Safety, Tolerability, Immunogenicity and Protective Efficacy of PfSPZ Vaccine and PfSPZ-CVac in Indonesian Adults Against Naturally-Transmitted Malaria

Tahapan Penelitian : Rekrut
Sponsor:
Mitra Pelaksana:
Divisi Penyakit Tropik dan Infeksi, Departemen Ilmu Penyakit Dalam FKUI-RSCM; Pusat Riset Eijkman EOCRU; Pusat Kesehatan TNI Angkatan Darat
No Registry
INA-ZN6M5MG
Tanggal Input Registry : 17-05-2022

07-06-2022
1. To assess the safety and tolerability of PfSPZ Vaccine and PfSPZ-CVac compared to placebo in Indonesian soldiers. 2. To assess the protective efficacy (vaccine efficacy = VE) of PfSPZ Vaccine and PfSPZ-CVac against first clinical malaria cases caused by P. falciparum (Pf) identified by thick blood smear (TBS) microscopy in naturally exposed Indonesian soldiers.
1. To assess the VE of PfSPZ Vaccine and PfSPZ-CVac against first infections caused by Pf identified by TBS microscopy in naturally exposed Indonesian soldiers. 2. To assess the VE of PfSPZ Vaccine and PfSPZ-CVac against first clinical malaria cases caused by P. vivax (Pv) identified by TBS microscopy in naturally exposed Indonesian soldiers. 3. To assess the VE of PfSPZ Vaccine and PfSPZ-CVac against first infections caused by Pv identified by TBS microscopy in naturally exposed Indonesian soldiers. 4. To assess the VE of PfSPZ Vaccine and PfSPZ-CVac against relapsing infection from latent liver stages of Pv identified post-exposure in a malaria-free area. 5. To identify humoral immune responses that predict VE of PfSPZ Vaccine and/or PfSPZ-CVac. Exploratory: 1. To assess the VE of PfSPZ Vaccine and PfSPZ-CVac against all cases of clinical malaria caused by Pf and Pv identified by TBS microscopy in naturally exposed Indonesian soldiers. 2. To identify cellular immune responses that predict VE of PfSPZ Vaccine and PfSPZ-CVac. 3. To identify transcriptome or biomarker (protein) signatures that predict VE. 4. To identify markers of latent infection with Pv.
 
Safety, Tolerability, Immunogenicity and Protective Efficacy of PfSPZ Vaccine and PfSPZ-CVac in Indonesian Adults Against Naturally-Transmitted Malaria
Safety, Tolerability, Immunogenicity and Protective Efficacy Against Naturally-Transmitted Malaria in Eastern Indonesia of Two Plasmodium falciparum Sporozoite Vaccines, Sanaria® PfSPZ Vaccine and Sanaria® PfSPZ-CVac: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial in Healthy Indonesian Adults
Eksperimental
Sanaria® PfSPZ Vaccine: Radiation attenuated, aseptic, purified, cryopreserved Plasmodium falciparum sporozoites (PfSPZ) administered by direct venous inoculation (DVI). Normal Saline (0.9% NaCl): The placebo control administered by DVI. Sanaria® PfSPZ-CVac: Infectious, aseptic, purified, cryopreserved PfSPZ (Sanaria® PfSPZ Challenge) administered by DVI to individuals taking chloroquine (CQ) chemoprophylaxis. Normal Saline (0.9% NaCl): The placebo control administered by DVI to individuals taking CQ chemoprophylaxis. Diluent. The diluent for PfSPZ Vaccine and PfSPZ Challenge will be phosphate buffered saline (PBS) with 1% human serum albumin.
372
 

Inclusion Criteria:

1. A male aged 18-55 years at the time of screening. 2. Assigned to the battalion of study and programmed to accompany it to eastern Indonesia for the duration of the deployment. 3. Freely provides written informed consent to participate in the study. 4. Agrees to adhere to Indonesian military medical guidance regarding screening and treatment of malaria. 5. Physical examination and laboratory results without clinically significant findings and a body mass index (BMI) ≤35 kg/m2.

