Study to Evaluate Safety, Immunogenicity and Efficacy of PfSPZ Vaccine in HIV Negative and HIV Positive Tanzanian Adults

NCT03420053 | Completed Phase 1 FDA Drug

• 1 other identifier: BSPZV3a
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, double-blind, placebo-controlled trial to evaluate safety and tolerability of PfSPZ Vaccine administered as five doses of 9.0x10\^5 PfSPZ or normal saline at 0, +2, +4, +6 and +28 days to healthy HIV negative adult volunteers and healthy HIV positive volunteers in Tanzania.

Conditions

Malaria; Malaria,Falciparum

Keywords

PfSPZ Vaccine; HIV+; Plasmodium falciparum; Sporozoites

Outcome Measures

Primary Outcomes (5)

• Safety of PfSPZ Vaccine - solicited symptoms

  Occurrence of solicited symptoms during a 7-day surveillance period after vaccination (day of vaccination (Vx) and +7 days post vaccination).

  From day of vaccination to 7-days post vaccination.

• Safety of PfSPZ Vaccine - unsolicited symptoms

  Occurrence of unsolicited symptoms during a 28-day surveillance period after each vaccination.

  From day of vaccination to 28-days post vaccination.

• Safety of PfSPZ Vaccine - laboratory abnormalities

  Occurrence of laboratory abnormalities including significant drops in CD4 T cell counts or increases in viral load.

  Day of immunization to approximately 11 weeks after the last vaccination (approximately 36 weeks).

• Safety of PfSPZ Vaccine - serious adverse events

  Occurrence of serious adverse events during the study period.

  Day of immunization to approximately 11 weeks after the last vaccination (approximately 36 weeks).

• Safety of PfSPZ Vaccine - breakthrough infection

  \- Occurrence of Pf infection of vaccine type detected at any point after the first vaccination (retrospectively determined).

  Day of immunization to approximately 11 weeks after the last vaccination (approximately 36 weeks).

Study Arms (5)

Group 1 HIV- vaccine recipients

EXPERIMENTAL

Group 1: n=6, HIV negative vaccine recipients will receive 9.0x10\^5 PfSPZ Vaccine at 0, +2, +4, +6 and +28 days. Total no. of volunteers in Group 1, n=9, where volunteers will be randomized in a 1:2 ratio to receive either normal saline placebo (NS) or PfSPZ Vaccine. Efficacy will be assessed by controlled human malaria infection (CHMI) at +3 weeks (+2 to +10 weeks) after the last dose of PfSPZ Vaccine. CHMI will be by DVI of 3,200 PfSPZ Challenge.

Biological: PfSPZ Vaccine; Biological: PfSPZ Challenge

Group 1 HIV- NS controls

PLACEBO COMPARATOR

Group 1: n=3, HIV negative NS placebo recipients will receive NS at 0, +2, +4, +6 and +28 days. Total no. of volunteers in Group 1, n=9, where volunteers will be randomized in a 1:2 ratio to receive either NS placebo or PfSPZ Vaccine. Efficacy will be assessed by CHMI at +3 weeks (+2 to +10 weeks) after the last dose of NS. CHMI will be by DVI of 3,200 PfSPZ Challenge.

Other: Normal Saline Placebo; Biological: PfSPZ Challenge

Group 2a HIV+ vaccine sentinels

EXPERIMENTAL

Group 2a: n=3, HIV positive vaccine recipients will receive 4.5x10\^5 PfSPZ Vaccine at 0, +2, +4, +6 and +28 days.

Biological: PfSPZ Vaccine

Group 2b HIV+ vaccine recipients

EXPERIMENTAL

Group 2b: n=6, HIV positive vaccine recipients will receive 9.0x10\^5 PfSPZ Vaccine at 0, +2, +4, +6 and +28 days. Total no. of volunteers in Group 2b, n=9, where volunteers will be randomized in a 1:2 ratio to receive either NS placebo or PfSPZ Vaccine. Efficacy will be assessed by CHMI at +3 weeks (+2 to +10 weeks) after the last dose of PfSPZ Vaccine. CHMI will be by DVI of 3,200 PfSPZ Challenge.

Biological: PfSPZ Vaccine; Biological: PfSPZ Challenge

Group 2b HIV+ placebo controls

PLACEBO COMPARATOR

Group 2b: n=3, HIV positive NS placebo recipients will receive NS at 0, +2, +4, +6 and +28 days. Total no. of volunteers in Group 2b, n=9, where volunteers will be randomized in a 1:2 ratio to receive either NS placebo or PfSPZ Vaccine. Efficacy will be assessed by CHMI at +3 weeks (+2 to +10 weeks) after the last dose of NS. CHMI will be by DVI of 3,200 PfSPZ Challenge.

Other: Normal Saline Placebo; Biological: PfSPZ Challenge

Interventions

PfSPZ Vaccine BIOLOGICAL

Aseptic, purified, metabolically active, non-replicating, radiation-attenuated, cryopreserved Pf sporozoites.

