Safety and Efficacy of Sanaria's PfSPZ-CVac in Malian Adults

November 27, 2019 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

Safety, Tolerability, Immunogenicity and Protective Efficacy Against Naturally-Transmitted Malaria of Infectious, Cryopreserved Plasmodium Falciparum Sporozoites (PfSPZ Challenge) Administered by Direct Venous Inoculation Under Chloroquine Chemoprophylaxis (PfSPZ-CVac), in Malian Adults: A Randomized, Double Blind, Placebo-Controlled Trial

Single site, double-blinded, randomized, placebo-controlled clinical trial of PfSPZ-CVac safety, tolerability, immunogenicity and efficacy against naturally occurring malaria in malaria-exposed Malian adults. The overall goal of the study is to evaluate if a regimen of PfSPZ-CVac (PfSPZ Challenge under chemoprophylaxis) is safe, well-tolerated, and provides sterile protection against naturally-occurring malaria in malaria-experienced adults. The study population includes 62 healthy, malaria-experienced adults aged 18-45 years, inclusive, residing in Bougoula Hameau and surrounding villages, Mali. The primary objective of this study is to assess the safety and tolerability of PfSPZ Challenge compared to placebo among malaria-experienced adults taking chloroquine prophylaxis (PfSPZ-CVac)

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a single site, double-blinded, randomized, placebo-controlled clinical trial of PfSPZ-CVac safety, tolerability, immunogenicity and efficacy against naturally occurring malaria in malaria-exposed Malian adults. The overall goal of the study is to evaluate if a regimen of PfSPZ-CVac (PfSPZ Challenge under chemoprophylaxis) is safe, well-tolerated, and provides sterile protection against naturally-occurring malaria in malaria-experienced adults. Participants will receive three immunizing PfSPZ Challenge injections via direct venous inoculation (DVI) four weeks apart under chloroquine chemoprophylaxis. The PfSPZ Challenge dose will be 204,800 PfSPZ. This is based on results of studies in Europe and in Africa. In Tübingen, Germany, 100% of malaria-naïve adults who received three doses of 51,200 PfSPZ every four weeks under chloroquine chemoprophylaxis were protected against homologous controlled human malaria infection (CHMI). At the same time, studies of PfSPZ Vaccine in malaria-experienced adults in Mali and in Tanzania demonstrate that higher doses of PfSPZ are required to demonstrate immunogenicity and high grade protection in malaria-experienced adults that is comparable to that achieved in malaria-naïve adults studied in the USA. For this reason, the dose selected for this study is four-fold higher than the dose used for Tübingen, Germany. Controls will receive 0.9% sodium chloride (NaCl) as placebo. All participants will receive a standard chemoprophylactic regimen of chloroquine (CQ) for 10 weeks. Chloroquine will be given as a loading dose (600mg chloroquine base) two days before the first administration of PfSPZ Challenge, followed by weekly doses of chloroquine (300mg chloroquine base weekly). Participants will also be treated with a 7-day regimen of artesunate (200 mg per day) after the last PfSPZ Challenge dose of 204,800 sporozoites for malaria parasite clearance, one week after the last CQ dose is given. A total of 62 participants will be randomized in a 1:1 ratio to one of two groups and will be inoculated with PfSPZ Challenge or 0.9% NaCl by DVI so that a total of 62 adults will participate in the study. Participants will be recruited from the MRTC's Bougoula-Hameau site. All volunteers recruited will be healthy adults aged between 18 and 45 years. Safety and infectivity data will be collected. Volunteers, clinical and laboratory investigators will be blinded to group allocation. Participants will be followed every four weeks after the last vaccination as outpatients for active malaria diagnosis and treatment. Passive follow-up will be accomplished by continuous availability of study staff onsite to diagnose and treat malaria and other medical issues that arise. The primary objective of this study is to assess the safety and tolerability of PfSPZ Challenge compared to placebo among malaria-experienced adults taking chloroquine prophylaxis (PfSPZ-CVac). The secondary objectives are: 1. to assess the protective efficacy of PfSPZ-CVac against naturally transmitted P. falciparum malaria infection as diagnosed by thick blood smear microscopy, 2. To assess protective efficacy of PfSPZ-CVac against naturally transmitted P. falciparum malaria infection as diagnosed by qPCR, 3. to assess the expanded efficacy of PfSPZ-CVac compared to placebo, and 4. to examine the immune response to P. falciparum malaria infection.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
62

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Mali
      • Sikasso, Mali
        • University of Bamako - Epidemiology of Parasitic Diseases - Malaria Research and Training Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 41 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. A male or non-pregnant female aged 18-45 years inclusive at the time of screening.

  2. For women of childbearing potential, willingness not to become pregnant or breastfeed until one month after the last CQ dose*.

    *Pre-menopausal female participants will be referred to the local family planning clinic, which offers several means of contraception that are approved and recommended by the Mali Ministry of Health. Contraception (male or female condoms, diaphragm or cervical cap with spermicide, intrauterine device, or hormone-based contraceptive) should be started 30 days before the first vaccination and continue until 30 days after last vaccination.

  3. Written informed consent obtained from the participant before screening.
  4. Available and willing to participate in follow-up for the duration of study.
  5. Residing in Bougoula Hameau region and environs.
  6. In general good health based on clinical and laboratory investigation.

