A Clinical Trial of the PfSPZ Vaccine Administered by Direct Venous Inoculation in Healthy Malaria-Naïve Adults: Heterologous vs. Homologous Controlled Human Malaria Infection and Reduction in Number of Doses

NCT02215707 | Completed Phase 1 DMC

• 2 other identifiers: WRAIR #2080NMRC.2014.004
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label evaluation of the safety, tolerability immunogenicity and efficacy of the PfSPZ Vaccine administered by Direct Venous Inoculation (DVI) in healthy, malaria-naïve subjects. There will be 3 groups and a total of 69 subjects (45 immunized subjects and 24 infectivity controls).

Conditions

Malaria

Keywords

PfSPZ Vaccine; Plasmodium falciparum; Malaria; Controlled Human Malaria Infection (CHMI)

Outcome Measures

Primary Outcomes (2)

• Incidence and type of adverse events (including breakthrough infections), vital signs, clinical laboratory assessments, physical examination findings.

  Day of immunization through week 52

• Evidence of vaccine-mediated protection against CHMI 2-3 weeks and 24 weeks after last immunization in Groups 1, 2, and 3, preventing blood stage infection for 28 days (as detected by blood smear analysis) following CHMI.

  28 days post each CHMI

Secondary Outcomes (10)

• Antibody titers to Pf proteins by ELISA

  Screening until week 52

• Antibody titers to Pf parasite stages by IFA

  Screening until week 52

• Capacity to inhibit sporozoite invasion of hepatocytes in vitro by ISI assay

  Screening until week 52

• Analysis of antibodies to any of the thousands of proteins in the Pf proteome using proteome array chips

  Screening until week 52

• Multi-channel intracellular staining (ICS) analysis by flow cytometry against PfSPZ and synthetic peptides and recombinant proteins from defined Pf proteins

  Screening until week 52

Study Arms (7)

Group 1

EXPERIMENTAL

Group 1: 5 doses of 2.7x10\^5 PfSPZ Vaccine; homologous 3D7 CHMI Grp 1 (n=15) gets 5 doses of 270,000 PfSPZ per dose (4 doses at 4 wk intervals, 2 month delay before 5th dose) by DVI. Grps 1 and 2 start immunizations together. 1 subj in each of Grps 1 and 2 will be immunized approx 24 hrs before rest of grp ("pilot subjects"). For Grp1/Grp 2 pilot subjects: 1st subject will be immunized, observed on site for minimum 1 hr; the 2nd subject may be immunized, will also be observed for minimum 1 hr. If no safety concerns are identified after 24 hrs that trigger the stopping rules, then rest of subjects in Grps 1 and 2 will be immunized. Approx 3 wks after final dose, Grps 1 and 3 will undergo homologous CHMI (Pf3D7 strain) with 6 Infectivity Controls. Approx 24 wks after last dose, Grps 1 and 3 will undergo 2nd homologous CHMI (3D7) with 6 Infectivity Controls. Subjects will be followed for 8 wks after last CHMI for safety purposes.

Biological: PfSPZ Vaccine

Group 2

EXPERIMENTAL

Grp 2: 5 doses of 2.7x10\^5 PfSPZ Vaccine; heterologous 7G8 CHMI Grp 2 (n=15) gets 5 doses of 270,000 PfSPZ/dose (4 doses at 4wk intervals, 2 month delay before 5th dose) by DVI. Grps 1 / 2 start immunizations together. 1 subj in each of Grps 1 / 2 will be immunized approx 24 hrs before rest of grp ("pilot subjects"). For Grp1/ 2 pilot subj: 1st subj will be immunized, observed on site for min 1 hr; 2nd subj may be immunized, will also be observed for min 1 hr. If no safety concerns after 24 hrs that trigger stopping rules, then rest of Grps 1 / 2 will be immunized. Approx 3 wks after final dose, Grps 1/3 have homologous CHMI; 2-3 days later, Grp 2 will undergo heterologous CHMI (Pf7G8) with 6 Infectivity Controls. Approx 24 wks after last dose, Grps 1/3 have 2nd homologous CHMI; 2-3 days later, Grp 2 will undergo 2nd heterologous CHMI (7G8 strain) with 6 Infectivity Controls. Subj will be followed for 8 wks after last CHMI for safety purposes.

Biological: PfSPZ Vaccine

Group 3

EXPERIMENTAL

Grp 3 (n=15) will receive 3 doses by DVI of 450,000 PfSPZ/dose (of PfSPZ Vaccine) at 8 wk intervals (starting approx. 4 wks after Grps 1 and 2 get 1st immunization). 3 subjects in Grp 3 will be immunized approx 24 hrs prior to rest of grp ("pilot subjects"). The 3 subjects will be immunized sequentially with min 2 hr observation period between subjects (and a 2 hr observation of 3rd subject as well). If no safety concerns identified in pilot subjects after 24 hours that trigger the stopping rules, the rest of subjects in Grp 3 will be immunized as scheduled. Approx 3 wks after final dose, Grps 1 and 3 will undergo homologous CHMI (3D7 strain) with 6 Infectivity Controls. Approx 24 wks after last dose, Grps 1 and 3 will undergo 2nd homologous CHMI (3D7) with 6 Infectivity Controls. Subjects will be followed for 8 wks after last CHMI for safety purposes.

Biological: PfSPZ Vaccine

CHMI Controls.1

NO INTERVENTION

n = 6, infectivity controls for 1st homologous CHMI (3D7) occurring approximately 3 weeks after final immunization of Groups 1 and 3. This group does not receive the PfSPZ Vaccine.

