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

NCT02613520 | Completed Phase 1 DMC

• 1 other identifier: BSPZV2
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 1

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.

Conditions

Malaria

Keywords

PfSPZ Vaccine; Plasmodium falciparum

Outcome Measures

Primary Outcomes (1)

• 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. 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).

  Post first immunization uptil 56 days post-CHMI or 56 days post-3rd immunization

Secondary Outcomes (4)

• Level of Antibodies against Pf proteins in volunteer sera

  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

  Post first immunization uptil 56 days post-CHMI or 56 days post-3rd immunization

• Quantitation of cellular immune responses against Pf proteins in volunteers

  Post first immunization uptil 56 days post-CHMI or 56 days post-3rd immunization

• Whole genome expression profiles of volunteer

  Post first immunization uptil 56 days post-CHMI or 56 days post-3rd immunization

Other Outcomes (2)

• Number of adult volunteers protected against CHMI following immunization

  28 days post CHMI

• Genetic profiles of Pf parasites

  Screening uptil 56 days post-CHMI or 56 days post-3rd immunization

Study Arms (23)

Group 1a (PfSPZ Vaccine)

EXPERIMENTAL

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; Biological: PfSPZ Challenge (for CHMI)

Group 1a (normal saline)

PLACEBO COMPARATOR

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; Biological: PfSPZ Challenge (for CHMI)

Group 1a (CHMI controls)

OTHER

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)

Group 1b (PfSPZ Vaccine)

EXPERIMENTAL

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; Biological: PfSPZ Challenge (for CHMI)

Group 1b (normal saline)

PLACEBO COMPARATOR

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; Biological: PfSPZ Challenge (for CHMI)

Group 1b (CHMI controls)

OTHER

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)

Group 2a (PfSPZ Vaccine)

EXPERIMENTAL

11-17 years; n=6; 3 doses of 9.0 x 10\^5 PfSPZ Vaccine given 8 weeks apart.

Biological: PfSPZ Vaccine

Group 2a (normal saline)

PLACEBO COMPARATOR

11-17 years; n=3; 3 doses of normal saline given 8 weeks apart.

Other: Normal Saline

Group 2b (PfSPZ Vaccine)

EXPERIMENTAL

11-17 years; n=6; 3 doses of 1.8 x 10\^6 PfSPZ Vaccine given 8 weeks apart.

Biological: PfSPZ Vaccine

Group 2b (normal saline)

PLACEBO COMPARATOR

11-17 years; n=3; 3 doses of normal saline given 8 weeks apart.

Other: Normal Saline

Group 3a (PfSPZ Vaccine)

EXPERIMENTAL

6-10 years; n=6; 3 doses of 9.0 x 10\^5 PfSPZ Vaccine given 8 weeks apart.

Biological: PfSPZ Vaccine

Group 3a (normal saline)

PLACEBO COMPARATOR

6-10 years; n=3; 3 doses of normal saline given 8 weeks apart.

Other: Normal Saline

Group 3b (PfSPZ Vaccine)

EXPERIMENTAL

6-10 years; n=6; 3 doses of 1.8 x 10\^6 PfSPZ Vaccine given 8 weeks apart.

Biological: PfSPZ Vaccine

Group 3b (normal saline)

PLACEBO COMPARATOR

6-10 years; n=3; 3 doses of normal saline given 8 weeks apart.

Other: Normal Saline

Group 4a (PfSPZ Vaccine)

EXPERIMENTAL

1-5 years; n=6; 3 doses of 4.5 x 10\^5 PfSPZ Vaccine given 8 weeks apart.

Biological: PfSPZ Vaccine

Group 4a (normal saline)

PLACEBO COMPARATOR

1-5 years; n=3; 3 doses of normal saline given 8 weeks apart.

Other: Normal Saline

Group 4b (PfSPZ Vaccine)

EXPERIMENTAL

1-5 years; n=6; 3 doses of 9.0 x 10\^5 PfSPZ Vaccine given 8 weeks apart.

Biological: PfSPZ Vaccine

Group 4b (normal saline)

PLACEBO COMPARATOR

1-5 years; n=3; 3 doses of normal saline given 8 weeks apart.

Other: Normal Saline

Group 5a (PfSPZ Vaccine)

EXPERIMENTAL

6-11 months; n=3; 1 dose of 2.7 x 10\^5 PfSPZ Vaccine.

