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of the P falciparum parasite
Image by Mae Melvin/CDC
A novel compound could be effective against malaria infections that are resistant to currently available antimalarial drugs, according to researchers.
In a phase 2 study, the compound, KAF156, proved active against Plasmodium vivax and Plasmodium falciparum malaria.
KAF156 was able to clear both blood and liver stages of malaria parasites, including artemisinin-resistant parasites.
Most of the patients in this study had at least 1 adverse event (AE). However, most were grade 1, and there were no grade 4 or serious AEs.
Results from this study were published in NEJM. The trial was funded, in part, by Novartis, the company developing KAF156.
KAF156 is the first compound from a novel class of drugs called imidazolopiperazines. The drugs’ mechanism of action is still being characterized, but it may be related to a previously uncharacterized gene—Plasmodium falciparum cyclic amine resistance locus (Pfcarl).
From March to August 2013, researchers conducted a phase 2 trial of KAF156 at 5 centers in Thailand and Vietnam.
Twenty-one of the patients in this study had acute, uncomplicated malaria—11 with P vivax and 10 with P falciparum malaria. They received multiple doses of KAF156—400 mg once daily for 3 days.
Twenty-two of the patients studied had uncomplicated, P falciparum malaria and received a single dose of KAF156 at 800 mg.
All patients were assessed for fever and parasite clearance as well as AEs. Patients in the single-dose cohort were also followed for 28 days to assess the cure rate.
Two patients were excluded from the efficacy analysis. One was a P vivax patient receiving the 400 mg dose who turned out to have a mixed infection. And the other was a P falciparum patient who vomited repeatedly after receiving 800 mg of KAF156 (after 3 attempts at dosing).
Efficacy
In the multiple-dose cohorts, the median time to fever clearance after receiving KAF156 was 14 hours (range, 4 to 30) in patients with P vivax malaria and 6 hours (range, 4 to 24) in patients with P falciparum malaria. In the single-dose cohort, the median time to fever clearance was 4 hours (range, 4 to 66).
In the multiple-dose cohorts, the median time to parasite clearance was 24 hours (range, 16 to 36) in patients with P vivax and 45 hours (range, 36 to 66) in patients with P falciparum.
In the single-dose cohort, the median time to parasite clearance was 49 hours (range, 16 to 68). One of these patients had parasite clearance at 66 hours but an asymptomatic recurrence at 84 hours. In all of the other patients, parasitemia cleared.
During follow-up of the single-dose cohort, 1 patient had reinfection, and 7 had recrudescent infections.
Safety
Most patients had at least 1 AE, although none were serious. Seventy-two percent of patients had grade 1 AEs, 35% had grade 2 AEs, and 14% had grade 3 AEs.
Sixty percent of AEs were considered related to treatment. In the multiple-dose cohorts, 14 of the 31 AEs (45%) reported in 7 patients (1 with P vivax and 6 with P falciparum malaria) were considered drug-related. All 22 P falciparum patients in the single-dose cohort had at least 1 AE that was considered drug-related.
The most common AEs were sinus bradycardia, thrombocytopenia, hypokalemia, anemia, and hyperbilirubinemia.
Two patients experienced vomiting of grade 2 or higher. One of these patients discontinued treatment because of repeated vomiting after the 800 mg dose (mentioned above). 
of the P falciparum parasite
Image by Mae Melvin/CDC
A novel compound could be effective against malaria infections that are resistant to currently available antimalarial drugs, according to researchers.
In a phase 2 study, the compound, KAF156, proved active against Plasmodium vivax and Plasmodium falciparum malaria.
KAF156 was able to clear both blood and liver stages of malaria parasites, including artemisinin-resistant parasites.
Most of the patients in this study had at least 1 adverse event (AE). However, most were grade 1, and there were no grade 4 or serious AEs.
Results from this study were published in NEJM. The trial was funded, in part, by Novartis, the company developing KAF156.
KAF156 is the first compound from a novel class of drugs called imidazolopiperazines. The drugs’ mechanism of action is still being characterized, but it may be related to a previously uncharacterized gene—Plasmodium falciparum cyclic amine resistance locus (Pfcarl).
From March to August 2013, researchers conducted a phase 2 trial of KAF156 at 5 centers in Thailand and Vietnam.
Twenty-one of the patients in this study had acute, uncomplicated malaria—11 with P vivax and 10 with P falciparum malaria. They received multiple doses of KAF156—400 mg once daily for 3 days.
Twenty-two of the patients studied had uncomplicated, P falciparum malaria and received a single dose of KAF156 at 800 mg.
All patients were assessed for fever and parasite clearance as well as AEs. Patients in the single-dose cohort were also followed for 28 days to assess the cure rate.
Two patients were excluded from the efficacy analysis. One was a P vivax patient receiving the 400 mg dose who turned out to have a mixed infection. And the other was a P falciparum patient who vomited repeatedly after receiving 800 mg of KAF156 (after 3 attempts at dosing).
