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

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ClinicalTrials.gov Identifier: NCT03503058
Recruitment Status : Not yet recruiting
First Posted : April 19, 2018
Last Update Posted : October 16, 2018
Sponsor:
Collaborators:
Eijkman Oxford Clinical Research Unit, Eijkman Institute
Indonesia University
Congressionally Directed Medical Research Programs
Information provided by (Responsible Party):
Sanaria Inc.

Brief Summary:
The study is a single site, double-blind, randomized, placebo-controlled clinical trial that will assess the safety, tolerability, immunogenicity and vaccine efficacy (VE) of PfSPZ Vaccine and PfSPZ-CVac against naturally occurring malaria in Indonesian soldiers deployed to eastern Indonesia.

Condition or disease Intervention/treatment Phase
Malaria Biological: PfSPZ Vaccine Biological: PfSPZ Challenge under chloroquine (CQ) chemoprophylaxis Other: Normal Saline Phase 2

Detailed Description:

The study is a single site, double-blind, randomized, placebo-controlled clinical trial that will assess the safety, tolerability, immunogenicity and vaccine efficacy of PfSPZ Vaccine and PfSPZ-CVac against naturally occurring malaria in Indonesian soldiers. A total of 420 participants will be randomized 1.0:0.5:1.0:0.5 to 4 groups. Participants will be recruited from an Indonesian army battalion based in a malaria-free area. All volunteers will be healthy males aged 18 to 55 years. They will be immunized in a malaria-free area of Indonesia, and then deployed to eastern Indonesia for ~6-9 months. Standard safety, tolerability, and parasitology data will be collected before deployment during the immunization period.

Participants will receive three doses by DVI of

  1. PfSPZ Vaccine on days 1, 8, and 29,
  2. PfSPZ Challenge with chloroquine (CQ) prophylaxis on days 1, 29, and 57,
  3. normal saline (NS) on days 1, 8, and 29, or
  4. normal saline with CQ prophylaxis on days 1, 29, and 57. The PfSPZ Vaccine dose will be 9 x 10^5 PfSPZ. The PfSPZ Challenge dose will be 2 x 10^5 PfSPZ. CQ will first be given as a loading dose of 600 mg base two days before the first administration of PfSPZ Challenge or NS, followed by weekly 300 mg doses of CQ with the last dose 5 days after the last dose of PfSPZ Challenge.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 420 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: 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
Estimated Study Start Date : March 2019
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria

Arm Intervention/treatment
Experimental: Group 1
N=140 will receive PfSPZ Vaccine; three doses of 9x10^5 PfSPZ of PfSPZ Vaccine administered by direct venous inoculation (DVI) given at 0, 7 and 28 day intervals.
Biological: PfSPZ Vaccine
Radiation-attenuated, aseptic, purified, cryopreserved Plasmodium falciparum sporozoites (PfSPZ Vaccine)

Placebo Comparator: Group 2
N=70 will receive normal saline; three doses of NS administered by DVI given at 0, 7 and 28 day intervals.
Other: Normal Saline
0.9% Sodium chloride
Other Name: NS

Experimental: Group 3

N=140 will receive PfSPZ Challenge under chloroquine (CQ) chemoprophylaxis; three doses of 2x10^5 PfSPZ of PfSPZ Challenge administered by DVI at 0, 28 and 56 day intervals (or 0, 4 and 8 week intervals), with weekly CQ.

CQ will first be given as a loading dose of 600 mg base two days before the first administration of PfSPZ Challenge, followed by weekly 300 mg doses of CQ with the last dose 5 days after the last dose of PfSPZ Challenge.

Biological: PfSPZ Challenge under chloroquine (CQ) chemoprophylaxis
Infectious, aseptic, purified, cryopreserved Plasmodium falciparum sporozoites (PfSPZ Challenge) administered under CQ chemoprophylaxis
Other Name: PfSPZ-CVac

Placebo Comparator: Group 4

N=70 will receive normal; three doses of NS administered by DVI given at 0, 28 and 56 day intervals (or 0, 4 and 8 week intervals), with weekly CQ.

CQ will first be given as a loading dose of 600 mg base two days before the first administration of NS, followed by weekly 300 mg doses of CQ with the last dose 5 days after the last dose of NS.

Other: Normal Saline
0.9% Sodium chloride
Other Name: NS




Primary Outcome Measures :
  1. The number of adverse events occurring after vaccination and placebo administration [ Time Frame: a. From day of immunization until end of study (24 months). b. 7 days (PfSPZ Vaccine) or 12 (first two doses) or 14 (third dose) days (PfSPZ-CVac) of each administration. c. 28 days of each administration ]
    1. The number of serious adverse events (SAEs) related to vaccination or placebo administration during active participation in the trial.
    2. The number and severity of solicited AEs occurring within 7 days (PfSPZ Vaccine) or 12 (first two doses) or 14 (third dose) days (PfSPZ-CVac) of each administration of investigational product (IP) related to vaccination or placebo administration.
    3. The number and severity of unsolicited AEs occurring within 28 days of each administration of investigational product (IP) related to vaccination or placebo administration.

  2. The number of microscopy-confirmed first infections with Pf [ Time Frame: 6 to 9 months ]
    The number of microscopy-confirmed first infections with Pf among subjects receiving vaccine vs. placebo during the period from 10 days after arriving in eastern Indonesia through 10 days after leaving eastern Indonesia.


