MalariaPhase 1NCT02859350
Safety, Tolerability and Immunogenicity of PfSPZ Vaccine in an Age De-escalation Trial in Equatorial Guinea.
A Phase 1 study testing PfSPZ Vaccine, PfSPZ Challenge (for CHMI) and Normal Saline in people with Malaria, run by Sanaria Inc. at 1 site in Equatorial Guinea.
Trial summary
This trial will evaluate the safety, tolerability, and immunogenicity of PfSPZ Vaccine in healthy Equatoguinean adults, adolescents, children and infants who receive doses of 0.9x10^6, 1.8x10^6 or 2.7x10^6 PfSPZ Vaccine via direct venous inoculation (DVI) compared with control groups receiving normal saline (NS)… Read more about this study
- Who is it for?
- Ages 6 months to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria
- What is being tested?
- PfSPZ Vaccine, PfSPZ Challenge (for CHMI) and Normal Saline
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 135 participants
- Where
- 1 siteEquatorial Guinea
- Study dates
- Nov 2016to Feb 2018
- 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 6 months to 65 years
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Healthy males and females, based on clinical and laboratory findings
- From the age 6 months to 65 years
- Adults with a Body Mass Index (BMI) 18 to 30 Kg/m2; or adolescents, children and infants with Z-score of the selected indicator ([weight-for-height], [(height and BMI) for age]) category within ±2SD as detailed in protocol
- Long-term (at least one year) or permanent residence in the Baney district or Malabo city
- Agreement to release medical information and to inform the study doctor concerning contraindications for participation in the study
- Willingness to be attended to by a study clinician and take all necessary medications prescribed during study period
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- Agreement to provide contact information of a third party household member or close friend to study team
- Agreement not to participate in another clinical trial during the study period
- Agreement not to donate blood during the study period
- Able and willing to complete the study visit schedule over the study follow up period, including the hospitalizations required for protocol compliance
- .Willingness to undergo HIV, hepatitis B (HBV) and hepatitis C (HCV) tests
- Volunteer (subjects 18 years of age and older) or the parent / guardian signing the informed consent (for subjects <18 years of age) is able to demonstrate their understanding of the study by responding correctly to 10 out of 10 true/false statements (in a maximum of two attempts for those who failed to respond correctly to all true/false statements in the first attempt).
- Signed written informed consent, in accordance with local practice, provided by adult volunteers, parents or legal representatives and relevant assent for children participants as applicable.
- Free from malaria parasitemia by blood smear at enrollment and by PCR for group 1
- Has not been treated with any antimalarial medication for at least two weeks prior to the first immunization.
- Free from helminth infections (detected by microscopy) at enrollment.
- Female volunteers aged 9 years and above must be non-pregnant (as demonstrated by a negative urine pregnancy test), and provide consent/assent of their willingness to take protocol-defined measures not to become pregnant during the study and safety follow-up period.
Who cannot join
- Previous receipt of an investigational malaria vaccine in the last 5 years
- Participation in any other clinical study involving investigational medicinal products including investigational malaria drugs within 30 days prior to the onset of the study or during the study period
- History of arrhythmias or prolonged QT-interval or other cardiac disease, or clinically significant abnormalities in electrocardiogram (ECG) at screening
- Positive family history in a 1st or 2nd degree relative for cardiac disease at age <50 years old
- A history of psychiatric disease
- Suffering from any chronic illness including; diabetes mellitus, cancer or HIV/AIDS
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- Any confirmed or suspected immunosuppressive or immune-deficient condition, including asplenia
- History of drug or alcohol abuse interfering 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 or hematology blood tests or in urine analysis
- Positive HIV, hepatitis B virus or hepatitis C virus tests
- Volunteers who are have risk factors for tuberculosis and/or signs and symptoms of tuberculosis (TB), plus a positive tuberculin skin test (TST).
- 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
- Any medical, social condition, or occupational reason that, in the judgment of the investigator, is a contraindication to protocol participation or impairs the volunteer's ability to give informed consent, increases the risk to the volunteer because of participation in the study, affects the ability of the volunteer to participate in the study or impairs the quality, consistency or interpretation of the study data
- History of non-febrile seizures or atypical febrile seizures
Trial locations and contacts
1 site in 1 country.