Efficacy
In the multiple-dose cohorts, the median time to fever clearance after receiving KAF156 was 14 hours (range, 4 to 30) in patients with P vivax malaria and 6 hours (range, 4 to 24) in patients with P falciparum malaria. In the single-dose cohort, the median time to fever clearance was 4 hours (range, 4 to 66).
In the multiple-dose cohorts, the median time to parasite clearance was 24 hours (range, 16 to 36) in patients with P vivax and 45 hours (range, 36 to 66) in patients with P falciparum.
In the single-dose cohort, the median time to parasite clearance was 49 hours (range, 16 to 68). One of these patients had parasite clearance at 66 hours but an asymptomatic recurrence at 84 hours. In all of the other patients, parasitemia cleared.
During follow-up of the single-dose cohort, 1 patient had reinfection, and 7 had recrudescent infections.
Safety
Most patients had at least 1 AE, although none were serious. Seventy-two percent of patients had grade 1 AEs, 35% had grade 2 AEs, and 14% had grade 3 AEs.
Sixty percent of AEs were considered related to treatment. In the multiple-dose cohorts, 14 of the 31 AEs (45%) reported in 7 patients (1 with P vivax and 6 with P falciparum malaria) were considered drug-related. All 22 P falciparum patients in the single-dose cohort had at least 1 AE that was considered drug-related.
The most common AEs were sinus bradycardia, thrombocytopenia, hypokalemia, anemia, and hyperbilirubinemia.
Two patients experienced vomiting of grade 2 or higher. One of these patients discontinued treatment because of repeated vomiting after the 800 mg dose (mentioned above).
of the P falciparum parasite
Image by Mae Melvin/CDC
A novel compound could be effective against malaria infections that are resistant to currently available antimalarial drugs, according to researchers.
In a phase 2 study, the compound, KAF156, proved active against Plasmodium vivax and Plasmodium falciparum malaria.
KAF156 was able to clear both blood and liver stages of malaria parasites, including artemisinin-resistant parasites.
Most of the patients in this study had at least 1 adverse event (AE). However, most were grade 1, and there were no grade 4 or serious AEs.
Results from this study were published in NEJM. The trial was funded, in part, by Novartis, the company developing KAF156.
KAF156 is the first compound from a novel class of drugs called imidazolopiperazines. The drugs’ mechanism of action is still being characterized, but it may be related to a previously uncharacterized gene—Plasmodium falciparum cyclic amine resistance locus (Pfcarl).
From March to August 2013, researchers conducted a phase 2 trial of KAF156 at 5 centers in Thailand and Vietnam.
Twenty-one of the patients in this study had acute, uncomplicated malaria—11 with P vivax and 10 with P falciparum malaria. They received multiple doses of KAF156—400 mg once daily for 3 days.
Twenty-two of the patients studied had uncomplicated, P falciparum malaria and received a single dose of KAF156 at 800 mg.
All patients were assessed for fever and parasite clearance as well as AEs. Patients in the single-dose cohort were also followed for 28 days to assess the cure rate.
Two patients were excluded from the efficacy analysis. One was a P vivax patient receiving the 400 mg dose who turned out to have a mixed infection. And the other was a P falciparum patient who vomited repeatedly after receiving 800 mg of KAF156 (after 3 attempts at dosing).
Efficacy
In the multiple-dose cohorts, the median time to fever clearance after receiving KAF156 was 14 hours (range, 4 to 30) in patients with P vivax malaria and 6 hours (range, 4 to 24) in patients with P falciparum malaria. In the single-dose cohort, the median time to fever clearance was 4 hours (range, 4 to 66).
In the multiple-dose cohorts, the median time to parasite clearance was 24 hours (range, 16 to 36) in patients with P vivax and 45 hours (range, 36 to 66) in patients with P falciparum.
In the single-dose cohort, the median time to parasite clearance was 49 hours (range, 16 to 68). One of these patients had parasite clearance at 66 hours but an asymptomatic recurrence at 84 hours. In all of the other patients, parasitemia cleared.
During follow-up of the single-dose cohort, 1 patient had reinfection, and 7 had recrudescent infections.
Safety
Most patients had at least 1 AE, although none were serious. Seventy-two percent of patients had grade 1 AEs, 35% had grade 2 AEs, and 14% had grade 3 AEs.
Sixty percent of AEs were considered related to treatment. In the multiple-dose cohorts, 14 of the 31 AEs (45%) reported in 7 patients (1 with P vivax and 6 with P falciparum malaria) were considered drug-related. All 22 P falciparum patients in the single-dose cohort had at least 1 AE that was considered drug-related.
The most common AEs were sinus bradycardia, thrombocytopenia, hypokalemia, anemia, and hyperbilirubinemia.
Two patients experienced vomiting of grade 2 or higher. One of these patients discontinued treatment because of repeated vomiting after the 800 mg dose (mentioned above).