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Safety and Immunogenicity of Direct Venous Inoculation of a Radiation-attenuated PfSPZ Vaccine in Equatoguinean Adults

Primary Purpose

Malaria, Plasmodium Falciparum

Status
Completed
Phase
Phase 1
Locations
Equatorial Guinea
Study Type
Interventional
Intervention
PfSPZ Vaccine
Normal Saline
Sponsored by
Sanaria Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Malaria focused on measuring PfSPZ Vaccine

Eligibility Criteria

18 Years - 35 Years (Adult)MaleAccepts Healthy Volunteers

Inclusion Criteria:

  • Healthy literate male aged between 18 - 35 years
  • Good health status based on history and clinical examination.
  • Long term (at least two year) or permanent residence in the city of Baney or community of Rebola, Bioko Island, Equatorial Guinea
  • Free from malaria parasitaemia by blood smear at screening
  • Not suffering from any chronic illness including HIV/AIDS.
  • Able and willing to come for complete one year follow up.
  • Answered correctly 10 out 10 questions demonstrating their understanding of study and study procedures.
  • Written informed consent.
  • Volunteer agrees to inform study doctor and agrees to release medical information concerning contra-indications for participation in the study.
  • Living with a third party who will contact the study team, if there is any alteration of consciousness during the first six months of the study.
  • Willingness to be attended by a study clinician and take all necessary medications prescribed during study period.
  • Availability through mobile phone 24 hours during the whole study period.
  • Agreement not to participate in another study during the study period.
  • Agreement not to donate blood during the study period.
  • Willingness to attend all study visits.
  • Willingness to undergo HIV, hepatitis B and hepatitis C tests.

Exclusion Criteria:

  • Plans to travel outside the Bioko, Equatorial Guinea in first nine months of the study.
  • Previous receipt of an investigational malaria vaccine or participation in a malaria drug study.
  • History of arrhythmias or prolonged QT-interval or other cardiac disease.
  • History of drug or alcohol abuse interfering with normal social function.
  • A history of psychiatric disease.
  • The use of chronic immunosuppressive drugs, antibiotics, or other immune modifying drugs within three months of study onset (inhaled and topical corticosteroids are allowed) and during the study period.
  • Symptoms, physical signs and 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 volunteers.
  • History of diabetes mellitus or cancer.
  • An estimated, ten year risk of fatal cardiovascular disease of ≥5%, as estimated by the Systematic Coronary Risk Evaluation (SCORE) system.
  • Clinically significant abnormalities in electrocardiogram (ECG) at screening.
  • Body Mass Index (BMI) below 18 or above 30 kg/m2.
  • Any clinically significant deviation from the normal range in biochemistry or hematology blood tests or in urine analysis or electrolytes.
  • Positive HIV, hepatitis B virus or hepatitis C virus tests.
  • Participation in any other clinical study within 30 days prior to the onset of the study or during the study period.
  • Volunteers unable to be closely followed for social, geographic or psychological reasons.
  • Study team employees and their immediate family relatives.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition, including asplenia.
  • Risk factor for clinically active tuberculosis + positive tuberculin skin test (TST)

Sites / Locations

  • La Paz Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

Group 1 (pilot group)

Group 2

Group 3

Arm Description

Group 1 will be comprised of 3 volunteers who will be vaccinated first before the rest for demonstration of safety. The safety volunteers will receive 2 escalating doses of PfSPZ vaccine at a two week interval, 1.35x10^5 and 2.7x10^5 PfSPZ.

The second group of 14 - 20 volunteers will receive three vaccinations of 2.7x10^5 PfSPZ Vaccine that will be given at 0, 8 and 16 weeks

The third group of 7 - 10 volunteers will act as control group for group 2 and will receive three injections of normal saline at 0, 8 and 16 weeks respectively.

Outcomes

Primary Outcome Measures

Number of adverse events as a measure of safety and tolerability
Occurrence of solicited adverse events during a 7-day surveillance period after vaccination (day of vaccination and study days 1, 2, 3, 4, 5 and 6). Occurrence of unsolicited adverse events during a 28-day surveillance period after each vaccination.
Number of serious adverse events
Occurrence of serious adverse events during the study period.
Number of Pf infections
Occurrence of Pf infection of vaccine type detected at any point after the first vaccination (retrospectively determined).

