Date: 2017-05-12
Type of
information: Presentation of results at a congress
phase: 3
Announcement: presentation of results at the International Conference on Plasmodium vivax Research (ICPVR)
Company: GSK (UK) Medicines for Malaria Venture (MMV)
Product: tafenoquine
Action
mechanism:
- Tafenoquine is an investigational 8-aminoquinoline derivative with activity against the P. vivax lifecycle, including the form that lies dormant in the liver. Tafenoquine was first discovered by scientists at the Walter Reed Army Institute of Research in 1978 and is being developed in collaboration with GSK and MMV.
Disease: malaria
Therapeutic
area: Infectious diseases - Parasitic diseases
Country:
Trial
details:
- The phase III programme includes two randomised, double-blind treatment studies to investigate tafenoquine in adult patients with P. vivax malaria. The “DETECTIVE” study (TAF112582) aims to evaluate the efficacy, safety and tolerability of tafenoquine as a radical cure for P. vivax malaria, co-administered with chloroquine, a blood stage anti-malarial treatment. The “GATHER” study (TAF116564) aims to assess the incidence of hemolysis and safety and efficacy of tafenoquine compared to primaquine, the only approved treatment currently available for the radical cure of P. vivax malaria.
Latest
news:
- • On June 12, 2017, GSK and Medicines for Malaria Venture (MMV) announced positive results from two phase III studies of tafenoquine, an investigational 8-aminoquinoline, for the prevention of relapse of Plasmodium vivax (P.vivax) malaria.
- The headline results, presented at the International Conference on Plasmodium vivax Research (ICPVR) in Manaus, Brazil, show that a single-dose of 300mg tafenoquine, when given with a 3-day blood-stage chloroquine treatment, reduced the risk of relapse in patients with P.vivax malaria significantly more than placebo when given with chloroquine.
- The two phase III randomised, double-blind studies, “DETECTIVE” and “GATHER”, were conducted in malaria-endemic countries covering South America, Asia, and Africa.
- DETECTIVE (TAF112582): This was a double-blind, double-dummy phase III study evaluating the efficacy, safety and tolerability of tafenoquine in 522 patients with P.vivax malaria. Patients were randomised to receive either a single-dose (1-day) of tafenoquine (300mg), a 14-day course of primaquine (15mg), or placebo, with all patients also receiving a 3-day course of chloroquine to treat the acute blood stage of the infection. The study met its primary endpoint, showing that a statistically significant greater proportion of patients treated with tafenoquine (60%) remained relapse-free over the 6-month follow-up period than patients on placebo (26%), with an odds ratio for risk of relapse vs placebo given with chloroquine of 0.24, p<0.001.5
- Further, a statistically significant greater proportion of patients treated with 14-days of primaquine (64%) were relapse-free over the 6-month follow-up period than patients on placebo (26%), with an odds ratio vs. placebo when given with chloroquine of 0.20, p<0.001.
- The frequency of adverse events was 63% for the tafenoquine group, 59% for the primaquine group and 65% for the chloroquine group, and the frequency of serious adverse events was 8% for the tafenoquine group, 3% for the primaquine group and 5% for the chloroquine group.
- GATHER (TAF116564): This was a study in 251 patients investigating a single-dose of 300mg tafenoquine on levels of haemoglobin (a protein in red blood cells that carries oxygen) when compared to a 14-day course of 15mg primaquine, with all patients also receiving a standard
3-day course of chloroquine. The incidence of decline in haemoglobin (the primary endpoint) was very low and similar between the two treatment groups (2.4% for patients receiving tafenoquine and chloroquine vs. 1.2% for patients receiving primaquine with chloroquine), with the difference in proportions (95% CI) of 1.23% (-4.16%, 4.98%). No patient required a blood transfusion.
- The frequency of adverse events was 72% for the tafenoquine group and 75% for the primaquine group and the frequency of serious adverse events was 4% for the tafenoquine group and 1% for the primaquine group.
- Adverse events from the headline data from both studies were consistent with the known safety profile of tafenoquine. The proportion of patients experiencing adverse events and serious adverse events during the 6-month study was similar for tafenoquine, primaquine and chloroquine alone.
- GSK plans to progress regulatory filings for the prevention of relapse of P. vivax malaria later in 2017. Full results from both studies will be submitted for publication in peer-reviewed journals.
- • On April 28, 2014, GSK and Medicines for Malaria Venture (MMV) have announced the start of a phase III global programme to evaluate the efficacy and safety of tafenoquine, an investigational medicine which is being developed for the treatment and relapse prevention (radical cure) of Plasmodium vivax (P. vivax) malaria. The phase III programme includes two randomised, double-blind treatment studies to investigate tafenoquine in adult patients with P. vivax malaria. The “DETECTIVE” study (TAF112582) aims to evaluate the efficacy, safety and tolerability of tafenoquine as a radical cure for P. vivax malaria, co-administered with chloroquine, a blood stage anti-malarial treatment. The “GATHER” study (TAF116564) aims to assess the incidence of hemolysis and safety and efficacy of tafenoquine compared to primaquine, the only approved treatment currently available for the radical cure of P. vivax malaria.
- The clinical programme investigates a single dose of tafenoquine, as part of a 3-day treatment course with chloroquine, in patients with P. vivax malaria. Tafenoquine was granted Breakthrough Therapy designation by the FDA in December 2013.
Is
general: Yes