Biological: PfSPZ Vaccine

Group 5b (PfSPZ Vaccine)

EXPERIMENTAL

6-11 months; n=6; 3 doses of 4.5 x 10\^5 PfSPZ Vaccine given 8 weeks apart.

Biological: PfSPZ Vaccine

Group 5b (normal saline)

PLACEBO COMPARATOR

6-11 months; n=3; 3 doses of normal saline given 8 weeks apart.

Other: Normal Saline

Group 5c (PfSPZ Vaccine)

EXPERIMENTAL

6-11 months; n=6; 3 doses of 9.0 x 10\^5 PfSPZ Vaccine given 8 weeks apart.

Biological: PfSPZ Vaccine

Group 5c (normal saline)

PLACEBO COMPARATOR

6-11 months; n=3; 3 doses of normal saline given 8 weeks apart.

Other: Normal Saline

Interventions

PfSPZ Vaccine BIOLOGICAL

Metabolically active, non-replicating, radiation attenuated, aseptic, purified, cryopreserved NF54 P. falciparum (Pf) sporozoites (PfSPZ Vaccine)

Group 1a (PfSPZ Vaccine); Group 1b (PfSPZ Vaccine); Group 2a (PfSPZ Vaccine); Group 2b (PfSPZ Vaccine); Group 3a (PfSPZ Vaccine); Group 3b (PfSPZ Vaccine); Group 4a (PfSPZ Vaccine); Group 4b (PfSPZ Vaccine); Group 5a (PfSPZ Vaccine); Group 5b (PfSPZ Vaccine); Group 5c (PfSPZ Vaccine)

Normal Saline OTHER

0.9% Sodium chloride

Group 1a (normal saline); Group 1b (normal saline); Group 2a (normal saline); Group 2b (normal saline); Group 3a (normal saline); Group 3b (normal saline); Group 4a (normal saline); Group 4b (normal saline); Group 5b (normal saline); Group 5c (normal saline)

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

Group 1a (CHMI controls); Group 1a (PfSPZ Vaccine); Group 1a (normal saline); Group 1b (CHMI controls); Group 1b (PfSPZ Vaccine); Group 1b (normal saline)

Eligibility Criteria

• Age: 6 Months - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sanaria Inc.: lead
• Ifakara Health Institute: collaborator
• Swiss Tropical & Public Health Institute: collaborator
• Medical Care Development, Inc.: collaborator
• Tanzania Commission for Science and Technology: collaborator
• Government of Equatorial Guinea: collaborator
• Marathon Oil Corporation: collaborator
• Noble Oil Services: collaborator

Study Sites (1)

Bagamoyo Research and Training center of the Ifakara Health Institute

Bagamoyo, Tanzania

Location

Related Publications (2)

• Jongo SA, Church LWP, Mtoro AT, Schindler T, Chakravarty S, Ruben AJ, Swanson PA, Kassim KR, Mpina M, Tumbo AM, Milando FA, Qassim M, Juma OA, Bakari BM, Simon B, James ER, Abebe Y, Kc N, Saverino E, Fink M, Cosi G, Gondwe L, Studer F, Styers D, Seder RA, Schindler T, Billingsley PF, Daubenberger C, Sim BKL, Tanner M, Richie TL, Abdulla S, Hoffman SL. Increase of Dose Associated With Decrease in Protection Against Controlled Human Malaria Infection by PfSPZ Vaccine in Tanzanian Adults. Clin Infect Dis. 2020 Dec 31;71(11):2849-2857. doi: 10.1093/cid/ciz1152.

  PMID: 31782768 DERIVED

• Schindler T, Jongo S, Studer F, Mpina M, Mwangoka G, Mswata S, Ramadhani K, Sax J, Church LWP, Richie TL, Tanner M, Hoffman SL, Abdulla S, Daubenberger C. Two cases of long-lasting, sub-microscopic Plasmodium malariae infections in adults from coastal Tanzania. Malar J. 2019 Apr 29;18(1):149. doi: 10.1186/s12936-019-2787-x.

  PMID: 31036014 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

• Said Jongo, MD, MMED

  Ifakara Health Institute (IHI), Bagamoyo, Tanzania

  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: November 17, 2015
• First Posted: November 24, 2015
• Study Start: December 1, 2015
• Primary Completion: February 1, 2017
• Study Completion: March 1, 2017
• Last Updated: October 15, 2018

Record last verified: 2017-12

Locations

TA (1)