Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
DOR/ISL · 8 trials · 3 indications
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who experience an AE through Week 96 will be presented.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who discontinue study intervention due to an AE through Week 96 will be presented.
Plasma HIV-1 RNA quantification will be performed at the central laboratory using a polymerase chain reaction (PCR) assay with a lower limit of detection of \<50 copies/mL.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
HIV-1 RNA levels in blood samples taken at each visit were measured with a reliable lower limit of quantification of \<50 copies/mL. The percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48 is presented using the FDA Snapshot missing data approach.
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE is reported.
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinued study intervention due to an AE is reported.
The Abbott RealTime polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. The percentage of participants with HIV-1 RNA \<50 copies/mL at Week 48 was presented using the Food and Drug Administration (FDA) Snapshot missing data approach. The final analysis for this outcome is presented here.
An AE was any untoward medical occurrence in a study participant administered a study drug, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it is considered related to the study drug. The percentage of participants who experienced at least one AE up to Week 48 was reported. The final analysis for this outcome is presented here.
An AE was any untoward medical occurrence in a study participant administered a study drug, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it is considered related to the study drug. The percentage of participants who discontinued study treatment due to an AE up to Week 48 were reported. The final analysis for this outcome is presented here.
HIV-1 RNA levels in blood samples taken at each visit were measured by the Abbott RealTime polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of 40 copies/mL. The percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48 is presented using the FDA Snapshot missing data approach.
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE was reported.
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinued study intervention due to an AE was reported.
The Abbott RealTime polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. Per protocol, the primary outcome measure, the percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48, is presented using the Food and Drug Administration (FDA) Snapshot missing data approach. The percentage values were rounded to the nearest tenth digit.
The AUC0-24 of ISL in plasma was determined at steady state.
The Cmax of ISL in plasma was determined at steady state.
The Tmax of ISL in plasma was determined at steady state.
The t½ of ISL in plasma was determined at steady state.
The CL/F of ISL from plasma was determined at steady state.
The Vz/F of ISL was determined at steady state.
The AUC0-24 of ISL-TP in PBMCs was determined at steady state.
The Cmax of ISL-TP in PBMCs was determined at steady state.
The C24 of ISL-TP in PBMCs was determined at steady state.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Breast milk samples will be collected to determine the Ae0-24hrs after administration of DOR.
Breast milk samples will be collected to calculate the theoretical daily (24 hour) infant dose of DOR as normalized by participant-reported infant body weight.
Breast milk samples will be collected to calculate the theoretical daily (24 hour) infant dose of DOR relative to the maternal dose.
Breast milk samples will be collected to determine the Ae0-24hrs after administration of total ISL.
Breast milk samples will be collected to calculate the theoretical daily (24 hour) infant dose of ISL as normalized by participant-reported infant body weight.
Breast milk samples will be collected to calculate the theoretical daily (24 hour) infant dose of ISL relative to the maternal dose.
| Arm | Type | Description |
|---|---|---|
| DOR/ISL | EXPERIMENTAL | Participants will receive fixed dose combination (FDC) tablet of DOR/ISL (100 mg/0.25 mg) taken once daily (QD) orally from Day 1 to Week 96. After Week 96, eligible participants may continue on DOR/ISL until week 240 or until DOR/ISL becomes commercially accessible, whichever comes first. |
| BIC/FTC/TAF | ACTIVE_COMPARATOR | Participants take BIC/FTC/TAF and placebo to DOR/ISL qd for 144 weeks. |
| DOR/ISL and Placebo to BIC/FTC/TAF | EXPERIMENTAL | Participants will receive DOR/ISL 100 mg/0.25 mg and Placebo to BIC/FTC/TAF once daily (QD) orally from day 1 to week 144. After week 144, eligible participants may continue on DOR/ISL and continue study treatment until week 240 or to when DOR/ISL becomes commercially accessible (whichever comes first). |