Secondary Outcome Measures

Antibody titers to PfCSP, PfLSA-1, PfEXP-1 and PfMSP-5 by ELISA
Antibody titers to PfCSP, PfLSA-1, PfEXP-1 and PfMSP-5 by ELISA, and their functional activity to block invasion of hepatocytes at screening, before each vaccination, at 2 and 4 weeks after the first and second vaccinations (groups 2 and 3) and at 2, 4, 8, and 24 weeks after the last vaccination.
Antibody titers to whole Pf sporozoite by Immunofluorescence (IFA)
Antibody titers to whole Pf sporozoite by Immunofluorescence (IFA) and their functional activity to block invasion of hepatocytes at screening, before each vaccination, 2 and 4 weeks after each vaccination, and at 8, and 24 weeks after the last vaccination.
Cellular immune responses
Cellular immune responses to the whole PfSPZ and synthetic peptides from selected Pf pre-erythrocytic antigens by ELISPOT and Intracellular Cytokine Staining (ICS) at screening and at 2 and 24 weeks after the last vaccination

Full Information

First Posted
April 9, 2015
Last Updated
March 1, 2016
Sponsor
Sanaria Inc.
Collaborators
Ifakara Health Institute, Swiss Tropical & Public Health Institute, Government of Equatorial Guinea, Hospital Universitario La Paz, Marathon Oil Corporation, Noble Oil Services
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1. Study Identification

Unique Protocol Identification Number
NCT02418962
Brief Title
Safety and Immunogenicity of Direct Venous Inoculation of a Radiation-attenuated PfSPZ Vaccine in Equatoguinean Adults
Official Title
Phase 1, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Safety and Immunogenicity of Direct Venous Inoculation of a Radiation-attenuated Plasmodium Falciparum Sporozoite Vaccine (PfSPZ Vaccine) in Equatoguinean Adults
Study Type
Interventional

2. Study Status

Record Verification Date
March 2016
Overall Recruitment Status
Completed
Study Start Date
March 2015 (undefined)
Primary Completion Date
September 2015 (Actual)
Study Completion Date
February 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanaria Inc.
Collaborators
Ifakara Health Institute, Swiss Tropical & Public Health Institute, Government of Equatorial Guinea, Hospital Universitario La Paz, Marathon Oil Corporation, Noble Oil Services

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a single center, randomized, placebo-controlled, double-blind trial to assess the safety and immunogenicity of PfSPZ Vaccine administered by direct venous inoculation (DVI). The study to be conducted in Baney District, Bioko Island, Equatorial Guinea (EG), will be to establish whether three doses of the higher regimen - three doses of 2.7x10^5 PfSPZ of the PfSPZ Vaccine administered at 8 week intervals - is as well-tolerated and efficacious in malaria exposed African adults as the five dose regimens. Specifically, the trial will address the following objectives: is the three dose regimen: Safe and well tolerated in Equatoguinean (EG) adults. As immunogenic in EG adults as is the five-dose regimen of 1.35x10^5 PfSPZ in Tanzanian and U.S. adults or as three-, four- and five-dose regimens of 2.7x10^5 PfSPZ being tested in Tanzanian, Malian and U.S. adults. In addition, as an exploratory objective, the volunteers in the EG trial will be followed longitudinally to measure the incidence of malaria during the initial six months following immunization, providing a preliminary assessment of efficacy.
Detailed Description
This is a single center, Phase 1, randomized, double-blind, placebo-controlled trial. Thirty-three healthy male volunteers, aged 18 to 35 years will be recruited into three groups. The first group will be comprised of 3 volunteers who will be vaccinated first before the rest for demonstration of safety. The safety volunteers will receive 2 escalating doses of PfSPZ vaccine at a two week interval, 1.35x10^5 and 2.7x10^5 PfSPZ. The second group of 14 - 20 volunteers will receive three vaccinations of 2.7x10^5 PfSPZ that will be given at 0, 8 and 16 weeks (in the Tanzania trial, volunteers will receive a five dose regimen at 0, 4, 8, 12 and 18 weeks). The third group of 7 - 10 volunteers will act as control group for group 2 and will receive three injections of normal saline at 0, 8 and 16 weeks respectively. Volunteers in groups 2 and 3 will only be injected when the Safety Monitoring Committee (SMC) provides clearance based on the results from the sentinel 3 volunteers (group 1). For groups 2 and 3, five volunteers will be vaccinated with the first dose before the remaining volunteers are vaccinated on a subsequent day. The control volunteers will help better assess the occurrence of adverse events compared to background disease patterns that occur in this tropical area. The decision to dose escalate in group 1 and to immunize a larger number of volunteers in group 2 in Bioko will be made with full knowledge of all safety data generated in other ongoing trials where the PfSPZ Vaccine is being tested.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malaria, Plasmodium Falciparum
Keywords
PfSPZ Vaccine

