MelioidosisPhase 2NCT05105035
Oral ARV-1801 Given in Combination With Intravenous Ceftazidime or Meropenem for Treatment of Melioidosis in Hospitalized Patients
A Phase 2 study testing Ceftazidime or meropenem and ARV-1801 in people with Melioidosis, run by Arrevus Inc. at 5 sites in Thailand.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melioidosis
- What is being tested?
- Ceftazidime or meropenem and ARV-1801
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 125 participants
- Where
- 5 sitesThailand
- Study dates
- 14 Jun 2022to 10 Oct 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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:
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- 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.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Thailand5 sites
Maharat Nakhonratchasima Hospital
Nai Muang
Srinagarind Hospital, Khon Kaen University
Nai Muang
Sunpasitthiprasong Hospital
Nai Muang
Surin Hospital
Nai Muang
Udon Thani Hospital
Udon Thani, 41000
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled, Exploratory Study to Assess the Efficacy, Safety and Tolerability of Oral ARV-1801 Given in Combination With Intravenous Ceftazidime or Meropenem for Intensive Phase Therapy of Melioidosis in Hospitalized Patients
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.
Read the 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
- Being tested
- Ceftazidime or meropenem, ARV-1801, Placebo
- Keywords
- meropenem, ceftazidime, B. pseudomallei
- Medical subject headings
- Melioidosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ceftazidime or meropenemDrug
Patients will be prescribed ceftazidime or meropenem intravenously as per standard of care for at least 14 days while in the hospital
ARV-1801Drug
Patients will be prescribed ARV-1801 at 1500mg 12 hours apart on Day 1 and 600mg every 12 hours for Days 2-14.
PlaceboDrug
Patients will be prescribed placebo every 12 hours for Days 1-14.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Ceftazidime or meropenem; Drug: ARV-1801 |
What is being measured
The primary outcome is the main question the study is designed to answer.
All-cause in-hospital mortality through Day 14 in the modified intent-to-treat population (mITT)
Measured: Measured at Day 14
Secondary outcomes (9)
All-cause in-hospital mortality in mITT population
Measured: 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: Measured at study completion, on average 28 days (assessed up to 60 days)
All-cause in-hospital mortality in the ITT population
Measured: 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: Measured at Days 1, 3 and 7
Number of days in the ICU in the mITT population
Measured: Measured at study completion, on average 28 days (assessed up to 60 days)
Number of days on ventilator in the mITT population
Measured: Measured at study completion, on average 28 days (assessed up to 60 days)
Length of hospital stay in the mITT population
Measured: Measured at study completion, on average 28 days (assessed up to 60 days)
Melioidosis seriousness score in mITT population
Measured: Measured at Day 28
Number of patients experiencing adverse events
Measured: Measured at study completion, on average 28 days (assessed up to 60 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2021
- Study start14 Jun 2022
- Primary completion10 Oct 2023
- Study completion10 Oct 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MelioidosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 125 participants (actual)
Sponsor and investigators
- Lead sponsor
- Arrevus Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Arnasi Group
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05105035
- Sponsor's protocol ID
- ARV-1801-001
- Status last verified
- Feb 2024
- First submitted
- 23 Sep 2021
- Last updated
- 16 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled, Exploratory Study to Assess the Efficacy, Safety and Tolerability of Oral ARV-1801 Given in Combination With Intravenous Ceftazidime or Meropenem for Intensive Phase Therapy of Melioidosis in Hospitalized Patients
- ClinicalTrials.gov ID
- NCT05105035
- Acronym / sponsor ID
- ARV-1801-001
- Conditions
- Melioidosis
- Keywords
- meropenem, ceftazidime, B. pseudomallei
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 125 participants (actual)
- Lead sponsor
- Arrevus Inc.Industry (pharma, biotech, devices)
- Collaborators
- Arnasi Group
- Study start
- 14 Jun 2022 (actual)
- Primary completion
- 10 Oct 2023 (actual)
- Study completion
- 10 Oct 2023 (actual)
- First posted
- 3 Nov 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Active comparator | Drug: Ceftazidime or meropenem, Drug: PlaceboPatients 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. |
| ARV-1801 (ACG-701) | Experimental | Drug: Ceftazidime or meropenem, Drug: ARV-1801Patients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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:
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ceftazidime or meropenemPatients will be prescribed ceftazidime or meropenem intravenously as per standard of care for at least 14 days while in the hospital | Drug | ARV-1801 (ACG-701), Placebo |
| ARV-1801Patients will be prescribed ARV-1801 at 1500mg 12 hours apart on Day 1 and 600mg every 12 hours for Days 2-14. | Drug | ARV-1801 (ACG-701) |
| PlaceboPatients will be prescribed placebo every 12 hours for Days 1-14. | Drug | Placebo |
Primary outcome
All-cause in-hospital mortality through Day 14 in the modified intent-to-treat population (mITT)
Time frame: Measured at Day 14
9 secondary outcomes
All-cause in-hospital mortality in mITT population
Time frame: 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
Time frame: Measured at study completion, on average 28 days (assessed up to 60 days)
All-cause in-hospital mortality in the ITT population
Time frame: 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
Time frame: Measured at Days 1, 3 and 7
Number of days in the ICU in the mITT population
Time frame: Measured at study completion, on average 28 days (assessed up to 60 days)
Number of days on ventilator in the mITT population
Time frame: Measured at study completion, on average 28 days (assessed up to 60 days)
Length of hospital stay in the mITT population
Time frame: Measured at study completion, on average 28 days (assessed up to 60 days)
Melioidosis seriousness score in mITT population
Time frame: Measured at Day 28
Number of patients experiencing adverse events
Time frame: Measured at study completion, on average 28 days (assessed up to 60 days)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Feb 2024.
- Individual participant dataSharing planned: No
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Dengue, Chikungunya
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ceftazidime or meropenem and ARV-1801 in people with Melioidosis, run by Arrevus Inc. at 5 sites in Thailand.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Thailand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
All-cause in-hospital mortality through Day 14 in the modified intent-to-treat population (mITT) (time frame: Measured at Day 14). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Feb 2024.