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Safety and Immunogenicity in Age De-Escalation of PfSPZ Vaccine in Tanzanian Adults, Children, and Infants

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02613520
Recruitment Status : Completed
First Posted : November 24, 2015
Last Update Posted : October 15, 2018
Sponsor:
Collaborators:
Ifakara Health Institute
Swiss Tropical & Public Health Institute
Medical Care Development, Inc.
Tanzania Commission for Science and Technology
Government of Equatorial Guinea
Marathon Oil Corporation
Noble Oil Services
Information provided by (Responsible Party):
Sanaria Inc.

Brief Summary:
The present trial will evaluate safety and tolerability as well as the vaccine-induced humoral and cellular immune responses in healthy Tanzanian adults, adolescents, children, and infants who receive doses of 1.8x10^6, 9.0x10^5, 4.5x10^5 or 2.7x10^5 PfSPZ of PfSPZ Vaccine by direct venous inoculation (DVI),compared with control groups receiving normal saline (NS) placebo by DVI. In addition, as an exploratory objective, controlled human malaria infection (CHMI) will be used to assess efficacy in adults three weeks following immunization.

Condition or disease Intervention/treatment Phase
Malaria Biological: PfSPZ Vaccine Other: Normal Saline Biological: PfSPZ Challenge (for CHMI) Phase 1

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 105 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Clinical Trial to Evaluate the Safety and Immunogenicity in Age De-Escalation of Direct Venous Inoculation of a Plasmodium Falciparum Sporozoite Vaccine in Tanzanian Adults, Children, and Infants
Actual Study Start Date : December 2015
Actual Primary Completion Date : February 2017
Actual Study Completion Date : March 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria

Arm Intervention/treatment
Experimental: Group 1a (PfSPZ Vaccine)
18- 45 years; n=6; 3 doses of 9 x 10^5 PfSPZ Vaccine given 8 weeks apart. Volunteers will undergo CHMI with PfSPZ Challenge 3 weeks after the last immunization.
Biological: PfSPZ Vaccine
Metabolically active, non-replicating, radiation attenuated, aseptic, purified, cryopreserved NF54 P. falciparum (Pf) sporozoites (PfSPZ Vaccine)

Biological: 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

Placebo Comparator: Group 1a (normal saline)
18- 45 years; n=3; 3 doses of normal saline given 8 weeks apart. Volunteers will undergo CHMI with PfSPZ Challenge 3 weeks after the last immunization.
Other: Normal Saline
0.9% Sodium chloride

Biological: 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

Group 1a (CHMI controls)
18- 45 years; n=6; volunteers will not receive any intervention, but will serve only as infectivity controls; 3 volunteers each, for CHMI 1 and for CHMI 2 in Group 1a. Volunteers will be injected with PfSPZ Challenge (for CHMI).
Biological: 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

Experimental: Group 1b (PfSPZ Vaccine)
18- 45 years; n=6; 3 doses of 1.8 x 10^6 PfSPZ Vaccine given 8 weeks apart. Volunteers will undergo CHMI with PfSPZ Challenge 3 weeks after the last immunization.
Biological: PfSPZ Vaccine
Metabolically active, non-replicating, radiation attenuated, aseptic, purified, cryopreserved NF54 P. falciparum (Pf) sporozoites (PfSPZ Vaccine)

Biological: 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

Placebo Comparator: Group 1b (normal saline)
18- 45 years; n=3; 3 doses of normal saline given 8 weeks apart. Volunteers will undergo CHMI with PfSPZ Challenge 3 weeks after the last immunization.
Other: Normal Saline
0.9% Sodium chloride

Biological: 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

Group 1b (CHMI controls)
18- 45 years; n=6; volunteers will not receive any intervention, but will serve only as infectivity controls; 3 volunteers each, for CHMI 1 and for CHMI 2 in Group 1b. Volunteers will be injected with PfSPZ Challenge (for CHMI).
Biological: 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

Experimental: Group 2a (PfSPZ Vaccine)
11-17 years; n=6; 3 doses of 9.0 x 10^5 PfSPZ Vaccine given 8 weeks apart.
Biological: PfSPZ Vaccine
Metabolically active, non-replicating, radiation attenuated, aseptic, purified, cryopreserved NF54 P. falciparum (Pf) sporozoites (PfSPZ Vaccine)

