Regimen Optimization Trial of PfSPZ Vaccine in Equatorial Guinea

NCT03590340 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: EGSPZV3
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 1, randomized regimen optimization study of PfSPZ Vaccine in healthy Equatoguinean volunteers to determine if a condensed, rapid immunization regimen is safe and efficacious. Four different regimens 4 weeks or less in duration will be evaluated for safety, tolerability, immunogenicity, and protective efficacy in comparison to a gold standard 16-week regimen.

Conditions

Malaria

Keywords

Plasmodium falciparum; PfSPZ Vaccine; PfSPZ Challenge (NF54); CHMI

Outcome Measures

Primary Outcomes (1)

• Incidence and type of Adverse Events (AEs)

  1. Occurrence of solicited local AEs during priming vaccination and a 3-day surveillance period after priming and boost vaccinations. 2. Occurrence of solicited systemic AEs during priming vaccination and a 7-day surveillance period after priming and boost vaccinations. 3. Occurrence of unsolicited AEs during priming vaccination and a 14-day surveillance period after priming and boost vaccinations. 4. Occurrence of serious adverse events (SAEs) during the study.

  Day of first immunization until 1 year

Secondary Outcomes (3)

• Proportion of volunteers who become parasitemic will be recorded, detected by thick blood smear microscopy (TBS) and/ or quantitative real time polymerase chain reaction (qPCR)

  Post first immunization uptil 56 days post-CHMI

• Level of Antibodies against Pf proteins in volunteer sera

  Post first immunization uptil 56 days post-CHMI

• Inhibitory Capacity of Volunteer Sera against in vitro Sporozoite Invasion of Hepatocytes

  Post first immunization uptil 56 days post-CHMI

Study Arms (8)

Group 1a (PfSPZ Vaccine)

EXPERIMENTAL

Group 1a: subjects (n=21) will receive four doses of PfSPZ Vaccine (9.0 x 10\^5 PfSPZ/dose) on Days 1, 3, 5, and 7 as a prime, followed by a boost of 9.0x10\^5 PfSPZ Vaccine on Day 113. Controlled human malaria infection (CHMI) with PfSPZ Challenge (NF54) will be administered 8 weeks after the last boost dose by DVI injection.

Biological: PfSPZ Vaccine; Biological: PfSPZ Challenge (for CHMI)

Group 2a (PfSPZ Vaccine)

EXPERIMENTAL

Group 2a: subjects (n=21) will receive four doses of PfSPZ Vaccine (9.0 x 10\^5 PfSPZ/dose) on Days 1, 3, 5, and 7 as a prime. CHMI with PfSPZ Challenge (NF54) will be administered 8 weeks after the last prime dose by DVI injection.

Biological: PfSPZ Vaccine; Biological: PfSPZ Challenge (for CHMI)

Group 3a (PfSPZ Vaccine)

EXPERIMENTAL

Group 3a: subjects (n=21) will receive four doses of PfSPZ Vaccine (9.0 x 10\^5 PfSPZ/dose) on Days 1, 3, 5, and 7 as a prime, followed by a boost of 9.0x10\^5 PfSPZ Vaccine on Day 29. CHMI with PfSPZ Challenge (NF54) will be administered 8 weeks after the last boost dose by DVI injection.

Biological: PfSPZ Vaccine; Biological: PfSPZ Challenge (for CHMI)

Group 4a (PfSPZ Vaccine)

EXPERIMENTAL

Group 4a: subjects (n=21) will receive two doses of PfSPZ Vaccine (9.0 x 10\^5 PfSPZ/dose) on Days 1 and 8 as a prime, followed by a boost of 9.0x10\^5 PfSPZ Vaccine on Day 29. CHMI with PfSPZ Challenge (NF54) will be administered 8 weeks after the last boost dose by DVI injection.

