NCT03163121

Safety and Protective Efficacy of Genetically Attenuated PfSPZ-GA1 Vaccine in Healthy Dutch Volunteers

Safety and Protective Efficacy of Genetically Attenuated Pf∆b9∆Slarp (PfSPZ-GA1) Malaria Parasites in Healthy Dutch Volunteers

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 67 (actual)
• Sponsor: Sanaria Inc. · Industry
• Sex: All
• Age: 18 Years – 35 Years
• Healthy volunteers: Accepted

Summary

This is a first-in-human, randomized clinical trial of PfSPZ-GA1 Vaccine (genetically attenuated PfSPZ) in healthy malaria-naïve adult volunteers. This Phase 1 trial is divided into two stages, Stage A and B. Stage A is an open label, single center, dose escalation study in 19 volunteers. Stage B is a multi-center, double blind, randomized, placebo-controlled trial in 48 volunteers. The primary objective of this study is to determine the safety and tolerability of direct venous inoculation (DVI) of PfSPZ-GA1 Vaccine in healthy adults.

Detailed description

Stage A, a Phase 1 dose-escalation study, will take place at Leiden University Medical Centre (LUMC). Stage B, a randomized, double-blind, placebo-controlled trial, will be conducted at LUMC and Radboudumc University Medical Centers (RUMC). In Stage A, 19 healthy, adult volunteers will be allocated into three groups to receive increasing doses of PfSPZ-GA1 Vaccine by DVI. Group 1 (n=3) will receive one dose of 1.35 x 10\^5 PfSPZ of PfSPZ-GA1 Vaccine. If this dose is safe for 28 days after inoculation, then Group 2 (n=3) will receive one dose of 4.5 x 10\^5 PfSPZ of PfSPZ-GA1 Vaccine. If this dose is safe for 28 days after inoculation, Group 3 (n=13) will receive one dose of 9.0 x 10\^5 PfSPZ of PfSPZ-GA1 Vaccine. Volunteers will be followed closely for monitoring of adverse events and possible breakthrough blood infections by testing for the presence of parasitemia by qPCR. All volunteers will be treated with a curative regimen of atovaquone/proguanil (A/P) should break-through parasites be detected in the peripheral blood, or at the end of the follow-up period (28 days) if they are not qPCR positive. Six months after the inoculation, a final visit will take place to assess adverse events. If inoculation is deemed safe after 28 days for Group 3 and criteria for proceeding to Stage B are met, the trial will continue to Stage B. In Stage B, 48 healthy, adult volunteers will be randomized into four groups at 2 centers, LUMC and RUMC (24 volunteers at each site). Each group will receive 3 repeat doses, 8 weeks apart, of PfSPZ-GA1 Vaccine (low and high doses), PfSPZ Vaccine (radiation attenuated sporozoites), or normal saline (NS) placebo (as control) via DVI. Group 4 (n=13) will receive 9.0 x 10\^5 PfSPZ of PfSPZ-GA1 Vaccine/dose. Group 5 (n=13) will receive 4.5 x 10\^5 PfSPZ of PfSPZ-GA1 Vaccine/dose. Groups 6 (n=13) and 7 (n=9) will receive 4.5 x 10\^5 PfSPZ Vaccine and NS placebo per dose, respectively. Three weeks after the last inoculation, all immunized volunteers and placebo controls (Group 7) will undergo a CHMI with five NF54-infected mosquitoes (wild-type) to determine degree of protection. After the CHMI, volunteers will be followed closely for monitoring of adverse events and blood stage infections, and will be seen once daily from day 6 until day 21 after infection and on day 28. All volunteers will be treated with a curative regimen of antimalarials, which may be A/P or alternatively artemether/lumefantrine dosed according to Dutch clinical practice, at the time of detection of blood stage parasitemia by qPCR or 28 days after CHMI. Adverse events will be assessed up to 6 months after the CHMI.

Conditions

• Malaria

Interventions

Type	Name	Description
BIOLOGICAL	PfSPZ-GA1 Vaccine	Aseptic, purified, cryopreserved, genetically attenuated P. falciparum sporozoites (Pf∆b9∆slarp), strain NF54
BIOLOGICAL	PfSPZ Vaccine	Aseptic, purified, cryopreserved, radiation attenuated P. falciparum sporozoites (PfSPZ Vaccine), strain NF54
OTHER	Normal Saline	0.9% sodium chloride
BIOLOGICAL	Mosquito-bite CHMI	Bites of 5 infected mosquitoes of NF54 strain

Timeline

• Start date: 2017-05-12
• Primary completion: 2018-10-25
• Completion: 2018-10-25
• First posted: 2017-05-22
• Last updated: 2019-03-05

Locations

2 sites across 1 country: Netherlands

Regulatory

• FDA-regulated drug study