Safety and Efficacy of Sanaria's PfSPZ-CVac in Malian Adults
Condition: Plasmodium Falciparum Infection
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 1

Summary: 
      Single site, double-blinded, randomized, placebo-controlled clinical trial of PfSPZ-CVac
      safety, tolerability, immunogenicity and efficacy against naturally occurring malaria in
      malaria-exposed Malian adults. The overall goal of the study is to evaluate if a regimen of
      PfSPZ-CVac (PfSPZ Challenge under chemoprophylaxis) is safe, well-tolerated, and provides
      sterile protection against naturally-occurring malaria in malaria-experienced adults. The
      study population includes 62 healthy, malaria-experienced adults aged 18-45 years, inclusive,
      residing in Bougoula Hameau and surrounding villages, Mali. The primary objective of this
      study is to assess the safety and tolerability of PfSPZ Challenge compared to placebo among
      malaria-experienced adults taking chloroquine prophylaxis (PfSPZ-CVac)
    

Detailed description: 
      This is a single site, double-blinded, randomized, placebo-controlled clinical trial of
      PfSPZ-CVac safety, tolerability, immunogenicity and efficacy against naturally occurring
      malaria in malaria-exposed Malian adults. The overall goal of the study is to evaluate if a
      regimen of PfSPZ-CVac (PfSPZ Challenge under chemoprophylaxis) is safe, well-tolerated, and
      provides sterile protection against naturally-occurring malaria in malaria-experienced
      adults. Participants will receive three immunizing PfSPZ Challenge injections via direct
      venous inoculation (DVI) four weeks apart under chloroquine chemoprophylaxis. The PfSPZ
      Challenge dose will be 204,800 PfSPZ. This is based on results of studies in Europe and in
      Africa. In Tübingen, Germany, 100% of malaria-naïve adults who received three doses of 51,200
      PfSPZ every four weeks under chloroquine chemoprophylaxis were protected against homologous
      controlled human malaria infection (CHMI). At the same time, studies of PfSPZ Vaccine in
      malaria-experienced adults in Mali and in Tanzania demonstrate that higher doses of PfSPZ are
      required to demonstrate immunogenicity and high grade protection in malaria-experienced
      adults that is comparable to that achieved in malaria-naïve adults studied in the USA. For
      this reason, the dose selected for this study is four-fold higher than the dose used for
      Tübingen, Germany. Controls will receive 0.9% sodium chloride (NaCl) as placebo. All
      participants will receive a standard chemoprophylactic regimen of chloroquine (CQ) for 10
      weeks. Chloroquine will be given as a loading dose (600mg chloroquine base) two days before
      the first administration of PfSPZ Challenge, followed by weekly doses of chloroquine (300mg
      chloroquine base weekly). Participants will also be treated with a 7-day regimen of
      artesunate (200 mg per day) after the last PfSPZ Challenge dose of 204,800 sporozoites for
      malaria parasite clearance, one week after the last CQ dose is given. A total of 62
      participants will be randomized in a 1:1 ratio to one of two groups and will be inoculated
      with PfSPZ Challenge or 0.9% NaCl by DVI so that a total of 62 adults will participate in the
      study. Participants will be recruited from the MRTC's Bougoula-Hameau site. All volunteers
      recruited will be healthy adults aged between 18 and 45 years. Safety and infectivity data
      will be collected. Volunteers, clinical and laboratory investigators will be blinded to group
      allocation. Participants will be followed every four weeks after the last vaccination as
      outpatients for active malaria diagnosis and treatment. Passive follow-up will be
      accomplished by continuous availability of study staff onsite to diagnose and treat malaria
      and other medical issues that arise. The primary objective of this study is to assess the
      safety and tolerability of PfSPZ Challenge compared to placebo among malaria-experienced
      adults taking chloroquine prophylaxis (PfSPZ-CVac). The secondary objectives are: 1. to
      assess the protective efficacy of PfSPZ-CVac against naturally transmitted P. falciparum
      malaria infection as diagnosed by thick blood smear microscopy, 2. To assess protective
      efficacy of PfSPZ-CVac against naturally transmitted P. falciparum malaria infection as
      diagnosed by qPCR, 3. to assess the expanded efficacy of PfSPZ-CVac compared to placebo, and
      4. to examine the immune response to P. falciparum malaria infection.
    

Intervention name(s): Artesunate; Chloroquine; PfSPZ (NF54) Challenge; Placebo
Intervention type(s): Drug; Drug; Biological; Other
Intervention description(s): Artesunate is a succinic ester of artemether.; 4-aminoquinolone, antimalarial agent for oral administration; Cryopreserved Plasmodium falciparum (Pf) fully infectious sporozoites (SPZ) that have been developed to be used to infect volunteers in controlled human malaria infection (CHMI) to assess the efficacy of antimalarial drugs and vaccines. The PfSPZ (NF54) Challenge contains a laboratory malaria strain isolated from a Dutch traveler to Africa.; Placebo
Intervention MeSH terms: Artesunate; Chloroquine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: Chloroquine Chemoprophylaxis; Efficacy; Immunogenicity; Malaria; Placebo; Plasmodium falciparum Sporozoites; Safety; Tolerability