Equatorial Guinea1 site
La Paz Medical Center
Malabo
About this study
Official title: Age Escalation / De-escalation Study to Evaluate the Safety, Tolerability and Immunogenicity of a Radiation-attenuated Plasmodium Falciparum (Pf) Sporozoite Vaccine (PfSPZ Vaccine) in Equatoguinean Adults, Children and Infants, and Comparison With Non-attenuated Pf Sporozoites (PfSPZ Challenge) Administered Under Chloroquine Prophylaxis (PfSPZ-CVac Approach) for Efficacy Against Controlled Human Malaria Infection.
This trial will evaluate the safety, tolerability, and immunogenicity of PfSPZ Vaccine in healthy Equatoguinean adults, adolescents, children and infants who receive doses of 0.9x10^6, 1.8x10^6 or 2.7x10^6 PfSPZ Vaccine via direct venous inoculation (DVI) compared with control groups receiving normal saline (NS) placebo by DVI. In addition, the study will also assess a second PfSPZ-based vaccination approach known as PfSPZ-CVac- the administration of non-irradiated, infectious PfSPZ (PfSPZ Challenge) (1x10^5 PfSPZ) under anti-malarial chemoprophylaxis (chloroquine) in younger adults ages 18 to 35 years for safety, tolerability, immunogenicity and efficacy against controlled human malaria infection (CHMI).
Read the detailed description
EGSPZV2 is a single center, double-blind, placebo-controlled trial. The study is to take place at the Baney Temporary Research Facility (BTRF) located in Baney City. One hundred and thirty-five healthy male and female; adults, adolescents, children and infant volunteers, aged from 6 months to 65 years who live in the Baney district and Malabo city on Bioko Island will be enrolled based on pre-defined inclusion and exclusion criteria implemented according to international ethical standards.
The trial will consist of seven groups (Group 1a: younger adults, ages 18-35; Group 2: older adults, ages 36-65; Group 3: adolescents, ages 11-17; Group 4: older children, ages 6-10; Group 5: younger children, ages 1-5; Groups 6a/b: infants, ages 6 months - 11 months) of volunteers. Vaccination will begin in Group 1a (younger adults), with three doses of 2.7x10^6 PfSPZ Vaccine given eight weeks apart by DVI. An eighth group (Group 1b: younger adults, ages 18- 35), will be uniquely immunized with the comparator vaccine PfSPZ Challenge given under chloroquine prophylaxis (PfSPZ-CVac approach), rather than with PfSPZ Vaccine. A single PfSPZ-CVac younger adult group (group 1b) is included to provide a direct comparison with PfSPZ Vaccine (group 1a) for the ability to protect against CHMI. Each of the first two groups (1a and 1b) will have 20 participants receiving either PfSPZ Vaccine or PfSPZ Challenge and 6 participants receiving NS placebo by DVI, with treatment allocation randomized and double-blind. Volunteers in Group 1b will receive vaccinations 8 weeks after the initial vaccination of Group 1a. Volunteers in Group 1 (younger adults) will receive CHMI between 10 and 14 weeks post last vaccination (with a window of +/- 7 days on each side) and will be followed for 8 weeks following CHMI.
Group 2 (older adults) will receive three doses of 2.7x10^6 PfSPZ Vaccine. Group 2 will consist of 12 participants receiving PfSPZ Vaccine and 4 participants receiving NS placebo by DVI, given eight weeks apart. Group 3, 4, 5 and 6b will each have 12 participants receiving three doses of 1.8x10^6 PfSPZ Vaccine and 4 participants receiving NS, also given eight weeks apart. Group 6a will consist of 3 volunteers who will receive a single dose of 9.0 x10^5 PfSPZ Vaccine.
Sequential age groups will be staggered to allow assessment of safety and tolerability before further age de-escalation. To assure safety, vaccinations will start in younger adults and will progress to younger and older age groups using staggered start dates at approximately weekly intervals. Age escalation and initial age de-escalation will take place at the same time, hence Group 2 and 3 will be vaccinated at the same time. Progressively younger age groups will then be immunized. The decision to proceed with each of these steps will be made by the study team after a review of safety data from the previously vaccinated group(s). Three Safety Monitoring Committee (SMC) meetings are scheduled to review data prior to initiating the younger children and infant groups.