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
33 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group 1 (pilot group)
Arm Type
Experimental
Arm Description
Group 1 will be comprised of 3 volunteers who will be vaccinated first before the rest for demonstration of safety. The safety volunteers will receive 2 escalating doses of PfSPZ vaccine at a two week interval, 1.35x10^5 and 2.7x10^5 PfSPZ.
Arm Title
Group 2
Arm Type
Experimental
Arm Description
The second group of 14 - 20 volunteers will receive three vaccinations of 2.7x10^5 PfSPZ Vaccine that will be given at 0, 8 and 16 weeks
Arm Title
Group 3
Arm Type
Placebo Comparator
Arm Description
The third group of 7 - 10 volunteers will act as control group for group 2 and will receive three injections of normal saline at 0, 8 and 16 weeks respectively.
Intervention Type
Biological
Intervention Name(s)
PfSPZ Vaccine
Intervention Description
Aseptic, purified, metabolically active, non-replicating (live, radiation attenuated) cryopreserved Plasmodium falciparum sporozoites vaccine
Intervention Type
Other
Intervention Name(s)
Normal Saline
Intervention Description
0.9% Sodium chloride solution for injection
Primary Outcome Measure Information:
Title
Number of adverse events as a measure of safety and tolerability
Description
Occurrence of solicited adverse events during a 7-day surveillance period after vaccination (day of vaccination and study days 1, 2, 3, 4, 5 and 6). Occurrence of unsolicited adverse events during a 28-day surveillance period after each vaccination.
Time Frame
Until 28 days after each vaccination
Title
Number of serious adverse events
Description
Occurrence of serious adverse events during the study period.
Time Frame
From first vaccination upto 50 weeks
Title
Number of Pf infections
Description
Occurrence of Pf infection of vaccine type detected at any point after the first vaccination (retrospectively determined).
Time Frame
From first vaccination upto 50 weeks
Secondary Outcome Measure Information:
Title
Antibody titers to PfCSP, PfLSA-1, PfEXP-1 and PfMSP-5 by ELISA
Description
Antibody titers to PfCSP, PfLSA-1, PfEXP-1 and PfMSP-5 by ELISA, and their functional activity to block invasion of hepatocytes at screening, before each vaccination, at 2 and 4 weeks after the first and second vaccinations (groups 2 and 3) and at 2, 4, 8, and 24 weeks after the last vaccination.
Time Frame
Before each vaccination, at 2 and 4 weeks after 1st and 2nd vaccinations (groups 2 and 3) and at 2, 4, 8, and 24 weeks after the last vaccination.
Title
Antibody titers to whole Pf sporozoite by Immunofluorescence (IFA)
Description
Antibody titers to whole Pf sporozoite by Immunofluorescence (IFA) and their functional activity to block invasion of hepatocytes at screening, before each vaccination, 2 and 4 weeks after each vaccination, and at 8, and 24 weeks after the last vaccination.
Time Frame
Before each vaccination, 2 and 4 weeks after each vaccination, and at 8, and 24 weeks after the last vaccination.
Title
Cellular immune responses
Description
Cellular immune responses to the whole PfSPZ and synthetic peptides from selected Pf pre-erythrocytic antigens by ELISPOT and Intracellular Cytokine Staining (ICS) at screening and at 2 and 24 weeks after the last vaccination
Time Frame
Screening and at 2 and 24 weeks after the last vaccination

