HIV-1 Infection
Conditions
Brief summary
The primary objectives of this study are to evaluate the antiretroviral activity and the safety/tolerability of open-label doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF; MK-1439A; DELSTRIGO™) consisting of a single fixed-dose combination (FDC) tablet of DOR/3TC/TDF 100 mg/300 mg/300 mg in treatment-naïve HIV-1 infected participants with select non-nucleoside reverse transcriptase inhibitor (NNRTI) transmitted resistance-associated mutations.
Detailed description
This study had a Base Study (Day 1 to Week 96) and an optional Study Extension (Week 96 to Week 192).
Interventions
FDC tablet containing MK-1439 (doravirine) 100 mg / lamivudine 300 mg / tenofovir disoproxil fumarate 300 mg taken by mouth.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Is HIV-1 positive within 45 days prior to the treatment phase of this study, and have HIV treatment indicated based on physician assessment. * Is naïve to antiretroviral therapy (ART) including investigational antiretroviral agents. * Prior to screening, have had a genotype performed confirming the presence of only one of the following NNRTI mutations: K103N, Y181C, or G190A. * Is considered clinically stable with no signs or symptoms of active infection at time of entry into the study (i.e. clinical status and all chronic medications should be unchanged for at least 2 weeks prior to the start of treatment in this study). * Is highly unlikely to become pregnant or to impregnate a partner
Exclusion criteria
* Is a user of recreational or illicit drugs or has had a recent history of drug or alcohol abuse or dependence. * Has been treated for a viral infection other than HIV-1, such as hepatitis B, with an agent that is active against HIV-1, including, but not limited to, adefovir, tenofovir, entecavir, emtricitabine, or lamivudine. * Has documented or known resistance to study drugs (doravirine, lamivudine, and/or tenofovir) * Has participated or anticipates participating in a study with an investigational compound/device within 30 days prior to signing informed consent * Has any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids, tumor necrosis factor (TNF) antagonists, or other immunosuppressant drugs during the course of the trial. * Requires or anticipates requiring any of the prohibited medications * Has significant hypersensitivity or other contraindication to any of the components of the study drug * Has a current (active) diagnosis of acute hepatitis due to any cause * Has evidence of decompensated liver disease or has liver cirrhosis and a Child-Pugh Class C score or Pugh-Turcotte (CPT) score \> 9 * Is pregnant, breastfeeding, or expecting to conceive * Is female and expecting to donate eggs, or is male and is expecting to donate sperm at any time during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Experiencing ≥1 Adverse Events (AE) up to Week 96 | Up to Week 96 | The percentage of participants experiencing ≥1 AE up to Week 96 was calculated. An AE was defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy could be determined. |
| Percentage of Participants Who Discontinued Treatment Due to an AE up to Week 48. | Up to Week 48 | The percentage of participants who discontinued from study medication due to an adverse event was calculated. An AE was defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy could be determined. |
| Percentage of Participants Who Discontinued Treatment Due to an AE up to Week 96 | Up to Week 96 | The percentage of participants who discontinued from study medication due to an adverse event was calculated. An AE was defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy could be determined. |
| Percentage of Participants Achieving HIV-1 Ribonucleic Acid (RNA) <50 Copies/mL of Plasma at Week 48 | Week 48 | The percentage of participants achieving HIV-1 ribonucleic acid (RNA) \<50 copies/mL in plasma at Week 48 was calculated. The Abbott RealTime HIV-1 Assay, which has a lower limit of reliable quantification (LoQ) of 40 copies/mL, was used to measure the HIV-1 RNA level in plasma samples obtained at Week 48 visit. |
