Safety, Tolerability and Immunogenicity of PfSPZ Vaccine in an Age De-escalation Trial in Equatorial Guinea.

NCT02859350 | Completed Phase 1 DMC

• 1 other identifier: EGSPZV2
• Study Type: interventional
• Target: 135
• Locations: 1 country
• Sites: 1

Brief 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) 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).

Conditions

Malaria

Keywords

Plasmodium falciparum; PfSPZ Vaccine; PfSPZ Challenge (NF54); CHMI; Chloroquine; Chemoprophylaxis; PfSPZ-CVac

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).

  Day of first immunization until one year

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 (4)

• Time to P. falciparum parasitemia by microscopy over a period of 28 days following CHMI using PfSPZ Challenge by DVI in young adults (aged 18 to 35 years).

  Day of CHMI to 28 days later

• Proportion of volunteers who develop P. falciparum parasitemia by microscopy over a period of 28 days following CHMI using PfSPZ Challenge by DVI in young adults (aged 18 to 35 years).

  Day of CHMI to 28 days later

• Time to P. falciparum parasitemia by qPCR over a period of 28 days following CHMI using PfSPZ Challenge by DVI in young adults (aged 18 to 35 years).

  Day of CHMI to 28 days later

Study Arms (15)

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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 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) 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 (PfSPZ Vaccine); Group 1a (normal saline); Group 1b (PfSPZ CVac); Group 1b (normal saline)

Normal Saline OTHER

0.9% Sodium chloride

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) BIOLOGICAL

live, infectious, aseptic, purified, cryopreserved NF54 P. falciparum (Pf) sporozoites (PfSPZ Challenge)

Group 1b (PfSPZ CVac)

Eligibility Criteria

• Age: 6 Months - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

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

Study Sites (1)

La Paz Medical Center

Malabo, Equatorial Guinea

Location

Related Publications (1)

• 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.

  PMID: 37160281 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 (IHI)

  STUDY DIRECTOR

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: July 27, 2016
• First Posted: August 9, 2016
• Study Start: November 1, 2016
• Primary Completion: December 1, 2017
• Study Completion: February 1, 2018
• Last Updated: October 15, 2018

Record last verified: 2018-10

Locations

EQ (1)