Placebo Comparator: Group 2a (normal saline)
11-17 years; n=3; 3 doses of normal saline given 8 weeks apart.
Other: Normal Saline
0.9% Sodium chloride

Experimental: Group 2b (PfSPZ Vaccine)
11-17 years; n=6; 3 doses of 1.8 x 10^6 PfSPZ Vaccine given 8 weeks apart.
Biological: PfSPZ Vaccine
Metabolically active, non-replicating, radiation attenuated, aseptic, purified, cryopreserved NF54 P. falciparum (Pf) sporozoites (PfSPZ Vaccine)

Placebo Comparator: Group 2b (normal saline)
11-17 years; n=3; 3 doses of normal saline given 8 weeks apart.
Other: Normal Saline
0.9% Sodium chloride

Experimental: Group 3a (PfSPZ Vaccine)
6-10 years; n=6; 3 doses of 9.0 x 10^5 PfSPZ Vaccine given 8 weeks apart.
Biological: PfSPZ Vaccine
Metabolically active, non-replicating, radiation attenuated, aseptic, purified, cryopreserved NF54 P. falciparum (Pf) sporozoites (PfSPZ Vaccine)

Placebo Comparator: Group 3a (normal saline)
6-10 years; n=3; 3 doses of normal saline given 8 weeks apart.
Other: Normal Saline
0.9% Sodium chloride

Experimental: Group 3b (PfSPZ Vaccine)
6-10 years; n=6; 3 doses of 1.8 x 10^6 PfSPZ Vaccine given 8 weeks apart.
Biological: PfSPZ Vaccine
Metabolically active, non-replicating, radiation attenuated, aseptic, purified, cryopreserved NF54 P. falciparum (Pf) sporozoites (PfSPZ Vaccine)

Placebo Comparator: Group 3b (normal saline)
6-10 years; n=3; 3 doses of normal saline given 8 weeks apart.
Other: Normal Saline
0.9% Sodium chloride

Experimental: Group 4a (PfSPZ Vaccine)
1-5 years; n=6; 3 doses of 4.5 x 10^5 PfSPZ Vaccine given 8 weeks apart.
Biological: PfSPZ Vaccine
Metabolically active, non-replicating, radiation attenuated, aseptic, purified, cryopreserved NF54 P. falciparum (Pf) sporozoites (PfSPZ Vaccine)

Placebo Comparator: Group 4a (normal saline)
1-5 years; n=3; 3 doses of normal saline given 8 weeks apart.
Other: Normal Saline
0.9% Sodium chloride

Experimental: Group 4b (PfSPZ Vaccine)
1-5 years; n=6; 3 doses of 9.0 x 10^5 PfSPZ Vaccine given 8 weeks apart.
Biological: PfSPZ Vaccine
Metabolically active, non-replicating, radiation attenuated, aseptic, purified, cryopreserved NF54 P. falciparum (Pf) sporozoites (PfSPZ Vaccine)

Placebo Comparator: Group 4b (normal saline)
1-5 years; n=3; 3 doses of normal saline given 8 weeks apart.
Other: Normal Saline
0.9% Sodium chloride

Experimental: Group 5a (PfSPZ Vaccine)
6-11 months; n=3; 1 dose of 2.7 x 10^5 PfSPZ Vaccine.
Biological: PfSPZ Vaccine
Metabolically active, non-replicating, radiation attenuated, aseptic, purified, cryopreserved NF54 P. falciparum (Pf) sporozoites (PfSPZ Vaccine)

Experimental: Group 5b (PfSPZ Vaccine)
6-11 months; n=6; 3 doses of 4.5 x 10^5 PfSPZ Vaccine given 8 weeks apart.
Biological: PfSPZ Vaccine
Metabolically active, non-replicating, radiation attenuated, aseptic, purified, cryopreserved NF54 P. falciparum (Pf) sporozoites (PfSPZ Vaccine)

Placebo Comparator: Group 5b (normal saline)
6-11 months; n=3; 3 doses of normal saline given 8 weeks apart.
Other: Normal Saline
0.9% Sodium chloride

