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

Seattle Children's Healthcare System

Status and phase

Completed

Phase 1

Conditions

Malaria

Treatments

Biological: GAP3KO

Study type

Interventional

Funder types

Other

Identifiers

NCT02313376

MC-004

Details and patient eligibility

About

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.

Full 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.

Enrollment

10 patients

Sex

All

Ages

18 to 50 years old

Volunteers

Accepts Healthy Volunteers

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