MalariaPhase 1NCT02418962
Safety and Immunogenicity of Direct Venous Inoculation of a Radiation-attenuated PfSPZ Vaccine in Equatoguinean Adults
A Phase 1 study testing PfSPZ Vaccine and Normal Saline in people with Malaria and Plasmodium Falciparum, run by Sanaria Inc. at 1 site in Equatorial Guinea.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 35 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Malaria, Plasmodium Falciparum
- What is being tested?
- PfSPZ Vaccine and Normal Saline
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 33 participants
- Where
- 1 siteEquatorial Guinea
- Study dates
- Mar 2015to Feb 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Show all 16Show fewer
- 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.
Who cannot join
- 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.
Show all 18Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
Equatorial Guinea1 site
La Paz Medical Center
Malabo
About this study
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
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:
Read more
- 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.
Read the 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.
- Conditions
- Malaria, Plasmodium Falciparum
- Being tested
- PfSPZ Vaccine, Normal Saline
- Keywords
- PfSPZ Vaccine
- Medical subject headings
- Malaria, Malaria, Falciparum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PfSPZ VaccineBiological
Aseptic, purified, metabolically active, non-replicating (live, radiation attenuated) cryopreserved Plasmodium falciparum sporozoites vaccine
Normal SalineOther
0.9% Sodium chloride solution for injection
| Study group | Role | What they receive |
|---|---|---|
| Group 1 (pilot group) | Experimental | 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. Receives: Biological: PfSPZ Vaccine |
| Group 2 | Experimental | 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 Receives: Biological: PfSPZ Vaccine |
| Group 3 | Placebo comparator | 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. Receives: Other: Normal Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Until 28 days after each vaccination
Number of serious adverse events
Occurrence of serious adverse events during the study period.
Measured: From first vaccination upto 50 weeks
Number of Pf infections
Occurrence of Pf infection of vaccine type detected at any point after the first vaccination (retrospectively determined).
Measured: From first vaccination upto 50 weeks
Secondary outcomes (3)
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.
Measured: 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.
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.
Measured: 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
Measured: Screening and at 2 and 24 weeks after the last vaccination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2015 (estimated)
- Study startMar 2015
- Primary completionSep 2015
- Study completionFeb 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MalariaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanaria Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Ifakara Health Institute, Swiss Tropical & Public Health Institute, Government of Equatorial Guinea, Hospital Universitario La Paz, Marathon Oil Corporation, Noble Oil Services
- Responsible party
- Sponsor
- Investigators
- Salim Abdulla, MD, PhD, Principal investigator, Ifakara Health Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02418962
- Sponsor's protocol ID
- EGSPZV1
- Status last verified
- Mar 2016
- First submitted
- 9 Apr 2015
- Last updated
- 2 Mar 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 29141739
Study at a glance
From the registry record, last updated by the sponsor on 2 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02418962
- Acronym / sponsor ID
- EGSPZV1
- Conditions
- Malaria, Plasmodium Falciparum
- Keywords
- PfSPZ Vaccine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Sanaria Inc.Industry (pharma, biotech, devices)
- Collaborators
- Ifakara Health Institute, Swiss Tropical & Public Health Institute, Government of Equatorial Guinea, Hospital Universitario La Paz, Marathon Oil Corporation, Noble Oil Services
- Study start
- Mar 2015
- Primary completion
- Sep 2015 (actual)
- Study completion
- Feb 2016 (actual)
- First posted
- 17 Apr 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group 1 (pilot group) | Experimental | Biological: PfSPZ VaccineGroup 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. |
| Group 2 | Experimental | Biological: PfSPZ VaccineThe 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 |
| Group 3 | Placebo comparator | Other: Normal SalineThe 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. |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (16 listed)
- 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.
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PfSPZ VaccineAseptic, purified, metabolically active, non-replicating (live, radiation attenuated) cryopreserved Plasmodium falciparum sporozoites vaccine | Biological | Group 1 (pilot group), Group 2 |
| Normal Saline0.9% Sodium chloride solution for injection | Other | Group 3 |
Primary outcome
Number of adverse events as a measure of safety and tolerability
Time frame: Until 28 days after each vaccination
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
Time frame: From first vaccination upto 50 weeks
Occurrence of serious adverse events during the study period.
Number of Pf infections
Time frame: From first vaccination upto 50 weeks
Occurrence of Pf infection of vaccine type detected at any point after the first vaccination (retrospectively determined).
3 secondary outcomes
Antibody titers to PfCSP, PfLSA-1, PfEXP-1 and PfMSP-5 by ELISA
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.
Antibody titers to whole Pf sporozoite by Immunofluorescence (IFA)
Time frame: Before each vaccination, 2 and 4 weeks after each vaccination, and at 8, and 24 weeks after the last vaccination.
Cellular immune responses
Time frame: Screening and at 2 and 24 weeks after the last vaccination
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Mar 2016.
- Derived from this study: PubMed 29141739Olotu 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.
Related trials for Malaria
Active, not recruitingObservational study
Trajectories and Mechanisms of Recovery From Malaria: An Observational Study
Malaria
Not yet recruiting
Positron Emission Tomography and Organ-Specific Changes in Participants Co-Enrolled in NIH Studies of Plasmodium Vivax Controlled Human Malaria Infection
Healthy Volunteer, Malaria
Recruiting
The Effects of Iron Treatment on Vaccine Immunogenicity in Kenyan Infants With Iron Deficiency
Iron Deficiencies
RecruitingObservational study
Host and Parasite Factors That Influence Susceptibility to Malaria Infection and Disease During Pregnancy and Early Childhood in Ouelessebougou and Bamako, Mali
Malaria
RecruitingPhase 1
Safety, Tolerability and Efficacy of PfSPZ-LARC2 Vaccine Against CHMI in Malaria-Naïve Adults
Malaria Falciparum
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Salim Abdulla, MD, PhD principal investigator
Ifakara Health Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PfSPZ Vaccine and Normal Saline in people with Malaria and Plasmodium Falciparum, run by Sanaria Inc. at 1 site in Equatorial Guinea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Equatorial Guinea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of adverse events as a measure of safety and tolerability (time frame: Until 28 days after each vaccination). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02418962, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Mar 2016.