Biological: PfSPZ Vaccine; Biological: PfSPZ Challenge (for CHMI)

Group 1b (NS)

PLACEBO COMPARATOR

Group 1b: subjects (n=5) will receive normal saline (NS) placebo on Days 1, 3, 5, 7, and 113. CHMI with PfSPZ Challenge (NF54) will be administered 8 weeks after the last immunization by DVI.

Other: Normal saline; Biological: PfSPZ Challenge (for CHMI)

Group 2b (NS)

PLACEBO COMPARATOR

Group 2b: subjects (n=5) will receive NS placebo on Days 1, 3, 5, and 7. CHMI with PfSPZ Challenge (NF54) will be administered 8 weeks after the last immunization by DVI.

Other: Normal saline; Biological: PfSPZ Challenge (for CHMI)

Group 3b (NS)

PLACEBO COMPARATOR

Group 3b: subjects (n=5) will receive NS placebo on Days 1, 3, 5, 7, and 29. CHMI with PfSPZ Challenge (NF54) will be administered 8 weeks after the last immunization by DVI.

Other: Normal saline; Biological: PfSPZ Challenge (for CHMI)

Group 4b (NS)

PLACEBO COMPARATOR

Group 4b: subjects (n=5) will receive NS placebo on Days 1 and 8. CHMI with PfSPZ Challenge (NF54) will be administered 8 weeks after the last immunization by DVI.

Other: Normal saline; Biological: PfSPZ Challenge (for CHMI)

Interventions

PfSPZ Vaccine BIOLOGICAL

Metabolically active, non-replicating, radiation attenuated, aseptic, purified, cryopreserved NF54 P. falciparum (Pf) sporozoites (PfSPZ Vaccine)

Group 1a (PfSPZ Vaccine); Group 2a (PfSPZ Vaccine); Group 3a (PfSPZ Vaccine); Group 4a (PfSPZ Vaccine)

Normal saline OTHER

Normal saline is 0.9% sodium chloride

Group 1b (NS); Group 2b (NS); Group 3b (NS); Group 4b (NS)

PfSPZ Challenge (for CHMI) BIOLOGICAL

Live, infectious, aseptic, purified, vialed, cryopreserved, Plasmodium falciparum sporozoites, strain NF54

Group 1a (PfSPZ Vaccine); Group 1b (NS); Group 2a (PfSPZ Vaccine); Group 2b (NS); Group 3a (PfSPZ Vaccine); Group 3b (NS); Group 4a (PfSPZ Vaccine); Group 4b (NS)

Eligibility Criteria

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

You may qualify if:

• Healthy males and non-pregnant/non-lactating females, age 18 to 45 years at time of enrollment.
• Provision of signed and dated informed consent form.
• Demonstrate understanding of the study by responding correctly to 10 out of 10 true/false statements about the trial (a maximum of two additional attempts will be granted for those who fail to respond correctly to all true/false statements in their first attempt).
• Stated availability and willingness to comply with all study procedures and visits for the duration of the trial, including the required vaccination and post-CHMI ward observation period.
• Able to understand and communicate in Spanish, the national language of Equatorial Guinea
• Be in good general health as evidenced by medical history, screening physical examination and laboratory findings.
• Females of child bearing potential must agree to use injectable medroxyprogesterone for at least 4 weeks prior to enrollment and agree to continue to use medroxyprogesterone during the entire study period.
• Female subjects must not be pregnant (as demonstrated by a negative urine pregnancy test) at enrollment and prior to each immunization.
• Body Mass Index (BMI) of 18 to 30 kg/m2.
• At least one year of residence on Bioko Island, Equatorial Guinea, and living close enough to Baney Clinical Research Center and Sampaka Hospital to be able to attend the required appointments at the study center.
• Agree to release medical information and inform a study doctor about contraindications for participation in the study.
• Willingness to be attended to by a study doctor and take all medications prescribed during the study period.
• Agree to provide contact information of a third-party household member or close friend to the study team.
• Agree not to participate in another clinical trial during the study period.
• Agree not to donate blood during the study period.