| Percentage of Participants Experiencing ≥1 Adverse Events (AE) up to Week 48 | Up to Week 48 | The percentage of participants experiencing ≥1 AE up to Week 48 was calculated. An AE was defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy could be determined. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Loss of Virologic Response | Up to Week 96 | The time to loss of virologic response (TLOVR) was reported. For participants who achieved HIV-1 RNA \<50 copies/mL of plasma and subsequently had two consecutive HIV-1 RNA values of ≥50 copies/mL measured at least 1 week apart, TLOVR was the time between Day 1 and the date of the first of the two consecutive values ≥50 copies/mL. For participants who achieved and sustained HIV-1 RNA \<50 copies/mL, time to loss of virologic response was censored at the time of the last available measurement. |
| Change From Baseline in CD4 Cell Count at Week 96 | Baseline (Day 1) and Week 96 | The change from baseline in CD4 cell count at Week 96 was calculated. |
| Percentage of Participants Achieving HIV-1 Ribonucleic Acid (RNA) <50 Copies/mL of Plasma at Week 96 | Week 96 | The percentage of participants achieving HIV-1 ribonucleic acid (RNA) \<50 copies/mL in plasma at Week 96 was calculated. The Abbott RealTime HIV-1 Assay, which has a lower limit of reliable quantification (LoQ) of 40 copies/mL, was used to measure the HIV-1 RNA level in plasma samples obtained at Week 96 visit. |
| Percentage of Participants Achieving HIV-1 Ribonucleic Acid (RNA) <40 Copies/mL of Plasma at Week 48 | Week 48 | The percentage of participants achieving HIV-1 ribonucleic acid (RNA) \<40 copies/mL in plasma at Week 48 was calculated. The Abbott RealTime HIV-1 Assay, which has a lower limit of reliable quantification (LoQ) of 40 copies/mL, was used to measure the HIV-1 RNA level in plasma samples obtained at Week 48 visit. Participants with reading below the LoQ were considered to have \<40 copies/mL. |
| Percentage of Participants Achieving HIV-1 Ribonucleic Acid (RNA) <40 Copies/mL of Plasma at Week 96 | Week 96 | The percentage of participants achieving HIV-1 ribonucleic acid (RNA) \<40 copies/mL in plasma at Week 96 was calculated. The Abbott RealTime HIV-1 Assay, which has a lower limit of reliable quantification (LoQ) of 40 copies/mL, was used to measure the HIV-1 RNA level in plasma samples obtained at Week 96 visit. Participants with reading below the LoQ were considered to have \<40 copies/mL. |
| Change From Baseline in CD4 Cell Count at Week 48 | Baseline (Day 1) and Week 48 | The change from baseline in CD4 cell count at Week 48 was calculated. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving HIV-1 Ribonucleic Acid (RNA) <50 Copies/mL of Plasma at Week 192 | Week 192 | The percentage of participants achieving HIV-1 ribonucleic acid (RNA) \<50 copies/mL in plasma at Week 192 was calculated. The Abbott RealTime HIV-1 Assay, which has a lower limit of reliable quantification (LoQ) of 40 copies/mL, was used to measure the HIV-1 RNA level in plasma samples obtained at Week 192 visit. |
| Change From Baseline in CD4 Cell Count at Week 192 | Baseline (Day 1) and Week 192 | The change from baseline in CD4 cell count at Week 192 was calculated. |
| Percentage of Participants Achieving HIV-1 Ribonucleic Acid (RNA) <40 Copies/mL of Plasma at Week 192 | Week 192 | The percentage of participants achieving HIV-1 ribonucleic acid (RNA) \<40 copies/mL in plasma at Week 192 was calculated. The Abbott RealTime HIV-1 Assay, which has a lower limit of reliable quantification (LoQ) of 40 copies/mL, was used to measure the HIV-1 RNA level in plasma samples obtained at Week 192 visit. Participants with reading below the LoQ were considered to have \<40 copies/mL. |
Participant flow
Recruitment details
Participants were enrolled at 7 study sites in Canada, France, Spain, UK, and USA.