CHMI Controls.2

NO INTERVENTION

n = 6, infectivity controls for 1st heterologous CHMI (7G8) occurring approximately 3 weeks after final immunization of Group 2. This group does not receive the PfSPZ Vaccine.

CHMI Controls.3

NO INTERVENTION

n = 6, infectivity controls for 2nd homologous CHMI (3D7) occurring approximately 24 weeks after final immunization of Groups 1 and 3. This group does not receive the PfSPZ Vaccine.

CHMI Controls.4

NO INTERVENTION

n = 6, infectivity controls for 2nd heterologous CHMI (7G8) occurring approximately 24 weeks after final immunization of Group 2. This group does not receive the PfSPZ Vaccine.

Interventions

PfSPZ Vaccine BIOLOGICAL

Suspension of metabolically active, non-replicating (live), radiation-attenuated, purified, cryopreserved, aseptic Plasmodium falciparum (Pf) sporozoites (SPZ)

Group 1; Group 2; Group 3

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adults (male or non-pregnant female) 18 - 45 years of age, inclusive.
• Able and willing to participate for the duration of the study.
• Able and willing to provide written (not proxy) informed consent.
• Women of childbearing potential must agree to use effective means of birth control (e.g. oral or implanted contraceptives, IUD, female condom, diaphragm with spermicide, cervical cap, abstinence, use of a condom by the sexual partner or sterile sexual partner) during the entire study. Women with a history of surgical or chemical sterilization (e.g. tubal ligation, hysterectomy, other) must provide written documentation of infertility from a Primary Care Provider.
• Willing to refrain from blood donation (except as required in this study) for 3 years following CHMI.
• Agree not to travel to a malaria endemic region during the entire course of the trial.

You may not qualify if:

• Any history of malaria infection, or travel to a malaria endemic region within 6 months prior to first immunization.
• History of long-term residence (\>5 years) in area known to have significant transmission of P. falciparum.
• Has evidence of increased cardiovascular disease risk (defined as \> 10%, 5 year risk) as determined by the method of Gaziano \[Gaziano, 2008\]. Risk factors include sex, age, systolic blood pressure (mm Hg), smoking status, body mass index (BMI, kg/mm2), and reported diabetes status.
• Positive HIV, HBsAg or HCV serology.
• Positive sickle cell screening test.
• An abnormal electrocardiogram, defined as one showing pathologic Q waves and significant ST-T wave changes; left ventricular hypertrophy; any non-sinus rhythm including isolated premature ventricular contractions, but excluding isolated premature atrial contractions; right or left bundle branch block; or advanced (secondary or tertiary) A-V heart block.
• Current use of systemic immunosuppressant pharmacotherapy.
• Current significant medical condition (cardiovascular, hepatic, renal, or hematological) or evidence of any other serious underlying medical condition identified by medical history, physical examination, or laboratory examination.
• History of a splenectomy.
• History of neurologic disorder (including seizures) or migraine headache.
• History of psychiatric disorders (such as personality disorders, anxiety disorders, or schizophrenia) or behavioral tendencies (including active alcohol or drug abuse) discovered during the screening process that in the opinion of the investigator would make compliance with the protocol difficult.
• Plan for surgery between enrollment and CHMI.
• Females who are pregnant or nursing, females who plan on becoming pregnant or plan to nurse during the study period.
• Known allergy to any component of the vaccine formulation, history of anaphylactic response to mosquito-bites, or any history of anaphylactic reaction, retinal or visual field changes, or known allergy to anti-malarials including chloroquine phosphate, atovaquone/proguanil (Malarone®), or artemether/lumefantrine (Coartem®)
• Receipt of another investigational vaccine or drug within 30 days prior to the first immunization, or plan to participate in another investigational vaccine/drug research during or within 1 month following participation in this study.

Sponsors & Collaborators

• Sanaria Inc.: lead
• Naval Medical Research Center: collaborator
• Walter Reed Army Institute of Research (WRAIR): collaborator
• Military Infectious Diseases Research Program (MIDRP): collaborator

Study Sites (1)

Walter Reed Army Institute of Research (WRAIR) Clinical Trials Center

Silver Spring, Maryland, 20910, United States

Location

Related Publications (1)

• Epstein JE, Paolino KM, Richie TL, Sedegah M, Singer A, Ruben AJ, Chakravarty S, Stafford A, Ruck RC, Eappen AG, Li T, Billingsley PF, Manoj A, Silva JC, Moser K, Nielsen R, Tosh D, Cicatelli S, Ganeshan H, Case J, Padilla D, Davidson S, Garver L, Saverino E, Murshedkar T, Gunasekera A, Twomey PS, Reyes S, Moon JE, James ER, Kc N, Li M, Abot E, Belmonte A, Hauns K, Belmonte M, Huang J, Vasquez C, Remich S, Carrington M, Abebe Y, Tillman A, Hickey B, Regules J, Villasante E, Sim BKL, Hoffman SL. Protection against Plasmodium falciparum malaria by PfSPZ Vaccine. JCI Insight. 2017 Jan 12;2(1):e89154. doi: 10.1172/jci.insight.89154.

  PMID: 28097230 RESULT

MeSH Terms

Conditions

Malaria; Malaria, Falciparum

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• Judith Epstein, MD

  Naval Medical Research Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 1, 2014
• First Posted: August 13, 2014
• Study Start: June 1, 2014
• Primary Completion: April 1, 2015
• Study Completion: June 1, 2015
• Last Updated: June 29, 2018

Record last verified: 2015-11

Locations

US (1)