Exclusion Criteria:

1.Previous vaccination with an investigational malaria vaccine. 2. Use of an investigational or non-registered drug or vaccine other than the study vaccine(s) within 30 days before the first study vaccination, or planned use up to 30 days after last vaccination. 3. Chronic administration (defined as more than 14 days) of immunosuppressant or other immune-modifying drugs within six months before the first vaccination. This includes any dose level of oral steroids, but not inhaled steroids or topical steroids. 4. Administration or planned administration of 1 live or 3 or more other type vaccines in the period beginning 28 days before the first study vaccination and ending 28 days after the last vaccination. 5. Confirmed or suspected immunosuppressive or immunodeficient condition. 6. Confirmed or suspected autoimmune disease. 7. History of allergic reactions or anaphylaxis to CQ or other 4-aminoquinolone derivatives. 8. History of serious allergic reactions to a drug (anaphylaxis, or requiring hospitalization). 9. History of allergy to phosphate buffered saline or human serum albumin. 10. Use or planned use of any drug with anti-malarial activity during the course of the study except for antimalarial medication administered by study clinicians. 11. History of splenectomy. 12. Laboratory evidence of liver disease (the final decision will be made by the PI and clinical officers, but in general a participant will be excluded if any of the screening liver function tests (ALT, bilirubin, gamma GTP) are > double the upper limit of normal measured twice without an explanation for the abnormal values). 13. Laboratory evidence of renal disease (serum creatinine > 1.5 mg/dL, measured twice) 14. Laboratory evidence of hematologic disease (platelet count or hemoglobin 450 msec) or any signs of arrythmia/ irregularity, ischemia, cardiac enlargement considered indicative of acute or chronic cardiovascular disease. 16. Acute or chronic pulmonary, cardiovascular, hepatic, renal or neurological condition, severe malnutrition, or any other clinical findings that may increase the risk of participating in the study as determined by the principal investigator or her designee. 17. Administration of immunoglobulin and/or any blood products within the three months preceding the first study vaccination or planned administration during the study period. 18. Simultaneous participation in any other interventional clinical trial. 19. Other conditions that in the opinion of the principal investigator or her designee would jeopardize the safety or rights of a participant in the trial or would render the participant unable to comply with the protocol or might compromise the integrity of the data. 20. Any evidence of active malaria, whether symptomatic or asymptomatic, confirmed by RDT, microscopy or PCR before first injection of PfSPZ Vaccine or PfSPZ-CVac, unless treated by the clinical team. 21. History of non-febrile seizures or atypical febrile seizures. 22. Under treatment for tuberculosis. 23. Laboratory evidence of active infection with hepatitis B, hepatitis C or HIV. 24. Participants with > 10% 5-year cardiovascular risk (fatal and non-fatal) based on the Gaziano scoring system (Appendix A); participants in the 18–34-year-old age group will be assessed as though they are in the 35-44 age group. 25. History of psychiatric disorders (such as personality disorders, anxiety disorders, or schizophrenia) or behavioral tendencies (including active alcohol or drug abuse) discovered during the screening process that in the opinion of the investigator would make compliance with the protocol difficult.
 
Ethical Approval from Ethics Committee Faculty of Medicine University of Indonesia, letter no. 0228/UN2.F1/ETIK/2018 dated 19 Mar 2018; Renewal EC FKUI No. KET-234/UN2.F1/ETIK/PPM.00.02/2022 dated 07 Mar 2022; Ethical Approval from Oxford Tropical Research Ethics Committee (OxTREC) dated 07 Sep 2018
Not Applicable
PPUK No. B-PN.01.06.3.321.05.19.1739 dated 10 May 2019 and Extension of PPUK No. RG.01.06 .32.323.04.22.124 dated 13 Apr 2022
NCT03503058
Ms. Fitria Wulandari