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Healthy literate male aged between 18 - 35 years Good health status based on history and clinical examination. Long term (at least two year) or permanent residence in the city of Baney or community of Rebola, Bioko Island, Equatorial Guinea Free from malaria parasitaemia by blood smear at screening Not suffering from any chronic illness including HIV/AIDS. Able and willing to come for complete one year follow up. Answered correctly 10 out 10 questions demonstrating their understanding of study and study procedures. Written informed consent. Volunteer agrees to inform study doctor and agrees to release medical information concerning contra-indications for participation in the study. Living with a third party who will contact the study team, if there is any alteration of consciousness during the first six months of the study. Willingness to be attended by a study clinician and take all necessary medications prescribed during study period. Availability through mobile phone 24 hours during the whole study period. Agreement not to participate in another study during the study period. Agreement not to donate blood during the study period. Willingness to attend all study visits. Willingness to undergo HIV, hepatitis B and hepatitis C tests. Exclusion Criteria: Plans to travel outside the Bioko, Equatorial Guinea in first nine months of the study. Previous receipt of an investigational malaria vaccine or participation in a malaria drug study. History of arrhythmias or prolonged QT-interval or other cardiac disease. History of drug or alcohol abuse interfering with normal social function. A history of psychiatric disease. The use of chronic immunosuppressive drugs, antibiotics, or other immune modifying drugs within three months of study onset (inhaled and topical corticosteroids are allowed) and during the study period. Symptoms, physical signs and 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 volunteers. History of diabetes mellitus or cancer. An estimated, ten year risk of fatal cardiovascular disease of ≥5%, as estimated by the Systematic Coronary Risk Evaluation (SCORE) system. Clinically significant abnormalities in electrocardiogram (ECG) at screening. Body Mass Index (BMI) below 18 or above 30 kg/m2. Any clinically significant deviation from the normal range in biochemistry or hematology blood tests or in urine analysis or electrolytes. Positive HIV, hepatitis B virus or hepatitis C virus tests. Participation in any other clinical study within 30 days prior to the onset of the study or during the study period. Volunteers unable to be closely followed for social, geographic or psychological reasons. Study team employees and their immediate family relatives. Any confirmed or suspected immunosuppressive or immunodeficient condition, including asplenia. Risk factor for clinically active tuberculosis + positive tuberculin skin test (TST)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Salim Abdulla, MD, PhD
Organizational Affiliation
Ifakara Health Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
La Paz Medical Center
City
Malabo
Country
Equatorial Guinea

12. IPD Sharing Statement

Citations:
PubMed Identifier
29141739
Citation
Olotu A, Urbano V, Hamad A, Eka M, Chemba M, Nyakarungu E, Raso J, Eburi E, Mandumbi DO, Hergott D, Maas CD, Ayekaba MO, Milang DN, Rivas MR, Schindler T, Embon OM, Ruben AJ, Saverino E, Abebe Y, Kc N, James ER, Murshedkar T, Manoj A, Chakravarty S, Li M, Adams M, Schwabe C, Segura JL, Daubenberger C, Tanner M, Richie TL, Billingsley PF, Lee Sim BK, Abdulla S, Hoffman SL. Advancing Global Health through Development and Clinical Trials Partnerships: A Randomized, Placebo-Controlled, Double-Blind Assessment of Safety, Tolerability, and Immunogenicity of PfSPZ Vaccine for Malaria in Healthy Equatoguinean Men. Am J Trop Med Hyg. 2018 Jan;98(1):308-318. doi: 10.4269/ajtmh.17-0449. Epub 2018 Jan 1.
Results Reference
derived

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Safety and Immunogenicity of Direct Venous Inoculation of a Radiation-attenuated PfSPZ Vaccine in Equatoguinean Adults

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