Secondary Outcome Measures :
  1. The number of microscopy confirmed first infections with Pv in eastern Indonesia [ Time Frame: 6 to 9 months ]
    The number of microscopy confirmed first infections with Pv among subjects receiving vaccine vs. placebo during the period from 10 days after arriving in eastern Indonesia through 10 days after leaving eastern Indonesia.

  2. The number of microscopy confirmed first infections with Pv after leaving eastern Indonesia [ Time Frame: 6 months ]
    The number of microscopy confirmed first infections with Pv among subjects receiving vaccine vs. placebo for 6 months post-exposure beginning 10 days after leaving eastern Indonesia.

  3. The number of PCR-confirmed first infections [ Time Frame: a. 6-9 months; b. 6-9 months; c. 6 months ]
    1. With Pf among subjects receiving vaccine vs. placebo during the period from 10 days after arriving in eastern Indonesia through 10 days after leaving eastern Indonesia.
    2. With Pv among subjects receiving vaccine vs. placebo during the period from 10 days after arriving in eastern Indonesia through 10 days after leaving eastern Indonesia.
    3. With Pv among subjects receiving vaccine vs. placebo for 6 months post-exposure and beginning 10 days after leaving eastern Indonesia.

  4. The immune responses induced by vaccination compared to those induced by placebo administration [ Time Frame: 2 weeks after third dose of vaccine ]
    1. Levels of antibodies against Pf circumsporozoite protein (CSP) and PfSPZ 2 weeks after the third dose of vaccine in protected vs. unprotected subjects
    2. Levels of antibodies against PvCSP and PvSPZ 2 weeks after the third dose of vaccine in protected vs. unprotected subjects
    3. Levels of antibodies against other Pf proteins, and Pf asexual erythrocytic stages (AES) 2 weeks after the third dose, and at other time points, if protective efficacy is considered to be significant
    4. Levels of antibodies against other Pv proteins, and Pv asexual erythrocytic stages (AES) 2 weeks after the third dose, and at other time points, if protective efficacy is considered to be significant
    5. Cellular immune responses against PfSPZ and/or PfAES 2 weeks after the third dose of vaccine, if protective efficacy is considered to be significant

  5. Associations between immune responses and protection among subjects receiving vaccine vs. placebo during the period from 10 days after arriving in eastern Indonesia through 10 days after leaving eastern Indonesia. [ Time Frame: Period spanning 10 days after arrival through 10 days following departure from Indonesia ]
  6. Associations between immune responses measured prior to the 24-week period of surveillance beginning after return to Java and the risk of relapse during that period. [ Time Frame: 24 week-period beginning after return to Java ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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 and a body mass index (BMI) ≤35 kg/m^2.

Exclusion Criteria:

  • 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.
  • Planned administration of 3 or more vaccines not foreseen by the study protocol within 28 days before the first study vaccination and for 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 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 considered by a cardiologist to be indicative or acute or chronic cardiovascular disease.
  • 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.
  • Administration of immunoglobulin and/or any blood products within the three months preceding the first study vaccination or planned administration during the study period.
  • Simultaneous participation in any other interventional clinical trial.
  • 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.
  • Any evidence of active malaria, whether symptomatic or asymptomatic, confirmed by RDT, microscopy or PCR less than 3 weeks before first injection of PfSPZ Vaccine or PfSPZ-CVac.
  • History of non-febrile seizures or atypical febrile seizures.
  • Under treatment for tuberculosis.
  • Subjects with > 5% 5-year cardiovascular risk (fatal and non-fatal) based on the Gaziano scoring system; subjects in the 18-34 year old age group will be assessed as though they are in the 35-44 age group.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03503058


Contacts
Contact: Kevin Baird, Ph.D. +62-21-391-0414 kbaird@eocru.org
Contact: Erni J Nelwan, MD, Ph.D. +62-21-391-4190 ejnelwan@yahoo.com

Locations
Indonesia
Department of Internal Medicine, Universitas Indonesia Not yet recruiting
Jakarta, Indonesia, 10430
Eijkman-Oxford Clinical Research Unit, Eijkman Institute of Molecular Biology Not yet recruiting
Jakarta, Indonesia, 10430
Contact: Kevin Baird, Ph.D.         
Sponsors and Collaborators
Sanaria Inc.
Eijkman Oxford Clinical Research Unit, Eijkman Institute
Indonesia University
Congressionally Directed Medical Research Programs
Investigators
Study Director: Kevin Baird, Ph.D. Eijkman-Oxford Clinical Research Unit, Eijkman Institute of Molecular Biology, Indonesia
Principal Investigator: Erni J Nelwan, MD, Ph.D. Department of Internal Medicine, Universitas Indonesia

Responsible Party: Sanaria Inc.
ClinicalTrials.gov Identifier: NCT03503058     History of Changes
Other Study ID Numbers: IDSPZV1
First Posted: April 19, 2018    Key Record Dates
Last Update Posted: October 16, 2018
Last Verified: October 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sanaria Inc.:
Plasmodium falciparum
Sporozoites
PfSPZ

Additional relevant MeSH terms:
Parasitic Diseases
Malaria
Protozoan Infections
Vaccines
Chloroquine
Chloroquine diphosphate
Immunologic Factors
Physiological Effects of Drugs
Amebicides
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Antimalarials
Antirheumatic Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-Inflammatory Agents
Filaricides
Antinematodal Agents
Anthelmintics