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

NCT05105035 | Completed Phase 2 FDA Drug

• 1 other identifier: ARV-1801-001
• Study Type: interventional
• Target: 125
• Locations: 1 country
• Sites: 5

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.

Conditions

Melioidosis

Keywords

meropenem; ceftazidime; B. pseudomallei

Outcome Measures

Primary Outcomes (1)

• All-cause in-hospital mortality through Day 14 in the modified intent-to-treat population (mITT)

  Measured at Day 14

Secondary Outcomes (9)

• All-cause in-hospital mortality in mITT population

  Measured at study completion, on average 28 days (assessed up to 60 days)

• All-cause in-hospital mortality through Day 14 in the ITT population

  Measured at study completion, on average 28 days (assessed up to 60 days)

• All-cause in-hospital mortality in the ITT population

  Measured at study completion, on average 28 days (assessed up to 60 days)

• Clearance of positive baseline B. pseudomallei blood cultures at Day 1, 3 and 7

  Measured at Days 1, 3 and 7

• Number of days in the ICU in the mITT population

  Measured at study completion, on average 28 days (assessed up to 60 days)

Study Arms (2)

Placebo

ACTIVE COMPARATOR

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.

Drug: Ceftazidime or meropenem; Drug: Placebo

ARV-1801 (ACG-701)

EXPERIMENTAL

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.

Drug: Ceftazidime or meropenem; Drug: ARV-1801

Interventions

Ceftazidime or meropenem 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 (ACG-701); Placebo

ARV-1801 DRUG

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

ARV-1801 (ACG-701)

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must provide written informed consent obtained prior to any study-specific procedure being performed.
• Patient must be at least 18 years of age or older at time of consent.
• 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
• Patient must require intravenous antibiotics i.e., either ceftazidime or meropenem for treatment of suspected melioidosis.
• Patient must agree to stay in hospital for duration of ARV-1801 therapy, i.e., 14 days.
• 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.

You may not qualify if:

• Patient is unable to tolerate oral therapy, either directly or via a nasogastric tube.
• Patient has a known infection with an identified organism other than B. pseudomallei.
• Patient is pregnant or lactating.
• Patient has a known hypersensitivity to sodium fusidate, ceftazidime or meropenem.
• Patient has been treated with IV antibiotics active against B. pseudomallei (including ceftazidime and meropenem) for longer than 48 hours prior to randomization.
• 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)
• Patient has had prior treatment with a CYP3A4 inducer, such as dexamethasone, phenytoin, carbamazepine, rifampin, phenobarbital, or nafcillin, within 7 days prior to enrollment.
• 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.

Sponsors & Collaborators

• Arrevus Inc.: lead
• Arnasi Group: collaborator

Study Sites (5)

Maharat Nakhonratchasima Hospital

Nai Muang, Thailand

Location

Srinagarind Hospital, Khon Kaen University

Nai Muang, Thailand

Location

Sunpasitthiprasong Hospital

Nai Muang, Thailand

Location

Surin Hospital

Nai Muang, Thailand

Location

Udon Thani Hospital

Udon Thani, 41000, Thailand

Location

MeSH Terms

Conditions

Melioidosis

Interventions

Ceftazidime; Meropenem

Condition Hierarchy (Ancestors)

Burkholderia Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Cephaloridine; Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Thienamycins; Carbapenems

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Active study drug and placebo will appear the same to study staff and patients. Bottles will be blinded to study staff and patients.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2021
• First Posted: November 3, 2021
• Study Start: June 14, 2022
• Primary Completion: October 10, 2023
• Study Completion: October 10, 2023
• Last Updated: February 16, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

TH (5)