- Conditions
- Malaria
- Being tested
- PfSPZ Vaccine, PfSPZ Challenge (for CHMI), Normal Saline, PfSPZ Challenge (for PfSPZ-CVac)
- Keywords
- Plasmodium falciparum, PfSPZ Vaccine, PfSPZ Challenge (NF54), CHMI, Chloroquine, Chemoprophylaxis, PfSPZ-CVac
- 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
Metabolically active, non-replicating, radiation attenuated, aseptic, purified, cryopreserved NF54 P. falciparum (Pf) sporozoites (PfSPZ Vaccine)
PfSPZ Challenge (for CHMI)Biological
live, infectious, aseptic, purified, cryopreserved NF54 P. falciparum (Pf) sporozoites (PfSPZ Challenge) Controlled human malaria infection (CHMI) by direct venous inoculation of 3,200 PfSPZ Challenge
Normal SalineOther
0.9% Sodium chloride
PfSPZ Challenge (for PfSPZ-CVac)Biological
live, infectious, aseptic, purified, cryopreserved NF54 P. falciparum (Pf) sporozoites (PfSPZ Challenge)
| Study group | Role | What they receive |
|---|---|---|
| Group 1a (PfSPZ Vaccine) | Experimental | 18-35 years; n= 20; 3 doses of 2.7x10^6 PfSPZ Vaccine given eight weeks apart. Volunteers will receive CHMI between 10 and 14 weeks post last vaccination (with a window of +/-7 days on each side) and will be followed for 8 weeks following CHMI. Receives: Biological: PfSPZ Vaccine; Biological: PfSPZ Challenge (for CHMI) |
| Group 1a (normal saline) | Placebo comparator | 18-35 years; n=6; 3 doses of normal saline given 8 weeks apart. Volunteers will receive CHMI between 10 and 14 weeks post last dose of NS (with a window of +/-7 days on each side) and will be followed for 8 weeks following CHMI. Receives: Biological: PfSPZ Challenge (for CHMI); Other: Normal Saline |
| Group 1b (PfSPZ CVac) | Experimental | 18-35 years; n=20; 3 doses of 1.0x10^5 PfSPZ Challenge given every four weeks. Group 1b will start 8 weeks after Group 1a. Volunteers in Group 1b will receive their first immunization after the loading dose of chloroquine has been administered. Volunteers will receive CHMI between 10 and 14 weeks post last vaccination (with a window of +/-7 days on each side) and will be followed for 8 weeks following CHMI. Receives: Biological: PfSPZ Challenge (for CHMI); Biological: PfSPZ Challenge (for PfSPZ-CVac) |
| Group 1b (normal saline) | Placebo comparator | 18-35 years; n=6; 3 doses of normal saline given 4 weeks apart. Group 1b will start 8 weeks after Group 1a. Volunteers will receive CHMI between 10 and 14 weeks post last dose of NS (with a window of +/-7 days on each side) and will be followed for 8 weeks following CHMI. Receives: Biological: PfSPZ Challenge (for CHMI); Other: Normal Saline |
| Group 2 (PfSPZ Vaccine) | Experimental | 36-65 years; n=12; 3 doses of 2.7x10^6 PfSPZ Vaccine given 8 weeks apart. Group 2 will start 3 weeks after Group 1a. Receives: Biological: PfSPZ Vaccine |
| Group 2 (normal saline) | Placebo comparator | 36-65 years; n=4; 3 doses of normal saline given 8 weeks apart. Group 2 will start 3 weeks after Group 1a. Receives: Other: Normal Saline |
| Group 3 (PfSPZ Vaccine) | Experimental | 11-17 years; n=12; 3 doses of 1.8x10^6 PfSPZ Vaccine given 8 weeks apart. Group 3 will start 3 weeks after Group 1a. Receives: Biological: PfSPZ Vaccine |
| Group 3 (normal saline) | Placebo comparator | 11-17 years; n=4; 3 doses of normal saline given 8 weeks apart. Group 3 will start 3 weeks after Group 1a. Receives: Other: Normal Saline |