Participants by arm
| Arm | Count |
|---|---|
| DOR/3TC/TDF Treatment-naïve HIV-1 infected participants with NNRTI transmitted resistance-associated mutations were treated with open-label MK-1439A (DOR/3TC/TDF 100mg/300mg/300mg) as a FDC tablet taken once daily by mouth for 96 weeks in the Base Study. In addition, eligible participants continued to receive the same MK-1439A regimen from Week 96 to Week 192 during the optional Extension Study. | 10 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Base Study | Lost to Follow-up | 2 |
| Base Study | Non-Compliance With Study Drug | 1 |
| Extension Study | Adverse Event | 1 |
| Extension Study | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | DOR/3TC/TDF |
|---|---|
| Age, Continuous | 37.1 Years STANDARD_DEVIATION 32.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 6 |
| other Total, other adverse events | 9 / 10 | 5 / 6 |
| serious Total, serious adverse events | 1 / 10 | 0 / 6 |
Outcome results
Primary
Percentage of Participants Achieving HIV-1 Ribonucleic Acid (RNA) <50 Copies/mL of Plasma at Week 48
The percentage of participants achieving HIV-1 ribonucleic acid (RNA) \<50 copies/mL in plasma at Week 48 was calculated. The Abbott RealTime HIV-1 Assay, which has a lower limit of reliable quantification (LoQ) of 40 copies/mL, was used to measure the HIV-1 RNA level in plasma samples obtained at Week 48 visit.
Time frame: Week 48
Population: All participants who received ≥1 dose of MK-1439A, had baseline and Week 48 data for HIV in plasma, and whose central lab results confirmed the presence of protocol-specified NNRTI transmitted resistance-associated mutations.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DOR/3TC/TDF | Percentage of Participants Achieving HIV-1 Ribonucleic Acid (RNA) <50 Copies/mL of Plasma at Week 48 | 100.0 Percentage of Participants |
Primary
Percentage of Participants Experiencing ≥1 Adverse Events (AE) up to Week 48
The percentage of participants experiencing ≥1 AE up to Week 48 was calculated. An AE was defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy could be determined.
Time frame: Up to Week 48
Population: All participants who received ≥1 dose of MK-1439A.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DOR/3TC/TDF | Percentage of Participants Experiencing ≥1 Adverse Events (AE) up to Week 48 | 90.0 Percentage of Participants |
Primary
Percentage of Participants Experiencing ≥1 Adverse Events (AE) up to Week 96
The percentage of participants experiencing ≥1 AE up to Week 96 was calculated. An AE was defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy could be determined.
Time frame: Up to Week 96
Population: All participants who received ≥1 dose of MK-1439A.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DOR/3TC/TDF | Percentage of Participants Experiencing ≥1 Adverse Events (AE) up to Week 96 | 90.0 Percentage of Participants |
Primary
Percentage of Participants Who Discontinued Treatment Due to an AE up to Week 48.
The percentage of participants who discontinued from study medication due to an adverse event was calculated. An AE was defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy could be determined.
Time frame: Up to Week 48
Population: All participants who received ≥1 dose of MK-1439A.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DOR/3TC/TDF | Percentage of Participants Who Discontinued Treatment Due to an AE up to Week 48. | 0.0 Percentage of Participants |
Primary
Percentage of Participants Who Discontinued Treatment Due to an AE up to Week 96
The percentage of participants who discontinued from study medication due to an adverse event was calculated. An AE was defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy could be determined.
Time frame: Up to Week 96
Population: All participants who received ≥1 dose of MK-1439A.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DOR/3TC/TDF | Percentage of Participants Who Discontinued Treatment Due to an AE up to Week 96 | 0.0 Percentage of Participants |
Secondary
Change From Baseline in CD4 Cell Count at Week 48
The change from baseline in CD4 cell count at Week 48 was calculated.
