Safety, Attenuation and Immunogenicity of GAP3KO Administered Via A Stephensi Mosquitoes

Trial to Assess the Safety, Attenuation and Immunogenicity of Genetically-attenuated p52-/p36-/sap1- Plasmodium Falciparum Parasites (GAP3KO) Administered Via Infected Anopheles Stephensi Mosquitoes to Malaria-Naïve Adults

Study designed to evaluate safety and tolerability of a genetically attenuated P. falciparum (GAP3KO) that arrests early in the liver stage of the parasite life cycle. Study will also confirm the attenuation of the GAP3KO parasites using peripheral blood smears. Secondary objectives are to evaluate the humoral immune responses to GAP3KO.

Study Overview

• Status: Completed
• Conditions: Malaria
• Intervention / Treatment: Biological: GAP3KO

Detailed Description

This single arm, open-label, phase 1 safety study is designed to evaluate the safety and tolerability of a genetically attenuated P. falciparum (GAP3KO) that arrests early in the liver stage of the parasite life cycle. The study will also confirm the attenuation of the GAP3KO parasites using peripheral blood smears. The secondary objectives of the study are to evaluate the humoral immune responses to GAP3KO.

A total of 10 healthy, malaria-naïve adult subjects will be enrolled to receive GAP3KO via the bite of 150-200 GAP3K0-infected A. stephensi mosquitoes under controlled conditions. Subjects will be evaluated for safety, reactogenicity, and signs and symptoms of malaria to confirm attenuation for 28 days, including monitoring in a hotel setting 8-18 days post GAP 3KO administration.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Biomedical Research Institute Malaria Clinical Trial Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Good general health
• No hematologic, hepatic, or renal disease
• Weight greater than 50 kg
• Assessment of Understanding completed and passed prior to enrollment
• Availability and reliable access to trial center
• Females must use two forms of pregnancy prevention

Exclusion Criteria:

• Recent (within 6 months) or planned travel to malaria endemic area
• History of confirmed malaria diagnosis

• Anticipated use of the following:

  • Investigational malaria vaccine at any time
  • Malaria chemoprophylaxis within 6 months
  • Chronic systemic immunosuppressive medications within 6 months
  • Blood products or immunoglobulin within 120 days
  • Systemic antibiotics with antimalarial effects within 30 days
  • Investigational product or vaccine within 30 days
  • Live vaccine within 28 days; killed vaccine within 14 days of GAP3KO
  • Medications known to significantly interact with chloroquine or Malarone

• History of:

  • Sickle cell trait or other hemoglobinopathies
  • Splenectomy or functional asplenia
  • Systemic anaphylaxis
  • Severe allergic reaction to mosquito bites or malaria treatment drugs
  • History of chronic or active neurologic disease
  • Cardiac disease or stroke
• Clinically significant medical condition, abnormal lab results
• Clinically significant abnormal ECG
• Moderate or high risk for coronary heart disease
• Acute illness
• Pregnant or nursing female
• HIV, Hepatitis B, or Hepatitis C
• Psychiatric condition that precludes compliance with the protocol
• Suspected or known alcohol or drug abuse
• Staff with direct involvement in conduct of the study or GAP activities

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GAP3KO	Biological: GAP3KO; GAP3KO administered via the bite of 150-200 GAP3KO-infected A. stephensi mosquitoes under controlled conditions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety assessed by frequency of AEs, SAEs, and patent parasitemia via peripheral blood smear	28 Days

Secondary Outcome Measures

Outcome Measure	Time Frame
CSP antibody titer	28 days
Percent inhibition of in vitro sporozoite	28 days

Collaborators and Investigators

• Sponsor: Seattle Children's Research Institute (SCRI)

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Actual): February 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: December 8, 2014
• First Submitted That Met QC Criteria: December 9, 2014
• First Posted (Estimate): December 10, 2014

Study Record Updates

• Last Update Posted (Estimate): November 18, 2015
• Last Update Submitted That Met QC Criteria: November 17, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria
• Other Study ID Numbers: MC-004