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Trial 051 study design & baseline characteristics

Trial 051 study design

In open-label Trial 051, participants switched from an oral baseline antiretroviral therapy (ART) regimen to IDVYNSO.

A total of 551 participants were randomized (2:1) and switched to once-daily IDVYNSO (n=366) or remained on their baseline ART (n=185). Randomization was stratified by baseline ART.​

Primary efficacy endpoint: Proportion of participants with HIV-1
RNA ≥50 copies/mL at Week 48.

Inclusion criteria

  • Virologically suppressed (HIV-1 RNA <50 copies/mL) adults living with HIV​
  • Stably suppressed on their baseline regimen for at least 
3 months prior to trial entry
  • No history of treatment failure

Exclusion criteria

  • Adults with active HBV infection (HBsAg positive or HBV DNA-positive)

Trial 051 baseline characteristics

Trial 051 (open-label)
IDVYNSO (n=366) vs
Oral Baseline ART (n=185)
Age, mean years (range)50 (18-83)
Race, %

White

Black/African American
Asian

Other/unknown
39

45

5

11
Ethnicity, %

Hispanic/Latino
15
Gender, %
Male
Female
60
40
Mean baseline CD4+ cell count, cells/mm3748
Baseline CD4+ T-cell count >500 cells/mm3, %80
Evidence of past HBV infection,a %~29
Baseline ART at enrollment, %
INSTI-based
PI-based (including combinations with INSTI)
Other
64
5
30

aHepatitis B core antibody positive.

Baseline characteristics were similar between treatment groups

Continue exploring Trial 051

View efficacy data >

Abbreviations

BIC, bictegravir; CD4+, cluster of differentiation 4-positive; FTC, emtricitabine; HBV, hepatitis B virus; INSTI, integrase strand transfer inhibitor; RNA, ribonucleic acid; TAF, tenofovir alafenamide.

INDICATION AND USAGE

IDVYNSO is indicated as a complete two-drug regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults to replace the current antiretroviral regimen in those who are virologically-suppressed (HIV-1 RNA less than 50 copies/mL) on a stable antiretroviral regimen with no history of virologic treatment failure and no known substitutions associated with resistance to doravirine.

SELECTED SAFETY INFORMATION

Contraindications

  • IDVYNSO is contraindicated when co-administered with:
    • drugs that are strong cytochrome P450 (CYP)3A enzyme inducers as significant decreases in doravirine plasma concentrations may occur, which may decrease the effectiveness of IDVYNSO.
    • lamivudine (3TC) or emtricitabine (FTC) as significant decreases in islatravir-triphosphate (ISL-TP) concentrations may occur, which may decrease the effectiveness of IDVYNSO. (See Drug Interactions)

Warnings and Precautions

  • Severe skin reactions, including Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), have been reported during postmarketing experience with doravirine-containing regimens. In addition, Drug Rash with Eosinophilia and Systemic Symptoms (DRESS syndrome) was reported with IDVYNSO in a clinical trial. Discontinue IDVYNSO, and other medications associated with these reactions, immediately if a painful rash with mucosal involvement, a progressive severe rash, or a rash with constitutional symptoms, eosinophilia, lymphadenopathy, or other organ involvement develops. Close clinical monitoring, and appropriate therapy should be initiated.
  • The concomitant use of IDVYNSO and certain other drugs may result in known or potentially significant drug interactions, some of which may lead to loss of therapeutic effect of IDVYNSO and possible development of resistance or possible clinically significant adverse reactions from greater exposures of a component of IDVYNSO.
  • Consider the potential for drug interactions prior to and during IDVYNSO therapy, review concomitant medications during IDVYNSO therapy, and monitor for adverse reactions. (See Drug Interactions)

Adverse Reactions

  • The most common adverse reactions (incidence ≥ 2%, all grades in any treatment group) reported in virologically-suppressed participants in the IDVYNSO treatment groups in Trials 051 and 052, respectively, were: diarrhea (3% and 1%), dizziness (2% and 1%), fatigue (2% and 1%), abdominal distension (2% and 1%), headache (2% and 1%) and weight increased (2% and <1%).
  • The most common adverse reactions (all grades) reported in greater than or equal to 2% of participants in any treatment group in Trials 052 and 051 through Week 48 were as follows:
    • In Trial 052 (IDVYNSO vs BIC/FTC/TAF, respectively): diarrhea (1% vs 1%), dizziness (1% vs 0%), fatigue (1% vs 1%), abdominal distention (1% vs 0%), headache (1% vs 0%), weight increased (less than 1% vs 0%).
    • In Trial 051 (IDVYNSO vs bART, respectively): diarrhea (3% vs 0%), dizziness (2% vs 1%), fatigue (2% vs 1%), abdominal distention (2% vs 0%), headache (2% vs 1%), weight increased (2% vs 0%).
  • A single case of severe immune thrombocytopenia (platelet count nadir of 2 x109/L) characterized by abrupt onset of subcutaneous hematoma, petechiae, and hematuria was reported in a participant 32 days after initiating IDVYNSO. The case resolved with discontinuation of IDVYNSO, in conjunction with treatments including corticosteroids and intravenous immunoglobulin (IVIG). Among all participants in Trials 052 and 051, there were no patterns of platelet decreases over time with IDVYNSO and no differences between treatment arms in mean change from baseline in platelet count.