Group 1 HIV- vaccine recipients; Group 2a HIV+ vaccine sentinels; Group 2b HIV+ vaccine recipients

Normal Saline Placebo OTHER

0.9% sodium chloride solution

Group 1 HIV- NS controls; Group 2b HIV+ placebo controls

PfSPZ Challenge BIOLOGICAL

Aseptic, purified, live, infectious, cryopreserved Pf sporozoites.

Group 1 HIV- NS controls; Group 1 HIV- vaccine recipients; Group 2b HIV+ placebo controls; Group 2b HIV+ vaccine recipients

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male and female adults, from 18 to 45 years of age
• Long term (at least two years) or permanent residence in the Bagamoyo district or nearby districts in Coastal and Dar-es-Salaam regions
• Availability through mobile phone 24 hours a day during the whole study period
• Ability and willingness to complete the study visit schedule for safety follow-up and protocol compliance
• Agreement to provide personal contact information and contact information of a third party household member or close friend to study team
• Agreement not to participate in any other clinical study involving investigational medicinal products during the study period, except enrollment in observational studies (such a co-enrollment must be approved by the PI)
• Agreement to release medical and other information concerning contra-indications for participation in the study, and to be attended by a study clinician for physical examination and clinical investigations including electrocardiogram (ECG)
• Willingness to undergo all blood, urine and stool tests (as specified in the protocol) and additional tests that may be ordered by the study clinician to rule-out significant abnormality(ies)
• Female volunteers must be willing to take measures not to become pregnant if selected for participation in the trial and to undergo serum pregnancy test at screening and at defined time-points during the trial
• Volunteers for enrollment into HIV positive sub-groups must have:
• Documented HIV infection, be in general good health and on stable ART use for at least three (3) months, preferably six (6), prior to screening
• WHO clinical stage 1 of HIV disease
• CD4+ T-cell count \>500 cells/μL at screening
• Attending a care and treatment centre (CTC) within the study area for medical management of HIV infection, and agreeing to maintain regular attendance to such care and treatment centre while participating in the study
• Agreement to allow the clinical team to contact and coordinate care with the volunteer's HIV CTC.

You may not qualify if:

• Previous receipt of an investigational malaria vaccine or drug in the last 5 years
• Receipt of standard vaccinations within 4 weeks prior to the first immunization with a PfSPZ product or are planning to take standard vaccinations during the trial through 4 weeks following the last injection with a PfSPZ product
• Participation in any other clinical trial involving investigational medicinal products within 30 days prior to the onset of the study
• Clinically significant cardiac abnormalities as indicated by history, physical examination or clinically significant abnormalities in electrocardiogram (ECG)
• Positive family history in a 1st or 2nd degree relative for cardiac disease at age\< 50 years old
• A history of psychiatric disease
• History of afebrile seizures, atypical febrile seizures or epilepsy
• History of drug or alcohol abuse interfering with normal social function
• History of chronic immunodeficiency condition (other than HIV) or autoimmune disease
• The use of chronic immunosuppressive drugs, antibiotics, or other immune modifying drugs within three months prior to study onset (ART and inhaled and topical corticosteroids are allowed)
• Currently on Co-Trimoxazole (trimethoprim/sulfamethoxazole) prophylactic treatment (CPT)
• Body mass index (BMI) of \<18 or \>30 Kg/m2
• Females who are pregnant (as indicated by positive serum pregnancy test), nursing, or plan on becoming pregnant or nurse within the duration of trial
• Newly diagnosed with positive HIV infection at screening
• Positive hepatitis (B or C virus) tests

Sponsors & Collaborators

• Sanaria Inc.: lead
• Ifakara Health Institute: collaborator
• Swiss Tropical & Public Health Institute: collaborator
• Medical Care Development, Inc.: collaborator

Study Sites (1)

Bagamoyo Research and Training Center of the Ifakara Health Institute

Bagamoyo, Tanzania

Location

Related Publications (1)

• Jongo S, Church LWP, Milando F, Qassim M, Schindler T, Rashid M, Tumbo A, Nyaulingo G, Bakari BM, Athuman Mbaga T, Mohamed L, Kassimu K, Simon BS, Mpina M, Zaidi I, Duffy PE, Swanson PA 2nd, Seder R, Herman JD, Mendu M, Zur Y, Alter G, Kc N, Riyahi P, Abebe Y, Murshedkar T, James ER, Billingsley PF, Sim BKL, Richie TL, Daubenberger C, Abdulla S, Hoffman SL. Safety and protective efficacy of PfSPZ Vaccine administered to HIV-negative and -positive Tanzanian adults. J Clin Invest. 2024 Jan 9;134(6):e169060. doi: 10.1172/JCI169060.

  PMID: 38194272 DERIVED

MeSH Terms

Conditions

Malaria; Malaria, Falciparum

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• Said Jongo, MD, MMED

  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: December 13, 2017
• First Posted: February 5, 2018
• Study Start: February 7, 2018
• Primary Completion: August 25, 2018
• Study Completion: August 25, 2018
• Last Updated: April 5, 2019

Record last verified: 2019-04

Locations

TA (1)