Phase 1
N=88
First-in-Human Trial of Single Ascending Dose, Multiple Ascending Dose and Malaria Challenge Model in Healthy Participants
Healthy
Bottom Line
View on ClinicalTrials.gov: NCT03261401 ↗Enrolled (actual)
88
Serious AEs
0.0%
Results posted
Oct 2023
Primary outcome: Primary: Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation of Study Treatment — 13; 6; 5; 3 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- M5717 (Drug); Placebo (Drug)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- Merck KGaA, Darmstadt, Germany
- Primary completion
- Jun 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation of Study Treatment |
13; 6; 5; 3; 4; 3 | — |
| PRIMARY Part A: Number of Participants With Clinically Significant Changes From Baseline in Laboratory Assessments |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Part A: Number of Participants With Clinically Significant Changes From Baseline in 12-lead Electrocardiograms (ECGs) Findings |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Part A: Number of Participants With Clinically Significant Changes From Baseline in Vital Signs |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Part C: Parasite Reduction Ratio (PRR) Assessed Through Quantitative Polymerase Chain Reaction (qPCR) Analysis |
1.15; 1.73; 3.86; 12892; 5127; 436 | — |
| PRIMARY Part C: Maximum Observed Plasma Concentration (Cmax) of M5717 |
36.3; 174; 269 | — |
| PRIMARY Part C: Time to Reach Maximum Observed Plasma Concentration (Tmax) of M5717 |
3.75; 2.01; 2.00 | — |
| PRIMARY Part C: Terminal Elimination Rate Constant (Lambda z) of M5717 |
0.00653; 0.00476; 0.00358 | — |
| PRIMARY Part C: Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of M5717 |
3100; 10300; 20000 | — |
| PRIMARY Part C: Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of M5717 |
2680; 9470; 19200 | — |
| PRIMARY Part C: Area Under the Plasma Concentration-Time Curve From Time Zero to Time 144 Hours After Drug Administration (AUC0-144h) of M5717 |
1930; 6260; 10000 | — |
| PRIMARY Part C: Apparent Terminal Half Life (t1/2) of M5717 |
106; 146; 193 | — |
| PRIMARY Part C: Apparent Total Clearance (CL/f) of M5717 |
38.4; 31.1; 31.9 | — |
| PRIMARY Part C: Apparent Volume of Distribution During Terminal Phase (VZ/f) of M5717 |
5880; 6530; 8890 | — |
| PRIMARY Part C: Time Above or Equal to the Predicted M5717 Minimum Inhibitory Concentration (MIC) of 3 ng/mL (t =>3 ng/mL) |
314.55; 518.50; 809.12 | — |
| PRIMARY Part C: Time Above or Equal to the Predicted M5717 Minimum Parasiticidal Concentration (MPC) of 10 ng/mL (t =>10 ng/mL) |
107.47; 281.15; 500.26 | — |
| SECONDARY Part A: Maximum Observed Plasma Concentration (Cmax) of M5717 |
7.50; 14.9; 35.7; 146; 267; 642 | — |
| SECONDARY Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of M5717 |
1.00; 7.00; 4.00; 3.00; 2.00; 1.75 | — |
| SECONDARY Part A: Terminal Elimination Rate Constant (Lambda z) of M5717 |
0.00523; 0.00523; 0.00478; 0.00447; 0.00382; 0.00411 | — |
| SECONDARY Part A: Apparent Terminal Half Life (t1/2) of M5717 |
133; 133; 145; 155; 181; 169 | — |
| SECONDARY Part A: Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of M5717 |
997; 1710; 3500; 10100; 17500; 28600 | — |
| SECONDARY Part A: Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of M5717 |
492; 1250; 2630; 9290; 15800; 27900 | — |
| SECONDARY Part A: Area Under the Plasma Concentration-Time Curve From Time Zero to Time 144 Hours After Drug Administration (AUC0-144h) of M5717 |
475; 949; 1940; 5830; 9510; 18400 | — |
| SECONDARY Part A: Extrapolated Area Under the Plasma Concentration Curve From Time of Last Quantifiable Sample to Infinity (AUCextra%) of M5717 |
45.2; 26.2; 24.0; 6.98; 5.89; 2.36 | — |
| SECONDARY Part A: Apparent Total Clearance (CL/f) of M5717 |
