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

Malaria Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02313376
• Other study ID #: MC-004
• Status: Completed
• Phase: Phase 1
• First received: December 8, 2014
• Last updated: November 17, 2015
• Start date: December 2014
• Est. completion date: August 2015

Study information

• Verified date: November 2015
• Source: Seattle Biomedical Research Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: August 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

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 Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Malaria

Intervention

Biological:
• GAP3KO
GAP3KO administered via the bite of 150-200 GAP3KO-infected A. stephensi mosquitoes under controlled conditions.

Locations

Country	Name	City	State
United States	Seattle Biomedical Research Institute Malaria Clinical Trial Center	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Seattle Biomedical Research Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety assessed by frequency of AEs, SAEs, and patent parasitemia via peripheral blood smear		28 Days	Yes
Secondary	CSP antibody titer		28 days	No
Secondary	Percent inhibition of in vitro sporozoite		28 days	No