Safety and Protective Efficacy of Intravenous Immunization With Cryopreserved Plasmodium Falciparum Sporozoites Under Chemoprophylaxis
Condition: Malaria; Plasmodium Falciparum Malaria
MeSH terms: Malaria; Malaria, Falciparum
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): PfSPZ Challenge; 0.9% Sodium Chloride (Placebo)
Intervention type(s): Biological; Biological
Intervention description(s): Aseptic, purified, vialed, cryopreserved, infectious P. falciparum sporozoites, strain NF54
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Malaria; Plasmodium falciparum malaria; Antimalarial chemoprophylaxis; PfSPZ Challenge; Cryopreserved Plasmodium Falciparum Sporozoites; PfSPZ-CVac