Oral ARV-1801 Given in Combination With Intravenous Ceftazidime or Meropenem for Treatment of Melioidosis in Hospitalized Patients

NCT ID: NCT05105035

Last Updated: 2024-02-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 125 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-14
• Study Completion Date: 2023-10-10

Brief Summary

The study investigates the effect of 14 days of twice daily doses of ARV-1801 or placebo in combination with meropenem or ceftazidime in patients hospitalized with melioidosis.

Detailed Description

ARV-1801 is an oral dosage form and loading dose regimen of sodium fusidate. Sodium fusidate is a member of the fusidane class of antibiotics. Recent evidence demonstrates meaningful activity against multiple biothreat agents, including the intracellular pathogen B. pseudomallei, which causes melioidosis. Once melioidosis is suspected clinically, treatment typically involves intravenous antibiotics such as ceftazidime or meropenem during an initial "intensive" phase (typically 2 weeks) and oral antibiotics such as co trimoxazole during a more chronic "eradication" phase (typically 12 weeks). Nevertheless, mortality can still exceed 40% in some regions, with most deaths occurring early during the eradication phase of therapy.

The purpose of this study is to evaluate the effects of ARV-1801 administered for 14 days in conjunction with the current standard of care (meropenem or ceftazidime) against placebo in conjunction with the current standard of care. Day 1 dosing will include two doses of 1500mg of ARV-1801 or placebo administered 12 hours apart. Days 2-14 will include 600 mg doses of ARV-1801 or placebo administered every 12 hours.

Conditions

Melioidosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo

Patients are administered either IV ceftazidime or IV meropenem per standard of care and placebo. Placebo will be administered every 12 hours for Days 1-14.

Group Type: ACTIVE_COMPARATOR

Ceftazidime or meropenem

Intervention Type: DRUG

Patients will be prescribed ceftazidime or meropenem intravenously as per standard of care for at least 14 days while in the hospital

Placebo

Intervention Type: DRUG

Patients will be prescribed placebo every 12 hours for Days 1-14.

ARV-1801 (ACG-701)

Patients are administered either IV ceftazidime or IV meropenem per standard of care and active ARV-1801. Day 1 dosing will be two doses of 1500mg of ARV-1801 administered 12 hours apart. Days 2-14 dosing will be 600mg of ARV-1801 administered every 12 hours.

Group Type: EXPERIMENTAL

Ceftazidime or meropenem

Intervention Type: DRUG

Patients will be prescribed ceftazidime or meropenem intravenously as per standard of care for at least 14 days while in the hospital

ARV-1801

Intervention Type: DRUG

Patients will be prescribed ARV-1801 at 1500mg 12 hours apart on Day 1 and 600mg every 12 hours for Days 2-14.

Interventions

Ceftazidime or meropenem

Patients will be prescribed ceftazidime or meropenem intravenously as per standard of care for at least 14 days while in the hospital

Intervention Type: DRUG

ARV-1801

Patients will be prescribed ARV-1801 at 1500mg 12 hours apart on Day 1 and 600mg every 12 hours for Days 2-14.

Intervention Type: DRUG

Placebo

Patients will be prescribed placebo every 12 hours for Days 1-14.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Patient must provide written informed consent obtained prior to any study-specific procedure being performed.

2. Patient must be at least 18 years of age or older at time of consent.

3. Patient must be hospitalized with suspected community-acquired melioidosis, meeting at least one of the criteria below:

• History of frequent contact with soil or surface water in an endemic area
• Presence of a known underlying risk factor such as diabetes, renal insufficiency, renal stones or thalassemia
• Special organ involvement such as splenic or hepatic abscess
• An illness compatible with melioidosis, including the presence of sepsis, acute pneumonia, acute pyelonephritis, septic arthritis, parotid disease or skin or soft tissue infection

4. Patient must require intravenous antibiotics i.e., either ceftazidime or meropenem for treatment of suspected melioidosis.

5. Patient must agree to stay in hospital for duration of ARV-1801 therapy, i.e., 14 days.

6. Females of childbearing potential must use an acceptable method of birth control (surgically sterile, intrauterine device, vasectomized partner, oral contraceptive plus barrier contraceptive, hormone delivery system plus barrier contraceptive or condom in combination with contraceptive cream, jelly or foam) for the duration of the study drug administration phase and for 30 days thereafter.

Exclusion Criteria

1. Patient is unable to tolerate oral therapy, either directly or via a nasogastric tube.

2. Patient has a known infection with an identified organism other than B. pseudomallei.

3. Patient is pregnant or lactating.

4. Patient has a known hypersensitivity to sodium fusidate, ceftazidime or meropenem.

5. Patient has been treated with IV antibiotics active against B. pseudomallei (including ceftazidime and meropenem) for longer than 48 hours prior to randomization.

6. Patient requires concomitant treatment with the following:

• OATP1B1 and OATP1B3 substrates, in particular statins (e.g., HMG-CoA reductase inhibitors)
• Medications metabolized by CYP2C8, such as glitazones (e.g., repaglinide)
• CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, phenobarbital, and nafcillin)

7. Patient has had prior treatment with a CYP3A4 inducer, such as dexamethasone, phenytoin, carbamazepine, rifampin, phenobarbital, or nafcillin, within 7 days prior to enrollment.

8. Patient requires treatment with digoxin or warfarin unless a monitoring plan is in place to assess digoxin levels and/or prothrombin time as is relevant.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Arnasi Group

UNKNOWN

Sponsor Role: collaborator

Arrevus Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Maharat Nakhonratchasima Hospital

Nai Muang, , Thailand

Srinagarind Hospital, Khon Kaen University

Nai Muang, , Thailand

Sunpasitthiprasong Hospital

Nai Muang, , Thailand

Surin Hospital

Nai Muang, , Thailand

Udon Thani Hospital

Udon Thani, , Thailand

Countries

Thailand

Other Identifiers

ARV-1801-001

Identifier Type: -

Identifier Source: org_study_id