| Group 4 (PfSPZ Vaccine) | Experimental | 6-10 years; n=12; 3 doses of 1.8x10^6 PfSPZ Vaccine given 8 weeks apart. Group 4 will start 4 weeks after Group 1a. Receives: Biological: PfSPZ Vaccine |
| Group 4 (normal saline) | Placebo comparator | 6-10 years; n=4; 3 doses of normal saline given 8 weeks apart. Group 4 will start 4 weeks after Group 1a. Receives: Other: Normal Saline |
| Group 5 (PfSPZ Vaccine) | Experimental | 1-5 years; n=12; 3 doses of 1.8x10^6 PfSPZ Vaccine given 8 weeks apart. Group 5 will start 7 weeks after Group 1a. Receives: Biological: PfSPZ Vaccine |
| Group 5 (normal saline) | Placebo comparator | 1-5 years; n=4; 3 doses of normal saline given 8 weeks apart. Group 5 will start 7 weeks after Group 1a. Receives: Other: Normal Saline |
| Group 6a (PfSPZ Vaccine) | Experimental | 6-11 months; n=3; 1 dose of 9.0x10^5 PfSPZ Vaccine. Group 6a will start 7 weeks after Group 1a. Receives: Biological: PfSPZ Vaccine |
| Group 6b (PfSPZ Vaccine) | Experimental | 6-11 months; n=12; 3 doses of 1.8x10^6 PfSPZ Vaccine given 8 weeks apart. Group 6b will start 11 weeks after Group 1a. Receives: Biological: PfSPZ Vaccine |
| Group 6b (normal saline) | Placebo comparator | 6-11 months; n=4; 3 doses of normal saline given 8 weeks apart. Group 6b will start 11 weeks after Group 1a. Receives: Other: Normal Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and type of Adverse Events
Incidence and type of adverse events (including breakthrough infections), vital signs, clinical laboratory assessments, physical examination findings post first immunization onwards.
- Occurrence of solicited symptoms during a 7-day surveillance period after vaccination (day of vaccination (Vx) and +7 days post vaccination)
- Occurrence of unsolicited symptoms during a 28-day surveillance period after each vaccination.
- Occurrence of serious adverse events during the study period.
- Occurrence of Pf infection of vaccine type detected at any point after the first vaccination (retrospectively determined).
Measured: Day of first immunization until one year
Secondary outcomes (4)
Level of Antibodies against Pf proteins in volunteer sera
- Antibody titres to pre-erythrocytic stage and erythrocytic stage antigens[PfCSP, PfLSA-1, PfEBA-175 , PfMSP-1, PfMSP-5, EXP-1] by ELISA
- Antibody titres to Pf sporozoites, asexual and sexual erythrocytic stage parasites by IFA.
- Analysis of antibodies to proteins in the Pf proteome array chip.
Measured: Post first immunization uptil 56 days post-CHMI or 56 days post-3rd immunization
Inhibitory Capacity of Volunteer Sera against in vitro Sporozoite Invasion of Hepatocytes
Capacity of sera from immunized volunteers to inhibit sporozoite invasion (ISI) of hepatocytes in vitro by ISI assay
Measured: Post first immunization uptil 56 days post-CHMI or 56 days post-3rd immunization
Quantitation of cellular immune responses against Pf proteins in volunteers
- Identification of number of vaccine induced PBMCs following Intracellular cytokine staining by flow cytometry after stimulation with PfSPZ or Pf-infected erythrocytes, peptide pools and P. falciparum infected primary human hepatocyte cell lines.
- Identification of numbers of vaccine induced CD4 and CD8 T cells following FluoroSpot assay after stimulation with PfSPZ or Pf-infected erythrocytes.