39.9; 46.5; 45.5; 31.7; 27.4; 27.9 | — |
| SECONDARY Part A: Apparent Volume of Distribution During Terminal Phase (VZ/f) of M5717 |
7640; 8890; 9510; 7100; 7160; 6770 | — |
| SECONDARY Part A: Dose Normalized AUC0-inf [AUC(0-inf/Dose)] of M5717 |
25.1; 21.5; 22.0; 31.5; 36.5; 35.9 | — |
| SECONDARY Part A: Dose Normalized AUC0-144h [AUC(0-144hour/Dose)] of M5717 |
11.9; 11.9; 12.2; 18.3; 19.9; 23.1 | — |
| SECONDARY Part A: Dose Normalized AUC0-t [AUC( 0-t/Dose)] of M5717 |
12.4; 15.7; 16.5; 29.1; 33.1; 35.0 | — |
| SECONDARY Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax/Dose) of M5717 |
0.189; 0.187; 0.224; 0.459; 0.559; 0.805 | — |
| SECONDARY Part A: Time Above or Equal to the Predicted M5717 Minimum Inhibitory Concentration (MIC) of 3 ng/mL (t =>3 ng/mL) |
84.97; 190.36; 318.49; 551.05; 765.01; 868.99 | — |
| SECONDARY Part A: Time Above or Equal to the Predicted M5717 Minimum Parasiticidal Concentration (MPC) of 10 ng/mL (t=>10 ng/mL) |
0.00; 12.43; 88.02; 272.00; 436.47; 506.34 | — |
| SECONDARY Part C: Parasite Clearance Time |
35.8; 54.4; 55.7 | — |
| SECONDARY Part C: Parasite Clearance Half-life (PCT 1/2) |
231.06; 60.42; 24.66; 3.52; 3.89; 5.47 | — |
| SECONDARY Part C: Number of Participants With Lag Phase |
0; 6; 0; 3; 0; 7 | — |
| SECONDARY Part C: Number of Participants With Recrudescence |
3; 2; 0 | — |
| SECONDARY Part C: Malarial Clinical Score |
0; 0; 1; 0; 1; 0 | — |
| SECONDARY Part C: Minimum Inhibitory Concentration (MIC) and Minimum Parasiticidal Concentration at 90% (MPC90) |
7.59; 7.59; 7.59; 9.21; 9.21; 9.21 | — |
| SECONDARY Part C: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation of Study Treatment |
6; 8; 7; 0; 0; 0 | — |
| SECONDARY Part C: Number of Participants With Clinically Significant Changes From Baseline in Laboratory Assessments |
0; 0; 0 | — |
| SECONDARY Part C: Number of Participants With Clinically Significant Changes From Baseline in 12-lead Electrocardiograms (ECGs) Findings |
0; 1; 1 | — |
| SECONDARY Part C: Number of Participants With Clinically Significant Changes From Baseline in Vital Signs |
0; 0; 0 | — |
Summary
The primary purpose of this study was to investigate the safety and tolerability of M5717 and to characterize the Pharmacokinetics (PK) /Pharmacodynamic relationship between M5717 PK and parasite clearance in healthy participants following infection with Plasmodium falciparum.
Eligibility Criteria
Inclusion Criteria
- Adult men and women of non-childbearing potential, with total body weight greater than or equal to 50.0 kilogram and body mass index (BMI) between 19.0 kilogram per meter square(kg/m^2) and 29.9 kg/m^2.
- Healthy as assessed by the Investigator with 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 trial evaluation, procedures, or completion.
- Other protocol defined inclusion criteria could apply.
Exclusion Criteria
- Participants with history or presence of clinically relevant respiratory, gastrointestinal, renal, hepatic, hematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological dermatological, connective tissue diseases or disorders.
- Participants with history of relevant drug hypersensitivity, ascertained or presumptive allergy/hypersensitivity to the active drug substance and/or formulation ingredients; history of serious allergic reactions leading to hospitalization or any other allergic reaction in general, which the Investigator considers may affect the safety of the participant and/or outcome of the trial.
- Participants who have any history of malaria.
- Participants who have participated in a previous malaria vaccine trial.
- Participants who have participated in a previous human malaria challenge trial.
Data sourced from ClinicalTrials.gov (NCT03261401). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.