| BIC/FTC/TAF and Placebo to DOR/ISL | ACTIVE_COMPARATOR | Participants will receive BIC/FTC/TAF 50 mg/200 mg/25 mg and Placebo to DOR/ISL once daily (QD) orally from day 1 to week 144. After week 144, eligible participants may switch to DOR/ISL and continue study treatment until week 240 or to when DOR/ISL becomes commercially accessible (whichever comes first). |
| Group 1: doravirine/islatravir (DOR/ISL) | EXPERIMENTAL | Treatment-naïve participants living with human immunodeficiency virus-1 (HIV-1) that had not received ≤10 days of prior antiretroviral therapy received blinded fixed dose combination (FDC) Doravirine/Islatravir (DOR/ISL) (100 mg doravirine \[DOR\]/0.75 mg islatravir \[ISL\]) and placebo to Bictegravir/Tenofovir Alafenamide/Emtricitabine (BIC/FTC/TAF) once daily (QD) from Day 1 to Week 96, and open-label DOR/ISL up to Week 144. At Week 144, participants who consent to enter the optional open-label study extension continued to receive open-label QD FDC of DOR/ISL (100 mg/0.75 mg) for an additional 24 weeks, up to Week 168. |
| Group 2: bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) | ACTIVE_COMPARATOR | Treatment-naïve participants living with HIV-1 that had not received ≤10 days of prior antiretroviral therapy received blinded BIC/FTC/TAF (50 mg bictegravir \[BIC\], 200 mg emtricitabine \[FTC\], 25 mg tenofovir alafenamide \[TAF\]) and placebo to FDC DOR/ISL QD from Day 1 to Week 96, and open-label BIC/FTC/TAF up to Week 144. At Week 144, participants who consent to enter the optional open-label study extension continued to receive QD BIC/FTC/TAF (50 mg/200 mg/25 mg) for an additional 24 weeks, up to Week 168. |
| Group 2: Baseline Antiretroviral Therapy (ART) | ACTIVE_COMPARATOR | Participants received continuous baseline ART for 48 weeks. Continuing participants delayed switch over from baseline ART to DOR/ISL, fixed dose combination of 100 mg DOR/0.75 mg ISL orally once daily, from Week 48 to Week 96, a total DOR/ISL treatment duration of 48 Weeks. |
| Name | Type | Description |
|---|---|---|
| DOR/ISL | DRUG | FDC tablet of 100 mg doravirine (DOR)/0.25 mg islatravir (ISL) taken once daily |
| BIC/FTC/TAF | DRUG | Fixed dose combination tablet containing BIC/FTC/TAF 50 mg/200 mg/25 mg taken by mouth. |
| Placebo to DOR/ISL | DRUG | Placebo tablet matched to DOR/ISL tablet taken by mouth. |
| Placebo to BIC/FTC/TAF | DRUG | Placebo tablet matched to BIC/FTC/TAF tablet taken by mouth. |
| ART | DRUG | Baseline ART regimen will be administered as per approved label. ART medication will not be provided by the Sponsor; participants will provide their own ART medications. Allowed drug classes include nucleoside analog reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), integrase strand transferase inhibitors (InSTIs), fusion inhibitors, chemokine receptor 5 (CCR5) antagonists, post-attachment inhibitor, and pharmacokinetic (PK) boosters. |
| Placebo to FDC DOR/ISL | DRUG | Placebo to FDC DOR/ISL in a single tablet taken orally, once daily |
Inclusion Criteria: * Is currently receiving doravirine/islatravir (DOR/ISL) adult fixed dose combination (FDC) tablet in Merck Sharp \& Dohme (MSD)-sponsored clinical studies (MK-8591A-018, -020, and -033 \[except for heavily treatment-experienced (HTE) participants\]). Exclusion Criteria: * Has...
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DOR/ISL is an investigational small molecule being developed for the treatment of HIV infection and HIV-1 infection. It is being studied in adults who are virologically suppressed on other antiretroviral regimens, as well as in healthy volunteers for certain trials. The drug is currently in Phase 3 clinical development.
DOR/ISL is a combination of doravirine and islatravir. Doravirine is a non-nucleoside reverse transcriptase inhibitor, while islatravir is a nucleoside reverse transcriptase inhibitor. Both target the HIV reverse transcriptase enzyme, which is essential for viral replication.
DOR/ISL is being developed by Merck & Company, Inc., which trades under the ticker symbol MRK. The company is conducting Phase 3 clinical trials to evaluate the safety and efficacy of this combination therapy in people living with HIV.
DOR/ISL is currently in Phase 3 clinical development. It is an investigational drug and has not been approved by regulatory authorities. Multiple Phase 3 trials are ongoing or have been completed to assess its safety and efficacy in treating HIV-1 infection.
DOR/ISL is being studied in several Phase 3 trials, including NCT04223778, NCT04223791, NCT05630755, and NCT05766501. These trials evaluate switching to DOR/ISL in virologically suppressed HIV patients, with some completed and others active but not recruiting. Total enrollment across these studies is approximately 1,956 participants.
Yes, DOR/ISL is also known as DOR/3TC/TDF. This alternative name reflects the combination of doravirine, lamivudine, and tenofovir disoproxil fumarate, which are the components of the drug. The primary name DOR/ISL emphasizes doravirine and islatravir.