Measured: Post first immunization uptil 56 days post-CHMI or 56 days post-3rd immunization
Whole genome expression profiles of volunteer
Human gene expression profiling focusing on immune response genes in volunteers
Measured: Post first immunization uptil 56 days post-CHMI or 56 days post-3rd immunization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2016 (estimated)
- Study startNov 2016
- Primary completionDec 2017
- Study completionFeb 2018
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
- 135 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, Marathon Oil Corporation, Noble Oil Services, La Paz Medical Center, Malabo, Equatorial Guinea
- Responsible party
- Sponsor
- Investigators
- Salim Abdulla, MD, PHD, Study director, Ifakara Health Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02859350
- Sponsor's protocol ID
- EGSPZV2
- Status last verified
- Oct 2018
- First submitted
- 27 Jul 2016
- Last updated
- 15 Oct 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Jongo SA, Urbano Nsue Ndong Nchama V, Church LWP, Olotu A, Manock SR, Schindler T, Mtoro A, Kc N, Devinsky O, Zan E, Hamad A, Nyakarungu E, Mpina M, Deal A, Bijeri JR, Ondo Mangue ME, Ntutumu Pasialo BE, Nguema GN, Rivas MR, Chemba M, Ramadhani KK, James ER, Stabler TC, Abebe Y, Riyahi P, Saverino ES, Sax J, Hosch S, Tumbo A, Gondwe L, Segura JL, Falla CC, Phiri WP, Hergott DEB, Garcia GA, Maas C, Murshedkar T, Billingsley PF, Tanner M, Ayekaba MO, Sim BKL, Daubenberger C, Richie TL, Abdulla S, Hoffman SL. Safety and Immunogenicity of Radiation-Attenuated PfSPZ Vaccine in Equatoguinean Infants, Children, and Adults. Am J Trop Med Hyg. 2023 May 9;109(1):138-146. doi: 10.4269/ajtmh.22-0773. Print 2023 Jul 5.
PubMed 37160281
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Age Escalation / De-escalation Study to Evaluate the Safety, Tolerability and Immunogenicity of a Radiation-attenuated Plasmodium Falciparum (Pf) Sporozoite Vaccine (PfSPZ Vaccine) in Equatoguinean Adults, Children and Infants, and Comparison With Non-attenuated Pf Sporozoites (PfSPZ Challenge) Administered Under Chloroquine Prophylaxis (PfSPZ-CVac Approach) for Efficacy Against Controlled Human Malaria Infection.
- ClinicalTrials.gov ID
- NCT02859350
- Acronym / sponsor ID
- EGSPZV2
- Conditions
- Malaria
- Keywords
- Plasmodium falciparum, PfSPZ Vaccine, PfSPZ Challenge (NF54), CHMI, Chloroquine, Chemoprophylaxis, PfSPZ-CVac
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 135 participants (actual)
- Lead sponsor
- Sanaria Inc.Industry (pharma, biotech, devices)
- Collaborators
- Ifakara Health Institute, Swiss Tropical & Public Health Institute, Government of Equatorial Guinea, Marathon Oil Corporation, Noble Oil Services, La Paz Medical Center, Malabo, Equatorial Guinea
- Study start
- Nov 2016 (actual)
- Primary completion
- Dec 2017 (actual)
- Study completion
- Feb 2018 (actual)
- First posted
- 9 Aug 2016 (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 trial will evaluate the safety, tolerability, and immunogenicity of PfSPZ Vaccine in healthy Equatoguinean adults, adolescents, children and infants who receive doses of 0.9x10^6, 1.8x10^6 or 2.7x10^6 PfSPZ Vaccine via direct venous inoculation (DVI) compared with control groups receiving normal saline (NS) placebo by DVI. In addition, the study will also assess a second PfSPZ-based vaccination approach known as PfSPZ-CVac- the administration of non-irradiated, infectious PfSPZ (PfSPZ Challenge) (1x10^5 PfSPZ) under anti-malarial chemoprophylaxis (chloroquine) in younger adults ages 18 to 35 years for safety, tolerability, immunogenicity and efficacy against controlled human malaria infection (CHMI).
Detailed description
EGSPZV2 is a single center, double-blind, placebo-controlled trial. The study is to take place at the Baney Temporary Research Facility (BTRF) located in Baney City. One hundred and thirty-five healthy male and female; adults, adolescents, children and infant volunteers, aged from 6 months to 65 years who live in the Baney district and Malabo city on Bioko Island will be enrolled based on pre-defined inclusion and exclusion criteria implemented according to international ethical standards.
