NCT03278808

Chloroquine (CQ) and Azithromycin (AZ) Combination for Malaria Prophylaxis

A Phase 2a Open Label Study of the Safety and Efficacy of a Single Dose of Weekly Chloroquine (CQ) and Azithromycin (AZ) Administered in Combination for Malaria Prophylaxis in Healthy Adults Challenged With 7G8 Chloroquine-Resistant Plasmodium Falciparum in a Controlled Human Malaria Infection (CHMI) Model

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: U.S. Army Medical Research and Development Command · Federal
• Sex: All
• Age: 18 Years – 50 Years
• Healthy volunteers: Accepted

Summary

This is an open label, Phase 2 study with controlled human malaria infection (CHMI). Twenty three subjects will be enrolled into 2 groups (15 subjects in the Chloroquine-Azithromycin \[CQ/AZ\] Intervention Group, and 8 subjects in the Chloroquine \[CQ\] Group). The CQ/AZ Group will receive experimental intervention of 300 mg of CQ and 2 g of azithromycin (AZ). The CQ Group will receive 300 mg of CQ only. All subjects will participate in the CHMI and will be required to stay at a hotel for evaluation for a maximum of 14 nights starting 7 days after the challenge. A standard dose of atovaquone-proguanil (Malarone®) will be administered to all symptomatic parasitemic subjects under directly observed treatment.

Detailed description

This study is a Phase 2, open-label study of the combination of a single dose-level of AZ (Zithromax) plus CQ given weekly as a prophylaxis against CQ-resistant P falciparum in healthy adults. After signing informed consent, subjects will undergo screening procedures between Day -77 to Day -18. If enrolled, subjects who are still eligible at Study Day -18 will be randomized to either the CQ/AZ group (Group 1 of 15 subjects: 2 g AZ (Zithromax) plus 300 mg CQ base weekly for 6 weeks), or the CQ control group (Group 2 of 8 subjects: 300 mg chloroquine base weekly for 6 weeks) and start intervention on Study Day -17. The rationale for the CQ control group to receive CQ is to show that the strain utilized (7G8) is indeed chloroquine resistant in humans: we expect all of the subjects in the CQ control group to become symptomatically parasitemic. If 3 or more subjects in the CQ control group do not become symptomatic with malaria, the CHMI will be considered uncontrolled either due to 7G8 not being CQ-resistant, or the parasite not being infective.

Conditions

• Malaria

Interventions

Type	Name	Description
DRUG	Chloroquine-Azithromycin (CQ/AZ)	Chloroquine-Azithromycin (CQ/AZ); Chloroquine (CQ) 300mg and 2g of azithromycin (AZ) given orally
DRUG	Chloroquine (CQ)	Chloroquine (CQ); 300 mg of CQ only given orally
DRUG	atovaquone-proguanil (Malarone®)	All subjects will participate in the Controlled Human Malaria Infection (CHMI) and will be required to stay at a hotel for evaluation for a maximum of 14 nights starting 7 days after the challenge. A standard dose of atovaquone-proguanil (Malarone®) will be administered to all symptomatic parasitemic subjects under directly observed treatment.

Timeline

• Start date: 2018-09-17
• Primary completion: 2019-12-30
• Completion: 2020-01-01
• First posted: 2017-09-12
• Last updated: 2020-02-27

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study