NCT02115516

Safety and Protective Efficacy of Intravenous Immunization With Cryopreserved Plasmodium Falciparum Sporozoites Under Chemoprophylaxis

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 67 (actual)
• Sponsor: Sanaria Inc. · Industry
• Sex: All
• Age: 18 Years – 45 Years
• Healthy volunteers: Accepted

Summary

TÜCHMI-002 is a single center, randomized, placebo-controlled, double-blinded, PfSPZ Challenge dose finding trial with two chemoprophylactic regimens and subsequent controlled human malaria infection (CHMI).

Detailed description

TÜCHMI-002 is a single center, randomized, placebo-controlled, double-blinded, PfSPZ Challenge dose finding trial with two chemoprophylactic regimens and subsequent controlled human malaria infection (CHMI), designed to establish a regimen of PfSPZ Challenge under chemoprophylaxis, with PfSPZ Challenge administered IV, that: 1. Is safe and well tolerated. 2. Provides consistent sterile protection against CHMI with homologous sporozoites in healthy adult subjects. 3. Is a practical regimen for PfSPZ Challenge chemoprophylaxis. Volunteers will receive three immunizing PfSPZ Challenge IV injections 4 weeks apart under oral chemoprophylaxis. The trial is sequential and has two stages: A) In the first stage, the PfSPZ Challenge dose is increased sequentially from 3,200 to 51,200 PfSPZ among the three groups. Controls for the three groups will receive 0.9% Sodium Chloride (NaCl) as placebo. All volunteers will receive a standard chemoprophylactic regimen of chloroquine (CQ) for 10 weeks. Briefly, 10 mg/kg CQ base will be given as loading dose followed by weekly doses of 5 mg/kg CQ base. Homologous CHMI is done with 3,200 PfSPZ Challenge IV eight weeks after the last immunizing PfSPZ Challenge injection. B) In Stage B, accelerated regimens with CQ and CQ plus ER-AZ will be assessed. Initiation of Stage B of the trial is dependent upon demonstration of at least 75% (6 out of 8) protective efficacy against homologous CHMI in Stage A, no PfSPZ Challenge related SAEs and approval by the Safety Monitoring Committee (SMC). CHMI is done with 3,200 PfSPZ Challenge (NF54) IV ten weeks after the last immunization with PfSPZ Challenge under chemoprophylaxis. Injections are either done over 28 or 10 days, chemoprophylaxis is given for 5 weeks and 15 days, respectively. Control groups will receive 0.9% NaCl IV as placebo under the respective chemoprophylactic regimen. Transition from Stage A to Stage B depends on a positive safety and efficacy review and approval by an independent SMC. Safety and efficacy data will also be submitted to the regulatory authorities (FDA in the U.S. and Paul-Ehrlich-Institute in Germany) as well as to the Ethics Committee. Sponsor, SMC and principal investigator will select PfSPZ dose after review of safety and efficacy data. In case of 100% efficacy of more than one dose regimen and comparable tolerability and safety, the higher PfSPZ dose will be used. Information about the selected dose together with the updated volunteer information document stating the dose will be submitted to the ethics committee for approval before initiation of Stage B. In case that PfSPZ Challenge related SAEs occur or efficacy of the best regimen is below 75% the study will not proceed to Stage B.

Conditions

• Malaria
• Plasmodium Falciparum Malaria

Interventions

Type	Name	Description
BIOLOGICAL	PfSPZ Challenge	Aseptic, purified, vialed, cryopreserved, infectious P. falciparum sporozoites, strain NF54
BIOLOGICAL	0.9% Sodium Chloride (Placebo)

Timeline

• Start date: 2014-04-01
• Primary completion: 2015-12-01
• Completion: 2016-04-01
• First posted: 2014-04-16
• Last updated: 2017-05-15

Locations

1 site across 1 country: Germany