The trial will consist of seven groups (Group 1a: younger adults, ages 18-35; Group 2: older adults, ages 36-65; Group 3: adolescents, ages 11-17; Group 4: older children, ages 6-10; Group 5: younger children, ages 1-5; Groups 6a/b: infants, ages 6 months - 11 months) of volunteers. Vaccination will begin in Group 1a (younger adults), with three doses of 2.7x10^6 PfSPZ Vaccine given eight weeks apart by DVI. An eighth group (Group 1b: younger adults, ages 18- 35), will be uniquely immunized with the comparator vaccine PfSPZ Challenge given under chloroquine prophylaxis (PfSPZ-CVac approach), rather than with PfSPZ Vaccine. A single PfSPZ-CVac younger adult group (group 1b) is included to provide a direct comparison with PfSPZ Vaccine (group 1a) for the ability to protect against CHMI. Each of the first two groups (1a and 1b) will have 20 participants receiving either PfSPZ Vaccine or PfSPZ Challenge and 6 participants receiving NS placebo by DVI, with treatment allocation randomized and double-blind. Volunteers in Group 1b will receive vaccinations 8 weeks after the initial vaccination of Group 1a. Volunteers in Group 1 (younger adults) will receive CHMI between 10 and 14 weeks post last vaccination (with a window of +/- 7 days on each side) and will be followed for 8 weeks following CHMI.
Group 2 (older adults) will receive three doses of 2.7x10^6 PfSPZ Vaccine. Group 2 will consist of 12 participants receiving PfSPZ Vaccine and 4 participants receiving NS placebo by DVI, given eight weeks apart. Group 3, 4, 5 and 6b will each have 12 participants receiving three doses of 1.8x10^6 PfSPZ Vaccine and 4 participants receiving NS, also given eight weeks apart. Group 6a will consist of 3 volunteers who will receive a single dose of 9.0 x10^5 PfSPZ Vaccine.
Sequential age groups will be staggered to allow assessment of safety and tolerability before further age de-escalation. To assure safety, vaccinations will start in younger adults and will progress to younger and older age groups using staggered start dates at approximately weekly intervals. Age escalation and initial age de-escalation will take place at the same time, hence Group 2 and 3 will be vaccinated at the same time. Progressively younger age groups will then be immunized. The decision to proceed with each of these steps will be made by the study team after a review of safety data from the previously vaccinated group(s). Three Safety Monitoring Committee (SMC) meetings are scheduled to review data prior to initiating the younger children and infant groups.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 15
| Arm | Type | Receives |
|---|---|---|
| Group 1a (PfSPZ Vaccine) | Experimental | Biological: PfSPZ Vaccine, Biological: PfSPZ Challenge (for CHMI)18-35 years; n= 20; 3 doses of 2.7x10^6 PfSPZ Vaccine given eight weeks apart. Volunteers will receive CHMI between 10 and 14 weeks post last vaccination (with a window of +/-7 days on each side) and will be followed for 8 weeks following CHMI. |
| Group 1a (normal saline) | Placebo comparator | Biological: PfSPZ Challenge (for CHMI), Other: Normal Saline18-35 years; n=6; 3 doses of normal saline given 8 weeks apart. Volunteers will receive CHMI between 10 and 14 weeks post last dose of NS (with a window of +/-7 days on each side) and will be followed for 8 weeks following CHMI. |
| Group 1b (PfSPZ CVac) | Experimental | Biological: PfSPZ Challenge (for CHMI), Biological: PfSPZ Challenge (for PfSPZ-CVac)18-35 years; n=20; 3 doses of 1.0x10^5 PfSPZ Challenge given every four weeks. Group 1b will start 8 weeks after Group 1a. Volunteers in Group 1b will receive their first immunization after the loading dose of chloroquine has been administered. Volunteers will receive CHMI between 10 and 14 weeks post last vaccination (with a window of +/-7 days on each side) and will be followed for 8 weeks following CHMI. |