Experimental: Group 5c (PfSPZ Vaccine)
6-11 months; n=6; 3 doses of 9.0 x 10^5 PfSPZ Vaccine given 8 weeks apart.
Biological: PfSPZ Vaccine
Metabolically active, non-replicating, radiation attenuated, aseptic, purified, cryopreserved NF54 P. falciparum (Pf) sporozoites (PfSPZ Vaccine)

Placebo Comparator: Group 5c (normal saline)
6-11 months; n=3; 3 doses of normal saline given 8 weeks apart.
Other: Normal Saline
0.9% Sodium chloride




Primary Outcome Measures :
  1. Incidence and type of Adverse Events [ Time Frame: Post first immunization uptil 56 days post-CHMI or 56 days post-3rd immunization ]

    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).


Secondary Outcome Measures :
  1. 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 ]
    1. Antibody titres to pre-erythrocytic stage and erythrocytic stage antigens[PfCSP, PfLSA-1, PfEBA-175 , PfMSP-1, PfMSP-5, EXP-1] by ELISA
    2. Antibody titres to Pf sporozoites, asexual and sexual erythrocytic stage parasites by IFA.
    3. Analysis of antibodies to proteins in the Pf proteome array chip.

  2. 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 ]
    Capacity of sera from immunized volunteers to inhibit sporozoite invasion (ISI) of hepatocytes in vitro by ISI assay

  3. 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 ]
    1. 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.
    2. Identification of numbers of vaccine induced CD4 and CD8 T cells following FluoroSpot assay after stimulation with PfSPZ or Pf-infected erythrocytes.

  4. Whole genome expression profiles of volunteer [ Time Frame: Post first immunization uptil 56 days post-CHMI or 56 days post-3rd immunization ]
    Human gene expression profiling focusing on immune response genes in volunteers


Other Outcome Measures:
  1. Number of adult volunteers protected against CHMI following immunization [ Time Frame: 28 days post CHMI ]
    Evidence of vaccine-mediated protection against CHMI 3 weeks after last immunization in Groups 1 (adults) by preventing blood stage infection for 28 days (as detected by blood smear analysis and qPCR) following CHMI.

  2. Genetic profiles of Pf parasites [ Time Frame: Screening uptil 56 days post-CHMI or 56 days post-3rd immunization ]
    Whole genome sequencing of Plasmodium falciparum following break through infections.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   6 Months to 45 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy males and females, based on clinical and laboratory findings
  • From the age 6 months to 45 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 Bagamoyo town or nearby villages
  • 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
  • Agreement to provide contact information of a third party household member or close friend to study team
  • Availability through mobile phone 24 hours during the entire study period
  • 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) and parent or guardian signing 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 parasitaemia by blood smear at enrolment
  • Free from helminth infections at enrolment, or diagnosed with helminthes and treated appropriately to eliminate infestation
  • Female volunteers aged 9 years and above must be non-pregnant (as demonstrated by a negative serum 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

Exclusion Criteria:

  • Previous receipt of an investigational malaria vaccine or drug in the last 5 years
  • Participation in any other clinical study involving investigational medicinal products 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
  • 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 suspected as having clinically active TB by history or physical examination with positive QuantiFERON-TB Gold Test In-Tube assay
  • 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, affect the ability of the volunteer to participate in the study or impair interpretation of the study data

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02613520


Locations
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Tanzania
Bagamoyo Research and Training center of the Ifakara Health Institute
Bagamoyo, Tanzania
Sponsors and Collaborators
Sanaria Inc.
Ifakara Health Institute
Swiss Tropical & Public Health Institute
Medical Care Development, Inc.
Tanzania Commission for Science and Technology
Government of Equatorial Guinea
Marathon Oil Corporation
Noble Oil Services
Investigators
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Principal Investigator: Said Jongo, MD, MMED Ifakara Health Institute (IHI), Bagamoyo, Tanzania

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Sanaria Inc.
ClinicalTrials.gov Identifier: NCT02613520     History of Changes
Other Study ID Numbers: BSPZV2
First Posted: November 24, 2015    Key Record Dates
Last Update Posted: October 15, 2018
Last Verified: December 2017
Keywords provided by Sanaria Inc.:
PfSPZ Vaccine
Plasmodium falciparum
Additional relevant MeSH terms:
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Malaria
Protozoan Infections
Parasitic Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs