Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
M5717 · 2 trials · 2 indications
The time (in days) to first recorded parasitemia (parasite count \>0) since the first negative blood smear (parasite count of 0) after treatment (followed at least by 1 subsequent visit with a negative blood film), i.e. the time without a positive blood smear. Median time and 95% CI was estimated using the Kaplan Meier method for each cohort.
An adverse event (AE) was defined as any untoward medical occurrence in a participant. TEAEs are defined as AEs which started at or after the administration of study intervention (study treatment) or which started prior to the first administration of study intervention but worsened after the dose intake, until the last scheduled assessment will be regarded as treatment-emergent, but before established rescue antimalarial treatment is administered, if required. A serious TEAE 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. A TEAE was considered to be "related" if a causal relationship between study treatment and the TEAE is at least reasonably possible.
Number of participants with clinically significant change from baseline in laboratory parameters were reported. Clinical Significance was decided by the investigator. Laboratory investigation included hematology, biochemistry, and coagulation.
Number of participants with clinically significant change from baseline in ECG parameters were reported. Clinical Significance was decided by the investigator. The 12-lead ECGs were recorded after the participants have rested for at least 5 minutes in supine position. The parameters included heart rate (HR), Respiratory Rate, Pulse Rate, QRS, QT and QTcB calculated by the Bazett formula.
Number of participants with clinically significant change from baseline in vital signs. Clinical Significance was decided by the investigator. Vital signs included oral body temperature, systolic blood pressure, diastolic blood pressure, and pulse rate.
PCR-adjusted ACPR 28 days after first treatment (i.e., on Day 29) was defined as absence of parasitemia (thick smear/microscopy, after adjustment for parasitemia due to new infections as determined by genotyping using PCR techniques), irrespective of axillary temperature, in participants who did not previously meet any of the criteria of Early treatment failure (ETF), Late clinical failure (LCF), or Late parasitological failure (LPF).
| Arm | Type | Description |
|---|---|---|
| Cohort 1: M5717 (60 mg) + Pyronaridine | EXPERIMENTAL | Participants received single oral dose of M5717 60 milligram (mg) plus pyronaridine tetraphosphate (pyronaridine) 720 mg (Participants \>= 65 kilogram \[kg\]) or pyronaridine 540 mg (Participants \>= 45 to \< 65 kg) once daily in a single day treatment regimen. |
| Cohort 2: M5717 (200 mg) + Pyronaridine | EXPERIMENTAL | Participants received single oral dose of M5717 200 mg plus pyronaridine 720 mg (Participants \>= 65 kg) or pyronaridine 540 mg (Participants \>= 45 to \< 65 kg) once daily in a single day treatment regimen. |
| Cohort 3: M5717 (660 mg)+ Pyronaridine | EXPERIMENTAL | Participants received single oral dose of M5717 660 mg plus pyronaridine 720 mg (Participants \>= 65 kg) or pyronaridine 540 mg (Participants \>= 45 to \< 65 kg) once daily in a single day treatment regimen. |
| Cohort 4: Atovaquone-proguanil | EXPERIMENTAL | Participants received orally 3 doses of Malarone (fixed-dose combination of atovaquone-proguanil) once daily in a 3-day treatment regimen. |
| Part A: Safety Run-in Cohort M5717+Pyronaridine | EXPERIMENTAL | M5717 and pyronaridine once daily in a single day treatment regimen at low dose of 330 milligrams (mg) and 360 mg respectively. |
| Part B: Dose escalation cohort; M5717+Pyronaridine | EXPERIMENTAL | After completion of Part A, if dose will be considered safe and well tolerated, the Internal Data Monitoring Committee (IDMC) will have the option to recommend dose adjustments. M5717 and pyronaridine once daily will be administered in an escalated dose in a single day or 2-day treatment regimen. |
| Name | Type | Description |
|---|---|---|
| M5717 60 mg | DRUG | Participants received single oral dose (Capsules) of 60 mg M5717 on Day 1 under fasting condition |
| Pyronaridine | DRUG | Participants received Pyronaridine tablets orally single dose of 720 (Participants \>= 65 kg) and 540 mg (Participants \>= 45 to \< 65 kg) on Study Day 1 under fasting condition |
| Atovaquone-Proguanil | DRUG | Participants received Atovaquone-Proguanil tablets 1000/400 mg once daily in a 3-day treatment regimen. |
| M5717 200 mg | DRUG | Participants received single oral dose (Capsules) of 200 mg M5717 on Day 1 under fasting condition |
| M5717 660mg | DRUG | Participants received single oral dose (Capsules) of 660 mg M5717 on Day 1 under fasting condition |
| M5717 330 mg | DRUG | Participants will receive orally 330 mg granules of M5717 in combination with pyronaridine dispersed in water under fasting condition. |
| M5717 500 mg | DRUG | Adolescent participants with weight less than (\<) 45 kilograms (kg) will receive orally 500 mg granules of M5717 in combination with pyronaridine dispersed in water once daily under fasting condition. |
| M5717 660 mg | DRUG | Adult and adolescent participants with weight more than or equal to (\>=) 45 kg will receive orally 660 mg granules of M5717 in combination with pyronaridine dispersed in water once daily under fasting condition. |
| Pyronaridine 360 mg | DRUG | Participants will receive 360 mg of pyronaridine tablets in combination with M5717 under fasting condition. |
| Pyronaridine 540 mg | DRUG | Participants with weight \>=45 to \<65 kg will receive 540 mg of Pyronaridine tablets in combination with M5717 under fasting condition. |
| Pyronaridine 720 mg | DRUG | Participants with weight \>=65 kg will receive 720 mg of Pyronaridine tablets in combination with M5717 under fasting condition. |
Inclusion Criteria: * Participants with Asymptomatic Plasmodium falciparum Malaria with no Fever or other sign of Acute Uncomplicated Malaria and, with Microscopic confirmation using Giemsa-stained thick film, and a Parasitemia of \>= 40 to \<= 10,000 Asexual Parasites/Microliter (μL) of Blood. * A...
M5717 is an investigational small molecule being developed for the treatment and prevention of malaria. It is being studied in adults and adolescents with acute uncomplicated Plasmodium falciparum malaria and in people with asymptomatic Plasmodium falciparum infection. It is given in combination with pyronaridine.
M5717 is being developed by Merck KGaA, which trades under the ticker MKGAF. The company is running the clinical program evaluating M5717 in combination with pyronaridine for malaria indications in adults and adolescents.
M5717 is in Phase 2 clinical development. It has not been approved by the FDA and remains investigational. Two Phase 2 studies have been completed: CAPTURE 1 in acute uncomplicated malaria and CAPTURE-2 in asymptomatic infection.
M5717 has been studied in two completed Phase 2 trials. NCT05689047, also called CAPTURE 1, tested M5717 with pyronaridine in 38 adults and adolescents with acute uncomplicated Plasmodium falciparum malaria. NCT05974267, or CAPTURE-2, evaluated the combination as chemoprevention in 192 participants with asymptomatic infection.
The M5717 Phase 2 trials enrolled participants in sub-Saharan Africa. CAPTURE 1 ran in Burkina Faso, Gabon, Mozambique, and Uganda, while CAPTURE-2 ran in Burkina Faso, Kenya, The Gambia, and Zambia. Both studies enrolled participants aged 12 years and older, including both males and females.