To Assess the Safety, Immunogenicity and Efficacy of VLPM01 in Healthy, Malaria-Naïve Volunteers

NCT03867331 | Completed Phase 1 FDA Drug

• 1 other identifier: VLPM01-01 WRAIR #2568
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a proof-of-concept, first in human, Phase I, single center study designed to evaluate the safety, tolerability, immunogenicity and experimental efficacy of VLPM01 in healthy, malaria-naïve adult volunteers. The VLPM01 product will be adjuvanted with alhydrogel. The study design was based on the FDA's guidance "General Principles for the Development of Vaccines to protect Against Global Infectious Diseases" (2011).

Conditions

Malaria,Falciparum

Outcome Measures

Primary Outcomes (5)

• Occurrence of solicited local reactogenicity to VLPM01 at 5, 15 and 30 μg in the 7 days following vaccination

  7 days following vaccination

• Occurrence of solicited systemic reactogenicity to VLPM01 at 5, 15 and 30 μg in the 7 days following vaccination

  7 days following vaccination

• Occurrence of unsolicited adverse events related to VLPM01 at 5, 15 and 30 μg in the 7 days following vaccination

  7 days following vaccination

• Occurrence of adverse events of special interest during follow-up period

  through study completion, an average of 18 months

• Number of participants experiencing any serious adverse event after vaccination.

  through study completion, an average of 18 months

Secondary Outcomes (4)

• Anti-CSP IgG levels measured by ELISA

  day 113 after third dose

• Positive thick blood smear test for P. falciparum malaria following CHMI

  day 6 to day 20 post challenge

• Time to first positive thick blood smear test for P. falciparum following CHMI

  day 6 to day 20 post challenge

• Percentage of participants with a minimum threshold of >20 μg/ml anti-CSP IgG after vaccination as measured by ELISA.

  day 15 to post day 113 after third dose

Study Arms (4)

5 microgram VLPM01

EXPERIMENTAL

5 microgram doses of VLPM01 vaccine, intramuscular administration, n=10

Biological: 5 microgram VLPM01

15 microgram VLPM01

EXPERIMENTAL

15 microgram doses of VLPM01 vaccine, intramuscular administration, n=10

Biological: 15 microgram VLPM01

30 microgram VLPM01

EXPERIMENTAL

30 microgram doses of VLPM01 vaccine, intramuscular administration, n=10

Biological: 30 microgram VLPM01

Controlled Human Malaria Infection (CHMI) Phase

EXPERIMENTAL

Infectivity Control Participants, n=6

Other: Plasmodium falciparum challenge

Interventions

5 microgram VLPM01 BIOLOGICAL

VLPM01 is an alpha-VLP pre-erythrocytic malaria vaccine which targets circumsporozoite protein (CSP), adjuvanted with 0.75 mg alum.

5 microgram VLPM01

15 microgram VLPM01 BIOLOGICAL

VLPM01 is an alpha-VLP pre-erythrocytic malaria vaccine which targets circumsporozoite protein (CSP), adjuvanted with 0.75 mg alum.

15 microgram VLPM01

30 microgram VLPM01 BIOLOGICAL

VLPM01 is an alpha-VLP pre-erythrocytic malaria vaccine which targets circumsporozoite protein (CSP), adjuvanted with 0.75 mg alum.

30 microgram VLPM01

Plasmodium falciparum challenge OTHER

Expose forearms to five (5) Plasmodium falciparum (strain NF54; clone 3D7) bites

Controlled Human Malaria Infection (CHMI) Phase

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adults between the ages 18-49 (inclusive);
• Able and willing to provide written, informed consent;
• Able and willing to comply with all research requirements, in the opinion of the Investigator;
• Agreement to refrain from blood donation during the course of the study. Volunteers who have undergone CHMI can donate to other research once the study is complete but cannot donate to the American Red Cross for at least three (3) years after the CHMI event;
• Laboratory Criteria within 56 days before enrollment:
• Hemoglobin ≥ 11.7 g/dL for women; ≥ 12.0 g/dL for men;
• White Blood Cell count = 3,800-10,800 cells/mm3;
• Platelets = 140,000-400,000/mm3;
• Alanine aminotransferase (ALT; SGPT) 9-46 U/L male and 6-29 U/L female;
• Serum creatinine ≤ 1.5 mg/dL;
• Negative HIV testing (HIV Ab / antigen 4th generation screen with reflex confirmatory RNA testing);
• Negative hepatitis B surface antigen (HBsAg) and hepatitis C antibody testing;
• Birth control requirements:
• Female participants must meet one of the following two (2) criteria:
• No reproductive potential due to post-menopausal status (12 months of natural \[spontaneous\] amenorrhea) or hysterectomy, bilateral oophorectomy or tubal ligation;

You may not qualify if:

• History of malaria infection (any species) or residence in a malaria-endemic area for more than 5 years
• History of serology-confirmed or suspected chikungunya virus (CHIKV) infection;
• Previous travel to malaria endemic regions within the past three (3) months before study enrollment defined as first vaccination or day of challenge (for infectivity controls) or planned travel to malaria endemic regions during the vaccination, CHMI and follow-up period;
• Any history of receiving a malaria vaccine or chikungunya vaccine;
• Received an investigational product in the 30 days before enrollment, or planned to receive during the study period;
• Participation in another clinical research study that would require excessive blood draws in conjunction with this study (as determined by the investigator)
• Receipt of immunoglobulins or blood products within three (3) months before enrollment;
• Any history of anaphylaxis;
• History of sickle cell trait or disease, or any condition that could affect susceptibility to malaria infection, per patient verbal report;
• Pregnancy, lactation or intention to become pregnant during the study;
• History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ);
• History of autoimmune disease;
• Suspected or known current alcohol or drug abuse as defined by an alcohol intake of greater than three (3) drinks a day on average for a man, and greater than two (2) drinks a day on average for a woman for a period of 12 months before enrollment;
• Any medical, psychiatric, social condition, occupational reason or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a volunteer's ability to give informed consent;
• Any clinically significant abnormal finding on chemistry or hematology blood tests or clinical examination, not already specified, as determined by the Investigator;

Sponsors & Collaborators

• VLP Therapeutics: lead

Study Sites (1)

Walter Reed Army Institute of Research

Bethesda, Maryland, 20889, United States

Location

MeSH Terms

Conditions

Malaria, Falciparum

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2019
• First Posted: March 8, 2019
• Study Start: March 13, 2019
• Primary Completion: May 21, 2020
• Study Completion: May 21, 2020
• Last Updated: April 8, 2021

Record last verified: 2021-04

Locations

US (1)