Dengue Fever
Conditions
Keywords
Dengue, Vector borne disease, Infections, Virus disease, Viral, RNA virus, Hemorrhagic fevers
Brief summary
The Phase 2 study will be conducted in adult patients with confirmed Dengue infection and will investigate safety, PK, and pharmacodynamics (PD) in this population. The study will be conducted in several dosing cohorts to enable dose selection for subsequent trials
Interventions
DRUGAT-752
AT-752 for 5 days
DRUGPlacebo
Placebo for 5 days
Sponsors
Atea Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Eligible subjects will be randomized to receive either AT-752 or matching placebo orally 3 times a day (TID) for 5 days in Cohort 1 of the study. Subsequent cohorts will receive AT-752/placebo either twice a day (BID) or TID
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * 18-55 years of age at time of screening * Fever ≥38°C (or feeling feverish) with onset during the previous 48 hours * Live/work in or recent travel to dengue endemic area * Positive test confirming Dengue (DENV) on a NS1 antigen test or reverse transcription-polymerase chain reaction (RT-PCR) assay * Negative rapid diagnostic test result for Coronavirus (SARS-CoV-2) and Influenza A and B Key
Exclusion criteria
* Pregnant, plans to become pregnant within 90 days of screening, or breast feeding. * Has previously received any investigational or approved vaccine for dengue * Previous history of HIV, chronic hepatitis B infection, or current hepatitis C infection (from medical history) * Use of any antiviral drug within 30 days or within 5 half-lives of the active drug or metabolite (for long-acting antivirals) * Current use of anticoagulant or antiplatelet drugs or documented medical history of bleeding disorders * Current use of medications for treatment of inflammatory bowel disease or documented medical history of chronic gastrointestinal disease including inflammatory bowel disease * Immunocompromised due to use of immunosuppressive drugs including systemic corticosteroids (inhaled or topical corticosteroids are allowed) or any current disease or condition * Evidence of severe dengue disease * Confirmed or suspected Coronavirus (SARS-CoV-2) infection or contact with patients with confirmed SARS-CoV2 infection within 7 days prior to screening * Other clinically significant medical conditions or laboratory abnormalities, as described in the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Dengue (DENV) Viral Load From Baseline | Baseline, Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 14, Day 28 | To investigate the antiviral activity of AT-752 versus placebo in terms of reduction of DENV RNA from baseline in adult subjects with confirmed DENV infection |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic (PK) Endpoint | Day 3: 0, 0.5, 1, 2, 4, 6 hours post-dose | Maximum plasma concentration (Cmax) of AT-281 |
Countries
Brazil, Colombia, Ecuador, India, Malaysia, Peru, Philippines, Taiwan, Thailand, Vietnam
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AT-752 750-mg TID for 5 Days Tablet; 750-mg, Three (3) times a day for 5-days
AT-752: AT-752 for 5 days | 14 |
| Placebo TID for 5 Days Tablet; Placebo, Three (3) times a day for 5-days
Placebo: Placebo for 5 days | 7 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo TID for 5 Days | AT-752 750-mg TID for 5 Days | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 14 Participants | 21 Participants |
| Age, Continuous | 28.0 years STANDARD_DEVIATION 5.54 | 31.1 years STANDARD_DEVIATION 8.53 | 30.1 years STANDARD_DEVIATION 7.67 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 7 Participants | 14 Participants | 21 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment India | 3 participants | 7 participants | 10 participants |
| Region of Enrollment Philippines | 2 participants | 2 participants | 4 participants |
| Region of Enrollment Thailand | 2 participants | 5 participants | 7 participants |
