Phase 1
Completed N=39
Chemoprophylactic Activity of M5717 in PfSPZ Challenge Model
Healthy
Source: ClinicalTrials.gov NCT04250363 ↗
Enrolled (actual)
39
Serious AEs
0.0%
Results posted
May 2024
Primary outcomePrimary: Early Liver Stage: Number of Participants Over Time With Positive Parasitemia — 6; 3; 2; 1 Participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Early Liver Stage: Number of Participants Over Time With Positive Parasitemia |
6; 3; 2; 1; 0; 0 | — |
| PRIMARY Late Liver Stage: Number of Participants Over Time With Positive Parasitemia |
3; 0; 0; 0 | — |
| PRIMARY Early Liver Stage: Time to First Positive Parasitemia Based on Quantitative Polymerase Chain Reaction (qPCR) |
10.0; 15.0; 22.0; 24.0 | — |
| PRIMARY Late Liver Stage: Time to First Positive Parasitemia Based on Quantitative Polymerase Chain Reaction (qPCR) |
10.0 | — |
| PRIMARY Early Liver Stage: Number of Participants With Documented Blood Stage Parasite Growth |
5; 2; 2; 1; 0; 0 | — |
| PRIMARY Late Liver Stage: Number of Participants With Documented Blood Stage Parasite Growth |
3; 0; 0; 0 | — |
| PRIMARY Early Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score |
0.0; 0.3; 0.2; 0.0; 0.0; 0.1 | — |
| PRIMARY Late Liver Stage: Clinical Symptoms of Malaria Assessed Using Malaria Clinical Score |
0.0; 0.0; 0.0; 0.0; 0.0; 0.3 | — |
| PRIMARY Dose Exposure Response Relationship of M5717 Assessed by Logistic Regression Model |
1.27; 1.43; 1.44; 0.800; 2.45 | 0.00284 sig |
| SECONDARY Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-related TEAEs |
5; 3; 6; 6; 3; 3 | — |
| SECONDARY Number of Participants With Treatment Emergent Adverse Events (TEAEs) Based on Severity |
5; 3; 6; 6; 3; 3 | — |
| SECONDARY Number of Participants With Clinically Significant Change From Baseline in Laboratory Values |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Clinically Significant Change From Baseline in Vital Signs |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Area Under the Blood Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M5717 |
1280; 1990; 1890; 9840; 1100; 2330 | — |
| SECONDARY Area Under the Blood Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-tlast) of M5717 |
21.9; 852; 1270; 1470; 7330; 657 | — |
| SECONDARY Area Under the Blood Concentration-Time Curve From Time Zero to 24 Hours Post-dose (AUC 0-24) of M5717 |
25.8; 198; 280; 290; 975; 160 | — |
| SECONDARY Area Under the Blood Concentration-Time Curve From Time Zero to 168 Hours Post-dose (AUC 0-168) of M5717 |
50.4; 805; 1190; 1390; 3680; 692 | — |
| SECONDARY Maximum Observed Blood Concentration (Cmax) of M5717 |
3.56; 11.7; 16.6; 17.2; 57.2; 9.38 | — |
| SECONDARY Blood Concentration at 24 Hours (C24) of M5717 |
NA; 6.77; 9.42; 11.3; 30.6; 6.06 | — |
| SECONDARY Blood Concentration at 168 Hours (C168) of M5717 |
NA; 2.89; 4.31; 4.16; 11.4; NA | — |
| SECONDARY Time to Reach Maximum Blood Concentration (Tmax) of M5717 |
6.00; 1.00; 3.25; 6.00; 1.00; 1.00 | — |
| SECONDARY Apparent Terminal Half-life (t1/2) of M5717 |
121; 121; 66.9; 494; 94.1; 95.4 | — |
| SECONDARY Elimination Rate Constant (Lambda z) of M5717 |
0.00597; 0.00529; 0.00885; 0.00182; 0.00677; 0.00786 | — |
| SECONDARY Apparent Total Body Clearance From Blood (CL/f) of M5717 |
46.9; 40.3; 52.9; 20.3; 54.8; 43.0 | — |
| SECONDARY Apparent Volume of Distribution (Vz/F) During the Terminal Phase of M5717 |
7850; 7600; 5980; 11200; 8130; 5490 | — |
Eligibility Criteria
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 ( =] 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 or 90 or 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 exclusion criteria could apply
Data sourced from ClinicalTrials.gov (NCT04250363). 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. Informational only — not medical advice.