Time frame: Baseline (Day 1) and Week 48
Population: All participants who received ≥1 dose of MK-1439A, had baseline and Week 48 data for CD4 cell count, and whose central lab results confirmed the presence of protocol-specified NNRTI transmitted resistance-associated mutations.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| DOR/3TC/TDF | Change From Baseline in CD4 Cell Count at Week 48 | Baseline for the Week 48 Population | 409 Cells/mm^3 |
| DOR/3TC/TDF | Change From Baseline in CD4 Cell Count at Week 48 | Change from Baseline at Week 48 | 132 Cells/mm^3 |
Secondary
Change From Baseline in CD4 Cell Count at Week 96
The change from baseline in CD4 cell count at Week 96 was calculated.
Time frame: Baseline (Day 1) and Week 96
Population: All participants who received ≥1 dose of MK-1439A, had baseline and Week 96 data for CD4 cell count, and whose central lab results confirmed the presence of protocol-specified NNRTI transmitted resistance-associated mutations.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| DOR/3TC/TDF | Change From Baseline in CD4 Cell Count at Week 96 | Baseline for the Week 96 Population | 437 Cells/mm^3 |
| DOR/3TC/TDF | Change From Baseline in CD4 Cell Count at Week 96 | Change from Baseline at Week 96 | 153 Cells/mm^3 |
Secondary
Percentage of Participants Achieving HIV-1 Ribonucleic Acid (RNA) <40 Copies/mL of Plasma at Week 48
The percentage of participants achieving HIV-1 ribonucleic acid (RNA) \<40 copies/mL in plasma at Week 48 was calculated. The Abbott RealTime HIV-1 Assay, which has a lower limit of reliable quantification (LoQ) of 40 copies/mL, was used to measure the HIV-1 RNA level in plasma samples obtained at Week 48 visit. Participants with reading below the LoQ were considered to have \<40 copies/mL.
Time frame: Week 48
Population: All participants who received ≥1 dose of MK-1439A, had baseline and Week 48 data for HIV in plasma, and whose central lab results confirmed the presence of protocol-specified NNRTI transmitted resistance-associated mutations.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DOR/3TC/TDF | Percentage of Participants Achieving HIV-1 Ribonucleic Acid (RNA) <40 Copies/mL of Plasma at Week 48 | 100.0 Percentage of Participants |
Secondary
Percentage of Participants Achieving HIV-1 Ribonucleic Acid (RNA) <40 Copies/mL of Plasma at Week 96
The percentage of participants achieving HIV-1 ribonucleic acid (RNA) \<40 copies/mL in plasma at Week 96 was calculated. The Abbott RealTime HIV-1 Assay, which has a lower limit of reliable quantification (LoQ) of 40 copies/mL, was used to measure the HIV-1 RNA level in plasma samples obtained at Week 96 visit. Participants with reading below the LoQ were considered to have \<40 copies/mL.
Time frame: Week 96
Population: All participants who received ≥1 dose of MK-1439A, had baseline and Week 96 data for HIV in plasma, and whose central lab results confirmed the presence of protocol-specified NNRTI transmitted resistance-associated mutations.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DOR/3TC/TDF | Percentage of Participants Achieving HIV-1 Ribonucleic Acid (RNA) <40 Copies/mL of Plasma at Week 96 | 100.0 Percentage of Participants |
Secondary
Percentage of Participants Achieving HIV-1 Ribonucleic Acid (RNA) <50 Copies/mL of Plasma at Week 96
The percentage of participants achieving HIV-1 ribonucleic acid (RNA) \<50 copies/mL in plasma at Week 96 was calculated. The Abbott RealTime HIV-1 Assay, which has a lower limit of reliable quantification (LoQ) of 40 copies/mL, was used to measure the HIV-1 RNA level in plasma samples obtained at Week 96 visit.