| Sex: Female, Male Female | 3 Participants | 8 Participants | 11 Participants |
| Sex: Female, Male Male | 4 Participants | 6 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 7 |
| other Total, other adverse events | 10 / 14 | 6 / 7 |
| serious Total, serious adverse events | 1 / 14 | 1 / 7 |
Outcome results
Primary
Change in Dengue (DENV) Viral Load From Baseline
To investigate the antiviral activity of AT-752 versus placebo in terms of reduction of DENV RNA from baseline in adult subjects with confirmed DENV infection
Time frame: Baseline, Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 14, Day 28
Population: Number of subjects with available viral load for baseline and the particular post-baseline timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AT-752 750-mg TID for 5 Days | Change in Dengue (DENV) Viral Load From Baseline | Baseline Viral Load | 5.8 log10 copies/mL | Standard Deviation 2 |
| AT-752 750-mg TID for 5 Days | Change in Dengue (DENV) Viral Load From Baseline | Day 5 | -3.3 log10 copies/mL | Standard Deviation 1.8 |
| AT-752 750-mg TID for 5 Days | Change in Dengue (DENV) Viral Load From Baseline | Day 3 | -2.8 log10 copies/mL | Standard Deviation 1.3 |
| AT-752 750-mg TID for 5 Days | Change in Dengue (DENV) Viral Load From Baseline | Day 6 | -3.3 log10 copies/mL | Standard Deviation 1.8 |
| AT-752 750-mg TID for 5 Days | Change in Dengue (DENV) Viral Load From Baseline | Day 2 | -1.3 log10 copies/mL | Standard Deviation 1.1 |
| AT-752 750-mg TID for 5 Days | Change in Dengue (DENV) Viral Load From Baseline | Day 8 | -3.4 log10 copies/mL | Standard Deviation 1.8 |
| AT-752 750-mg TID for 5 Days | Change in Dengue (DENV) Viral Load From Baseline | Day 4 | -3.3 log10 copies/mL | Standard Deviation 1.8 |
| AT-752 750-mg TID for 5 Days | Change in Dengue (DENV) Viral Load From Baseline | Day 14 | -3.3 log10 copies/mL | Standard Deviation 1.9 |
| AT-752 750-mg TID for 5 Days | Change in Dengue (DENV) Viral Load From Baseline | Day 28 | -3.4 log10 copies/mL | Standard Deviation 1.8 |
| Placebo TID for 5 Days | Change in Dengue (DENV) Viral Load From Baseline | Day 14 | -1.9 log10 copies/mL | Standard Deviation 2.5 |
| Placebo TID for 5 Days | Change in Dengue (DENV) Viral Load From Baseline | Day 28 | -1.9 log10 copies/mL | Standard Deviation 2.5 |
| Placebo TID for 5 Days | Change in Dengue (DENV) Viral Load From Baseline | Baseline Viral Load | 4.6 log10 copies/mL | Standard Deviation 2.5 |
| Placebo TID for 5 Days | Change in Dengue (DENV) Viral Load From Baseline | Day 2 | -0.8 log10 copies/mL | Standard Deviation 0.9 |
| Placebo TID for 5 Days | Change in Dengue (DENV) Viral Load From Baseline | Day 3 | -1.2 log10 copies/mL | Standard Deviation 1.3 |
| Placebo TID for 5 Days | Change in Dengue (DENV) Viral Load From Baseline | Day 4 | -1.2 log10 copies/mL | Standard Deviation 1.7 |
| Placebo TID for 5 Days | Change in Dengue (DENV) Viral Load From Baseline | Day 5 | -1.8 log10 copies/mL | Standard Deviation 2.6 |
| Placebo TID for 5 Days | Change in Dengue (DENV) Viral Load From Baseline | Day 6 | -1.9 log10 copies/mL | Standard Deviation 2.5 |
| Placebo TID for 5 Days | Change in Dengue (DENV) Viral Load From Baseline | Day 8 | -1.9 log10 copies/mL | Standard Deviation 2.5 |
p-value: <0.95ANCOVA
Secondary
Pharmacokinetic (PK) Endpoint
Maximum plasma concentration (Cmax) of AT-281
Time frame: Day 3: 0, 0.5, 1, 2, 4, 6 hours post-dose
Population: PK Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AT-752 750-mg TID for 5 Days | Pharmacokinetic (PK) Endpoint | 2390 ng/mL | Standard Deviation 2460 |
Secondary
Pharmacokinetic (PK) Endpoint
Area under the concentration-time curve (AUCtau) of AT-281
Time frame: Day 3: 0, 0.5, 1, 2, 4, 6 hours post-dose
Population: PK Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AT-752 750-mg TID for 5 Days | Pharmacokinetic (PK) Endpoint | 4270 h*ng/mL | Standard Deviation 2750 |