post-CHMI. Per protocol, population PK analysis was performed to generate compartmental PK parameters, including clearance and half-life.

Serum concentrations of CIS43LS by dose group following a single administration. Cmax is the peak serum concentration that CIS43LS achieves after it has been administered; it is determined as a maximum value on the summary pharmacokinetic (PK) curve for each study group. After subcutaneous injection, Cmax could not be fully calculated because of COVID-19-related interruptions in sample collection.

Time frame: Baseline through 24 weeks after CIS43LS product administration

Population: Population included all enrolled participants who received CIS43LS intravenously in Part A and/or Part B of the study with up to 24 weeks of pharmacokinetic data (N=25). The 5 mg/kg SC dose group could not be evaluated due to truncated sample collections. Data in the 20 mg/kg IV dose group included 1 who received 5 mg/kg IV, 1 who received 5 mg/kg SC, and 2 who received 20 mg/kg IV in Part A of the study and received a second dose of CIS43LS at 20 mg/kg of body weight in Part B of the study.

Serum concentrations of CIS43LS by dose group following a single administration. Cmax is the peak serum concentration that CIS43LS achieves after it has been administered; it is determined as a maximum value on the summary pharmacokinetic (PK) curve for each study group.

Time frame: Baseline through 24 weeks after CIS43LS product administration

Population: Population included 22 enrolled participants who received CIS43LS: 21 CIS43LS participants with 24 weeks of pharmacokinetic data and one CIS43LS participant with 8 weeks of data (N=22). The participant with 8 weeks of data was assigned to the 10 mg/kg IV dose group and withdrew from the study at Day 15 post-CHMI.

Tmax is the time it takes to reach Cmax of CIS43LS after it has been administered; it is determined based on the summary PK curve for each dose group.

Time frame: Baseline through 24 weeks after CIS43LS product administration

Population: Population included all enrolled participants who received CIS43LS intravenously in Part A and/or Part B of the study with up to 24 weeks of pharmacokinetic data (N=25). The 5 mg/kg SC dose group could not be evaluated due to truncated sample collections. Data in the 20 mg/kg IV dose group included 1 who received 5 mg/kg IV, 1 who received 5 mg/kg SC, and 2 who received 20 mg/kg IV in Part A of the study and received a second dose of CIS43LS at 20 mg/kg of body weight in Part B of the study.

Tmax is the time it takes to reach Cmax of CIS43LS after it has been administered; it is determined based on the summary PK curve for each dose group.

Time frame: Baseline through 24 weeks after CIS43LS product administration

Population: Population included 22 enrolled participants who received CIS43LS: 21 CIS43LS participants with 24 weeks of pharmacokinetic data and one CIS43LS participant with 8 weeks of data (N=22). The participant with 8 weeks of data was assigned to the 10 mg/kg IV dose group and withdrew from the study at Day 15 post-CHMI.