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

NCT02418962 | Completed Phase 1 DMC

• 1 other identifier: EGSPZV1
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

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:

1. 1.Safe and well tolerated in Equatoguinean (EG) adults.
2. 2.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.

Conditions

Malaria; Plasmodium Falciparum

Keywords

PfSPZ Vaccine

Outcome Measures

Primary Outcomes (3)

• 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.

  Until 28 days after each vaccination

• Number of serious adverse events

  Occurrence of serious adverse events during the study period.

  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).

  From first vaccination upto 50 weeks

Secondary Outcomes (3)

• Antibody titers to PfCSP, PfLSA-1, PfEXP-1 and PfMSP-5 by ELISA

  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)

  Before each vaccination, 2 and 4 weeks after each vaccination, and at 8, and 24 weeks after the last vaccination.

• Cellular immune responses

  Screening and at 2 and 24 weeks after the last vaccination

Study Arms (3)

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.

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

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.

Other: Normal Saline

Interventions

PfSPZ Vaccine BIOLOGICAL

Aseptic, purified, metabolically active, non-replicating (live, radiation attenuated) cryopreserved Plasmodium falciparum sporozoites vaccine

Group 1 (pilot group); Group 2

Normal Saline OTHER

0.9% Sodium chloride solution for injection

Group 3

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanaria Inc.: lead
• Ifakara Health Institute: collaborator
• Swiss Tropical & Public Health Institute: collaborator
• Government of Equatorial Guinea: collaborator
• Hospital Universitario La Paz: collaborator
• Marathon Oil Corporation: collaborator
• Noble Oil Services: collaborator

Study Sites (1)

La Paz Medical Center

Malabo, Equatorial Guinea

Location

Related Publications (1)

• 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.

  PMID: 29141739 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

• Salim Abdulla, MD, PhD

  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: April 9, 2015
• First Posted: April 17, 2015
• Study Start: March 1, 2015
• Primary Completion: September 1, 2015
• Study Completion: February 1, 2016
• Last Updated: March 2, 2016

Record last verified: 2016-03

Locations

EQ (1)