| Group 1b (normal saline) | Placebo comparator | Biological: PfSPZ Challenge (for CHMI), Other: Normal Saline18-35 years; n=6; 3 doses of normal saline given 4 weeks apart. Group 1b will start 8 weeks after Group 1a. Volunteers will receive CHMI between 10 and 14 weeks post last dose of NS (with a window of +/-7 days on each side) and will be followed for 8 weeks following CHMI. |
| Group 2 (PfSPZ Vaccine) | Experimental | Biological: PfSPZ Vaccine36-65 years; n=12; 3 doses of 2.7x10^6 PfSPZ Vaccine given 8 weeks apart. Group 2 will start 3 weeks after Group 1a. |
| Group 2 (normal saline) | Placebo comparator | Other: Normal Saline36-65 years; n=4; 3 doses of normal saline given 8 weeks apart. Group 2 will start 3 weeks after Group 1a. |
| Group 3 (PfSPZ Vaccine) | Experimental | Biological: PfSPZ Vaccine11-17 years; n=12; 3 doses of 1.8x10^6 PfSPZ Vaccine given 8 weeks apart. Group 3 will start 3 weeks after Group 1a. |
| Group 3 (normal saline) | Placebo comparator | Other: Normal Saline11-17 years; n=4; 3 doses of normal saline given 8 weeks apart. Group 3 will start 3 weeks after Group 1a. |
| Group 4 (PfSPZ Vaccine) | Experimental | Biological: PfSPZ Vaccine6-10 years; n=12; 3 doses of 1.8x10^6 PfSPZ Vaccine given 8 weeks apart. Group 4 will start 4 weeks after Group 1a. |
| Group 4 (normal saline) | Placebo comparator | Other: Normal Saline6-10 years; n=4; 3 doses of normal saline given 8 weeks apart. Group 4 will start 4 weeks after Group 1a. |
| Group 5 (PfSPZ Vaccine) | Experimental | Biological: PfSPZ Vaccine1-5 years; n=12; 3 doses of 1.8x10^6 PfSPZ Vaccine given 8 weeks apart. Group 5 will start 7 weeks after Group 1a. |
| Group 5 (normal saline) | Placebo comparator | Other: Normal Saline1-5 years; n=4; 3 doses of normal saline given 8 weeks apart. Group 5 will start 7 weeks after Group 1a. |
| Group 6a (PfSPZ Vaccine) | Experimental | Biological: PfSPZ Vaccine6-11 months; n=3; 1 dose of 9.0x10^5 PfSPZ Vaccine. Group 6a will start 7 weeks after Group 1a. |
| Group 6b (PfSPZ Vaccine) | Experimental | Biological: PfSPZ Vaccine6-11 months; n=12; 3 doses of 1.8x10^6 PfSPZ Vaccine given 8 weeks apart. Group 6b will start 11 weeks after Group 1a. |
| Group 6b (normal saline) | Placebo comparator | Other: Normal Saline6-11 months; n=4; 3 doses of normal saline given 8 weeks apart. Group 6b will start 11 weeks after Group 1a. |
Who may qualify
- Ages
- 6 months to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (17 listed)
- Healthy males and females, based on clinical and laboratory findings
- From the age 6 months to 65 years
- Adults with a Body Mass Index (BMI) 18 to 30 Kg/m2; or adolescents, children and infants with Z-score of the selected indicator ([weight-for-height], [(height and BMI) for age]) category within ±2SD as detailed in protocol
- Long-term (at least one year) or permanent residence in the Baney district or Malabo city
- Agreement to release medical information and to inform the study doctor concerning contraindications for participation in the study
Key exclusion criteria (15 listed)
- Previous receipt of an investigational malaria vaccine in the last 5 years
- Participation in any other clinical study involving investigational medicinal products including investigational malaria drugs within 30 days prior to the onset of the study or during the study period
- History of arrhythmias or prolonged QT-interval or other cardiac disease, or clinically significant abnormalities in electrocardiogram (ECG) at screening
- Positive family history in a 1st or 2nd degree relative for cardiac disease at age <50 years old