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 immunosuppressants 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. Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days before the first study vaccination with the exception of tetanus toxoid.
  5. Confirmed or suspected immunosuppressive or immunodeficient condition.
  6. Confirmed or suspected autoimmune disease.
  7. History of allergic reactions or anaphylaxis to chloroquine, 4-aminoquinolone derivatives, artesunate and artemisinin derivatives, vaccinations or to any vaccine component.
  8. History of serious allergic reactions to any substance, requiring hospitalization or emergent medical care.
  9. History of allergy to any component of the PfSPZ Challenge product, including 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. Confirmed pregnancy.
  13. Laboratory evidence of liver disease (ALT > upper limit of normal).
  14. Laboratory evidence of renal disease (serum or plasma creatinine > upper limit of normal).
  15. Laboratory evidence of hematologic disease (platelet count <114,000/mm^3 for males and <144,000/mm^3 for females, or hemoglobin <11.2 g/dL for males and <9.5 g/dL for females).
  16. Seropositive for hepatitis B surface antigen or hepatitis C virus (hepatitis C antibody).
  17. Seropositive for HIV.
  18. Sickle cell trait carriage or sickle cell disease.
  19. Administration of immunoglobulin and/or any blood products within the three months preceding the first study. vaccination or planned administration during the study period.
  20. Simultaneous participation in any other interventional clinical trial.

  21. 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 PI.

  22. Has evidence of increased cardiovascular disease risk (defined as > 10 percent, 5 year risk) as determined by the method of Gaziano*.

    *Risk factors include sex, age (years), systolic blood pressure (mm Hg), smoking status, body mass index (BMI, kg/mm^2), reported diabetes status, and blood pressure.

  23. Abnormal screening ECG*.

    *Pathologic Q wave and significant ST-T wave changes, left ventricular hypertrophy, non-sinus rhythm except isolated premature atrial or ventricular contractions, right or left bundle branch block, advanced A-V heart block (secondary or tertiary), QT/QTc interval >450 ms.

  24. Other condition that in the opinion of the PI would jeopardize the safety or rights of a participant in the trial or would render the participant unable to comply with the protocol.
  25. Documented history of non-febrile seizures or atypical (complex) febrile seizures.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 204,800 PfSPZ of PfSPZ Challenge
204,800 PfSPZ of PfSPZ Challenge every 4 weeks x 3 doses by DVI, n=31
Biological: PfSPZ (NF54) Challenge
Cryopreserved Plasmodium falciparum (Pf) fully infectious sporozoites (SPZ) that have been developed to be used to infect volunteers in controlled human malaria infection (CHMI) to assess the efficacy of antimalarial drugs and vaccines. The PfSPZ (NF54) Challenge contains a laboratory malaria strain isolated from a Dutch traveler to Africa.
Drug: Artesunate
Artesunate is a succinic ester of artemether.
Drug: Chloroquine
4-aminoquinolone, antimalarial agent for oral administration
Placebo Comparator: NaCl placebo
NaCl placebo every 4 weeks x 3 doses by DVI, n=31
Other: Placebo
Placebo
Biological: PfSPZ (NF54) Challenge
Cryopreserved Plasmodium falciparum (Pf) fully infectious sporozoites (SPZ) that have been developed to be used to infect volunteers in controlled human malaria infection (CHMI) to assess the efficacy of antimalarial drugs and vaccines. The PfSPZ (NF54) Challenge contains a laboratory malaria strain isolated from a Dutch traveler to Africa.
Drug: Artesunate
Artesunate is a succinic ester of artemether.
Drug: Chloroquine
4-aminoquinolone, antimalarial agent for oral administration

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
The number of serious adverse events (SAEs)
Time Frame: 45 days
45 days
The number of solicited local and systemic adverse events (AE)
Time Frame: Day 12 after vaccination
Day 12 after vaccination
The number of unsolicited AEs related to study product
Time Frame: Day 12 after vaccination
Day 12 after vaccination
The severity of solicited local and systemic adverse events (AE)
Time Frame: Day 12 after vaccination
Day 12 after vaccination
The severity of unsolicited AEs related to study product
Time Frame: Day 12 after vaccination
Day 12 after vaccination

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Antibody titers against P. falciparum circumsporozoite protein (CSP) and other P. falciparum proteins at serology time points
Time Frame: Days 3, 15, 31, 43,59, 71-77,87,245,and 413
Days 3, 15, 31, 43,59, 71-77,87,245,and 413
Markers of cell-mediated immunity as assessed by cells producing interferon gamma and/or IL-2
Time Frame: Days 3, 15, 31, 43,59, 71-77,87,245,and 413
Days 3, 15, 31, 43,59, 71-77,87,245,and 413
Time to P. falciparum parasitemia, detected by qPCR
Time Frame: within six months after the last vaccination
within six months after the last vaccination
Time to P. falciparum parasitemia, detected by qPCR
Time Frame: within twelve months after the last vaccination
within twelve months after the last vaccination
Time to P. falciparum parasitemia, detected by thick blood film microscopy
Time Frame: within twelve months after the last vaccination
within twelve months after the last vaccination
Time to P. falciparum parasitemia, detected by thick blood smear microscopy
Time Frame: Within six months after the last vaccination
Within six months after the last vaccination

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
National Institute of Allergy and Infectious Diseases (NIAID)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 6, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 22, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 22, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 15, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 15, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 19, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 2, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 27, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 19, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 15-0052
  • HHSN272201300022I

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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