You may not qualify if:

• Known allergic reactions to components of PfSPZ Vaccine, PfSPZ Challenge, or artemether-lumefantrine (AL).
• Having received an investigational malaria vaccine in the last 5 years.
• Having received any non-live vaccine in the 14 days prior to enrollment, any live vaccine in the 28 days prior to enrollment or three or more of any type of vaccine in the four months prior to enrollment.
• Participation in any other clinical study involving investigational medicinal products including malaria drugs within 30 days prior to enrollment.
• History of arrhythmias, prolonged QT-interval or other cardiac disease, or clinically significant abnormalities on electrocardiogram (ECG) at screening.
• History of non-febrile seizures or complex febrile seizures.
• History of cardiac disease in a 1st or 2nd degree relative when \<50 years of age.
• A chronic illness including diabetes mellitus, cancer, HIV/AIDS, tuberculosis.
• History of illicit drug or alcohol use that interferes with normal social function.
• The use of chronic immunosuppressive drugs or other immune modifying drugs within three months of study onset (inhaled and topical corticosteroids are allowed) and during the study period.
• Any clinically significant deviation from the normal range in biochemistry, hematology or urinalysis tests.
• Positive HIV, hepatitis B virus or hepatitis C virus serologic tests.
• Signs and symptoms of tuberculosis (e.g., chronic cough, night sweats, chronic fever, enlarged lymph nodes, unintended weight loss), or risk factors in an otherwise healthy person in combination with a positive tuberculin skin test (TST).
• Symptoms, physical signs and/or laboratory values suggestive of systemic disorders including renal, hepatic, blood, cardiovascular, pulmonary, skin, immunodeficiency, psychiatric, and other conditions which could interfere with the interpretation of the study results or compromise the health of the volunteer.
• Any medical, psychiatric, social or occupational condition or situation that, in the judgment of the PI, impairs the volunteer's ability to give informed consent, increases the risk to the volunteer of participation in the study, affects the ability of the volunteer to participate fully in the study, or might negatively impact the quality, consistency or interpretation of data derived from their participation in the study.

Sponsors & Collaborators

• Sanaria Inc.: lead
• Ifakara Health Institute: collaborator
• Swiss Tropical & Public Health Institute: collaborator
• Government of Equatorial Guinea: collaborator
• Noble Oil Services: collaborator
• Marathon Oil Corporation: collaborator
• Atlantic Methanol Production Company: collaborator
• Equatorial Guinea (EG) liquefied natural gas (LNG): collaborator

Study Sites (1)

Baney Clinical Research Center

Santiago de Baney, Bioko Island, Equatorial Guinea

Location

Related Publications (1)

• Mpina M, Stabler TC, Schindler T, Raso J, Deal A, Acuche Pupu L, Nyakarungu E, Del Carmen Ovono Davis M, Urbano V, Mtoro A, Hamad A, Lopez MSA, Pasialo B, Eyang MAO, Rivas MR, Falla CC, Garcia GA, Momo JC, Chuquiyauri R, Saverino E, Preston Church LW, Kim Lee Sim B, Manguire B, Tanner M, Maas C, Abdulla S, Billingsley PF, Hoffman SL, Jongo S, Richie TL, Daubenberger CA. Diagnostic performance and comparison of ultrasensitive and conventional rapid diagnostic test, thick blood smear and quantitative PCR for detection of low-density Plasmodium falciparum infections during a controlled human malaria infection study in Equatorial Guinea. Malar J. 2022 Mar 24;21(1):99. doi: 10.1186/s12936-022-04103-y.

  PMID: 35331251 DERIVED

MeSH Terms

Conditions

Malaria; Malaria, Falciparum

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Said Jongo, MD, MMed

  Ifakara Health Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 12, 2018
• First Posted: July 18, 2018
• Study Start: July 30, 2018
• Primary Completion: March 12, 2019
• Study Completion: March 12, 2019
• Last Updated: January 7, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

EQ (1)