- 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 VaccineMetabolically active, non-replicating, radiation attenuated, aseptic, purified, cryopreserved NF54 P. falciparum (Pf) sporozoites (PfSPZ Vaccine) | Biological | Group 1a (PfSPZ Vaccine), Group 2 (PfSPZ Vaccine), Group 3 (PfSPZ Vaccine), Group 4 (PfSPZ Vaccine), Group 5 (PfSPZ Vaccine), Group 6a (PfSPZ Vaccine), Group 6b (PfSPZ Vaccine) |
| PfSPZ Challenge (for CHMI)live, infectious, aseptic, purified, cryopreserved NF54 P. falciparum (Pf) sporozoites (PfSPZ Challenge) Controlled human malaria infection (CHMI) by direct venous inoculation of 3,200 PfSPZ Challenge | Biological | Group 1a (PfSPZ Vaccine), Group 1a (normal saline), Group 1b (PfSPZ CVac), Group 1b (normal saline) |
| Normal Saline0.9% Sodium chloride | Other | Group 1a (normal saline), Group 1b (normal saline), Group 2 (normal saline), Group 3 (normal saline), Group 4 (normal saline), Group 5 (normal saline), Group 6b (normal saline) |
| PfSPZ Challenge (for PfSPZ-CVac)live, infectious, aseptic, purified, cryopreserved NF54 P. falciparum (Pf) sporozoites (PfSPZ Challenge) | Biological | Group 1b (PfSPZ CVac) |
Primary outcome
Incidence and type of Adverse Events
Time frame: Day of first immunization until one year
Incidence and type of adverse events (including breakthrough infections), vital signs, clinical laboratory assessments, physical examination findings post first immunization onwards. 1. Occurrence of solicited symptoms during a 7-day surveillance period after vaccination (day of vaccination (Vx) and +7 days post vaccination) 2. Occurrence of unsolicited symptoms during a 28-day surveillance period after each vaccination. 3. Occurrence of serious adverse events during the study period. 4. Occurrence of Pf infection of vaccine type detected at any point after the first vaccination (retrospectively determined).
4 secondary outcomes
Level of Antibodies against Pf proteins in volunteer sera
Time frame: Post first immunization uptil 56 days post-CHMI or 56 days post-3rd immunization
Inhibitory Capacity of Volunteer Sera against in vitro Sporozoite Invasion of Hepatocytes
Time frame: Post first immunization uptil 56 days post-CHMI or 56 days post-3rd immunization
Quantitation of cellular immune responses against Pf proteins in volunteers
Time frame: Post first immunization uptil 56 days post-CHMI or 56 days post-3rd immunization
Whole genome expression profiles of volunteer
Time frame: Post first immunization uptil 56 days post-CHMI or 56 days post-3rd immunization
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 15 Oct 2018.
- Derived from this study: PubMed 37160281Jongo SA, Urbano Nsue Ndong Nchama V, Church LWP, Olotu A, Manock SR, Schindler T, Mtoro A, Kc N, Devinsky O, Zan E, Hamad A, Nyakarungu E, Mpina M, Deal A, Bijeri JR, Ondo Mangue ME, Ntutumu Pasialo BE, Nguema GN, Rivas MR, Chemba M, Ramadhani KK, James ER, Stabler TC, Abebe Y, Riyahi P, Saverino ES, Sax J, Hosch S, Tumbo A, Gondwe L, Segura JL, Falla CC, Phiri WP, Hergott DEB, Garcia GA, Maas C, Murshedkar T, Billingsley PF, Tanner M, Ayekaba MO, Sim BKL, Daubenberger C, Richie TL, Abdulla S, Hoffman SL. Safety and Immunogenicity of Radiation-Attenuated PfSPZ Vaccine in Equatoguinean Infants, Children, and Adults. Am J Trop Med Hyg. 2023 May 9;109(1):138-146. doi: 10.4269/ajtmh.22-0773. Print 2023 Jul 5.
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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 study director
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, PfSPZ Challenge (for CHMI) and Normal Saline in people with Malaria, 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 17 inclusion and 15 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 15 Oct 2018. 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?
Incidence and type of Adverse Events (time frame: Day of first immunization until one year). 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 NCT02859350, 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 15 Oct 2018.