Time frame: Week 96
Population: All participants who received ≥1 dose of MK-1439A, had baseline and Week 96 data for HIV in plasma, and whose central lab results confirmed the presence of protocol-specified NNRTI transmitted resistance-associated mutations.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DOR/3TC/TDF | Percentage of Participants Achieving HIV-1 Ribonucleic Acid (RNA) <50 Copies/mL of Plasma at Week 96 | 100.0 Percentage of Participants |
Secondary
Time to Loss of Virologic Response
The time to loss of virologic response (TLOVR) was reported. For participants who achieved HIV-1 RNA \<50 copies/mL of plasma and subsequently had two consecutive HIV-1 RNA values of ≥50 copies/mL measured at least 1 week apart, TLOVR was the time between Day 1 and the date of the first of the two consecutive values ≥50 copies/mL. For participants who achieved and sustained HIV-1 RNA \<50 copies/mL, time to loss of virologic response was censored at the time of the last available measurement.
Time frame: Up to Week 96
Population: All participants who experienced protocol-defined virologic failure, received ≥1 dose of MK-1439A, had baseline and later data for HIV in plasma, and whose central lab results confirmed the presence of protocol-specified NNRTI transmitted resistance-associated mutations. Participants who did not experience virologic failure were excluded from the analysis population.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| DOR/3TC/TDF | Time to Loss of Virologic Response | 166 Days |
Other Pre-specified
Change From Baseline in CD4 Cell Count at Week 192
The change from baseline in CD4 cell count at Week 192 was calculated.
Time frame: Baseline (Day 1) and Week 192
Population: All participants who received ≥1 dose of MK-1439A, had baseline and Week 192 data for CD4 cell count, and whose central lab results confirmed the presence of protocol-specified NNRTI transmitted resistance-associated mutations.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| DOR/3TC/TDF | Change From Baseline in CD4 Cell Count at Week 192 | Baseline for the Week 192 Population | 479 Cells/mm^3 |
| DOR/3TC/TDF | Change From Baseline in CD4 Cell Count at Week 192 | Change from Baseline at Week 192 | 196 Cells/mm^3 |
Other Pre-specified
Percentage of Participants Achieving HIV-1 Ribonucleic Acid (RNA) <40 Copies/mL of Plasma at Week 192
The percentage of participants achieving HIV-1 ribonucleic acid (RNA) \<40 copies/mL in plasma at Week 192 was calculated. The Abbott RealTime HIV-1 Assay, which has a lower limit of reliable quantification (LoQ) of 40 copies/mL, was used to measure the HIV-1 RNA level in plasma samples obtained at Week 192 visit. Participants with reading below the LoQ were considered to have \<40 copies/mL.
Time frame: Week 192
Population: All participants who received ≥1 dose of MK-1439A, had baseline and Week 192 data for HIV in plasma, and whose central lab results confirmed the presence of protocol-specified NNRTI transmitted resistance-associated mutations.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DOR/3TC/TDF | Percentage of Participants Achieving HIV-1 Ribonucleic Acid (RNA) <40 Copies/mL of Plasma at Week 192 | 100.0 Percentage of Participants |
Other Pre-specified
Percentage of Participants Achieving HIV-1 Ribonucleic Acid (RNA) <50 Copies/mL of Plasma at Week 192
The percentage of participants achieving HIV-1 ribonucleic acid (RNA) \<50 copies/mL in plasma at Week 192 was calculated. The Abbott RealTime HIV-1 Assay, which has a lower limit of reliable quantification (LoQ) of 40 copies/mL, was used to measure the HIV-1 RNA level in plasma samples obtained at Week 192 visit.
Time frame: Week 192
Population: All participants who received ≥1 dose of MK-1439A, had baseline and Week 192 data for HIV in plasma, and whose central lab results confirmed the presence of protocol-specified NNRTI transmitted resistance-associated mutations.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DOR/3TC/TDF | Percentage of Participants Achieving HIV-1 Ribonucleic Acid (RNA) <50 Copies/mL of Plasma at Week 192 | 100.0 Percentage of Participants |