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

NCT03503058 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: IDSPZV1
• Study Type: interventional
• Target: 345
• Locations: 1 country
• Sites: 2

Brief Summary

The study is a double-blind, randomized, placebo-controlled, Phase 2 clinical trial that will assess the safety, tolerability, immunogenicity and protective efficacy of PfSPZ Vaccine and PfSPZ-CVac against naturally occurring malaria in healthy Indonesian soldiers deployed to eastern Indonesia.

Conditions

Malaria

Keywords

Plasmodium falciparum; Sporozoites; PfSPZ

Outcome Measures

Primary Outcomes (2)

• Primary Safety Endpoint - The Number of Adverse Events Occurring After Investigational Product (IP) Administration

  1. The proportion of participants experiencing solicited AEs occurring within 7 days (PfSPZ Vaccine) or 14 days (PfSPZ-CVac) of each administration of investigational product (IP). 2. The proportion of participants experiencing serious adverse events (SAEs) deemed related to IP during active participation in the trial. 3. The proportion of participants experiencing unsolicited AEs occurring within 14 days of each administration of IP deemed related to vaccination or placebo administration.

  PfSPZ Vaccine: 7 days after each vaccination (2 days for local solicited AEs); PfSPZ-CVac: 14 days after each administration; SAEs for both products: from day of immunization until end of study (20 months-immunizations started ~2 months after FSFV).

• Primary Efficacy Endpoint - Number of Participants With First Clinical Pf Malaria Cases

  The deployment surveillance period was from 10 days after arriving in Papua to 2 days before departure (which was the last day that the clinical team had access to the study population). Primary endpoint: number of first clinical malaria cases caused by Pf among participants receiving vaccine (either vaccine group) vs. placebo (both placebo groups combined) during: * the first 24 weeks of deployment * the entire period of deployment (293 days, or approximately 42 weeks). Clinical malaria caused by Pf was defined as a positive thick blood smear (TBS) at any density (or PCR confirmed rapid diagnostic test) plus * measured axillary temperature ≥ 37.5 degrees Celsius or history of fever in the last 24 hours; or * at least two of the following symptoms/symptom groups: headache; chills and/or rigors; malaise and/or fatigue; dizziness and/or light-headedness; myalgias and/or arthralgias; or * meeting criteria for severe malaria (this third option was not used).

  First 24 weeks of deployment; the entire period of deployment (293 days, or approximately 42 weeks).

Secondary Outcomes (1)

• Secondary Efficacy Endpoint - Number of Confirmed First Infections Caused by Pf

  First 24 weeks of deployment; the entire period of deployment (293 days, or approximately 42 weeks).

Study Arms (4)

Group 1

EXPERIMENTAL

N=124 will receive PfSPZ Vaccine; three doses of 9x10\^5 PfSPZ of PfSPZ Vaccine administered by direct venous inoculation (DVI) given on day 1, 8 and 29.

Biological: PfSPZ Vaccine

Group 2

PLACEBO COMPARATOR

N=62 will receive normal saline; three doses of NS administered by DVI given on day 1, 8 and 29.

Other: Normal Saline

Group 3

EXPERIMENTAL

N=124 will receive PfSPZ Challenge under chloroquine (CQ) chemoprophylaxis; three doses of 2x10\^5 PfSPZ of PfSPZ Challenge administered by DVI on day 1, 29 and 57, with weekly CQ. Loading Dose: 10 mg/kg of CQ base (will be orally administered as a single loading dose to the participant by the study staff via directly observed therapy on PfSPZ-CVac Day -2. Weekly Dose: Subsequent doses of maintenance dose CQ (5 mg/kg CQ base) will be given weekly as a single dose, with the last dose 5 days after the last dose of PfSPZ Challenge.

Biological: PfSPZ Challenge under chloroquine (CQ) chemoprophylaxis

Group 4

PLACEBO COMPARATOR

N=62 will receive normal; three doses of NS administered by DVI given on day 1, 29 and 57, with weekly CQ. Loading Dose: 10 mg/kg of CQ base (will be orally administered as a single loading dose to the participant by the study staff via directly observed therapy on PfSPZ-CVac Day -2. Weekly Dose: Subsequent doses of maintenance dose CQ (5 mg/kg CQ base) will be given weekly as a single dose, with the last dose 5 days after the last dose of PfSPZ Challenge.

Other: Normal Saline; Drug: Chloroquine chemoprophylaxis alone

Interventions

PfSPZ Vaccine BIOLOGICAL

Radiation-attenuated, aseptic, purified, cryopreserved Plasmodium falciparum sporozoites (PfSPZ Vaccine)

Group 1

PfSPZ Challenge under chloroquine (CQ) chemoprophylaxis BIOLOGICAL

Infectious, aseptic, purified, cryopreserved Plasmodium falciparum sporozoites (PfSPZ Challenge) administered under CQ chemoprophylaxis Loading Dose: 10 mg/kg of CQ base (will be orally administered as a single loading dose to the participant by the study staff via directly observed therapy on PfSPZ-CVac Day -2. Weekly Dose: Subsequent doses of maintenance dose CQ (5 mg/kg CQ base) will be given weekly as a single dose, with the last dose 5 days after the last dose of PfSPZ Challenge.

Also known as: PfSPZ-CVac

Group 3

Normal Saline OTHER

0.9% Sodium chloride

Also known as: NS

Group 2; Group 4

Chloroquine chemoprophylaxis alone DRUG

Loading Dose: 10 mg/kg of CQ base (will be orally administered as a single loading dose to the participant by the study staff via directly observed therapy on NS Day -2. Weekly Dose: Subsequent doses of maintenance dose CQ (5 mg/kg CQ base) will be given weekly as a single dose, with the last dose 5 days after the last dose of NS.

Also known as: CQ

Group 4

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• A male aged 18-55 years at the time of screening.
• Assigned to the battalion of study and programmed to accompany it to eastern Indonesia for the duration of the deployment.
• Freely provides written informed consent to participate in the study.
• Agrees to adhere to Indonesian military medical guidance regarding screening and treatment of malaria.
• Physical examination and laboratory results without clinically significant findings that would jeopardize the safety of the participant or the integrity of the study, and a body mass index (BMI) ≤35 kg/m\^2.

You may not qualify if:

• Previous vaccination with an investigational malaria vaccine.
• 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.
• 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.
• 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.
• Confirmed or suspected immunosuppressive or immunodeficient condition.
• Confirmed or suspected autoimmune disease.
• History of allergic reactions or anaphylaxis to CQ or other 4-aminoquinolone derivatives.
• History of serious allergic reactions to a drug (anaphylaxis, or requiring hospitalization).
• History of allergy to phosphate buffered saline or human serum albumin.
• 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.
• History of splenectomy.
• Laboratory evidence of liver disease (the final decision will be made by the PI and clinical officers, but in general a volunteer 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).
• Laboratory evidence of renal disease (serum creatinine \> 1.5 mg/dL. measured twice).
• Laboratory evidence of hematologic disease (platelet count or hemoglobin \<80% of the lower limit of normal for Indonesia measured twice).
• Abnormal screening ECG showing prolonged QTc interval (\>450 msec) or any signs of arrythmia/irregularity, ischemia, cardiac enlargement considered considered indicative of acute or chronic cardiovascular disease.

Sponsors & Collaborators

• Congressionally Directed Medical Research Programs: collaborator
• Indonesia University: collaborator
• Sanaria Inc.: lead
• Oxford University Clinical Research Unit Indonesia: collaborator

Study Sites (2)

Department of Internal Medicine, Universitas Indonesia

Jakarta, 10430, Indonesia

Location

Eijkman-Oxford Clinical Research Unit, Eijkman Institute of Molecular Biology

Jakarta, 10430, Indonesia

Location

MeSH Terms

Conditions

Malaria; Malaria, Falciparum

Interventions

Chemoprevention; Saline Solution

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Drug Therapy; Therapeutics; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Limitations and Caveats

Although trial participants were limited to male soldiers, a published meta-analysis of PfSPZ vaccine trials (KC, N et al. "Increased levels of anti-PfCSP antibodies in post-pubertal females....efficacy". Front Immunol. 2022 Oct 25;13:1006716. doi: 10.3389/fimmu.2022.1006716. PMID: 36389797; PMCID: PMC9641621) showed no difference in efficacy between males and females.

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Sanaria Inc.

sanaria@sanaria.com

301-770-3222

Study Officials

• Kevin Baird, Ph.D.

  Eijkman-Oxford Clinical Research Unit, Eijkman Institute of Molecular Biology, Indonesia

  STUDY DIRECTOR

• Erni J Nelwan, MD, Ph.D.

  Department of Internal Medicine, Universitas Indonesia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• 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: April 11, 2018
• First Posted: April 19, 2018
• Study Start: May 7, 2022
• Primary Completion: February 27, 2024
• Study Completion: February 27, 2024
• Last Updated: May 4, 2026
• Results First Posted: May 4, 2026

Record last verified: 2026-03

Locations

ID (2)