Drug Interactions

  • IDVYNSO is a complete regimen; co-administration with other antiretroviral medications for treatment of HIV-1 infection is not recommended.
  • Co-administration of IDVYNSO with a CYP3A inducer decreases doravirine plasma concentrations, which may reduce the efficacy of IDVYNSO. If IDVYNSO is co-administered with rifabutin, one tablet of doravirine should be taken approximately 12 hours after the dose of IDVYNSO. Co-administration of IDVYNSO with other moderate CYP3A inducers is not recommended.
  • Co-administration of IDVYNSO and drugs that are inhibitors of CYP3A may result in increased plasma concentrations of doravirine.
  • Co-administration of IDVYNSO is not recommended with deoxycytidine kinase (dCK) substrates (e.g., nucleoside antimetabolites) as they may reduce the exposure of islatravir-triphosphate or with adenosine deaminase (ADA) inhibitors (e.g., pentostatin) as they may increase the exposure of islatravir. (See Contraindications)

Use in Specific Populations

  • Clinical trials in virologically-suppressed participants who received IDVYNSO included 81 (11%) participants aged 65 years and older, including 10 (1%) aged 75 years and older. Overall differences in response have not been identified between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
  • No dosage adjustment of IDVYNSO is required in patients with eGFR ≥30 mL/min/1.73 m2. IDVYNSO is not recommended in patients with eGFR <30 mL/min/1.73 m2 and has not been studied in participants undergoing dialysis.
  • No dosage adjustment of IDVYNSO is recommended in patients with mild or moderate hepatic impairment (Child-Pugh Class A or B). IDVYNSO has not been studied in patients with severe hepatic impairment (Child-Pugh Class C) and therefore is not recommended in these patients.
  • IDVYNSO does not have activity against hepatitis B virus (HBV). Patients with HBV coinfection who switch to IDVYNSO from an antiretroviral regimen with activity against HBV, and patients on IDVYNSO who are newly diagnosed with HBV coinfection, should be closely monitored and specific anti-HBV therapy should be considered, as clinically appropriate.

Dosage and Administration

  • The recommended dosage of IDVYNSO is one tablet taken orally once daily with or without food.
  • If IDVYNSO is co-administered with rifabutin, take one tablet of IDVYNSO once daily as recommended, followed by one tablet of doravirine 100 mg approximately 12 hours after the dose of IDVYNSO for the duration of rifabutin co-administration. Co-administration with other CYP3A inducers is not recommended.

 

 

Before prescribing IDVYNSOTM (doravirine/islatravir), please read the accompanying Prescribing Information. The Patient Information also is available.

INDICATION AND USAGE
SELECTED SAFETY INFORMATION

IDVYNSO is indicated as a complete two-drug regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults to replace the current antiretroviral regimen in those who are virologically-suppressed (HIV-1 RNA less than 50 copies/mL) on a stable antiretroviral regimen with no history of virologic treatment failure and no known substitutions associated with resistance to doravirine.

SELECTED SAFETY INFORMATION

Contraindications

  • IDVYNSO is contraindicated when co-administered with:
    • drugs that are strong cytochrome P450 (CYP)3A enzyme inducers as significant decreases in doravirine plasma concentrations may occur, which may decrease the effectiveness of IDVYNSO.
    • lamivudine (3TC) or emtricitabine (FTC) as significant decreases in islatravir-triphosphate (ISL-TP) concentrations may occur, which may decrease the effectiveness of IDVYNSO. (See Drug Interactions)

Warnings and Precautions

  • Severe skin reactions, including Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), have been reported during postmarketing experience with doravirine-containing regimens. In addition, Drug Rash with Eosinophilia and Systemic Symptoms (DRESS syndrome) was reported with IDVYNSO in a clinical trial. Discontinue IDVYNSO, and other medications associated with these reactions, immediately if a painful rash with mucosal involvement, a progressive severe rash, or a rash with constitutional symptoms, eosinophilia, lymphadenopathy, or other organ involvement develops. Close clinical monitoring, and appropriate therapy should be initiated.
  • The concomitant use of IDVYNSO and certain other drugs may result in known or potentially significant drug interactions, some of which may lead to loss of therapeutic effect of IDVYNSO and possible development of resistance or possible clinically significant adverse reactions from greater exposures of a component of IDVYNSO.
  • Consider the potential for drug interactions prior to and during IDVYNSO therapy, review concomitant medications during IDVYNSO therapy, and monitor for adverse reactions. (See Drug Interactions)

Adverse Reactions

  • The most common adverse reactions (incidence ≥ 2%, all grades in any treatment group) reported in virologically-suppressed participants in the IDVYNSO treatment groups in Trials 051 and 052, respectively, were: diarrhea (3% and 1%), dizziness (2% and 1%), fatigue (2% and 1%), abdominal distension (2% and 1%), headache (2% and 1%) and weight increased (2% and <1%).
  • The most common adverse reactions (all grades) reported in greater than or equal to 2% of participants in any treatment group in Trials 052 and 051 through Week 48 were as follows:
    • In Trial 052 (IDVYNSO vs BIC/FTC/TAF, respectively): diarrhea (1% vs 1%), dizziness (1% vs 0%), fatigue (1% vs 1%), abdominal distention (1% vs 0%), headache (1% vs 0%), weight increased (less than 1% vs 0%).
    • In Trial 051 (IDVYNSO vs bART, respectively): diarrhea (3% vs 0%), dizziness (2% vs 1%), fatigue (2% vs 1%), abdominal distention (2% vs 0%), headache (2% vs 1%), weight increased (2% vs 0%).
  • A single case of severe immune thrombocytopenia (platelet count nadir of 2 x109/L) characterized by abrupt onset of subcutaneous hematoma, petechiae, and hematuria was reported in a participant 32 days after initiating IDVYNSO. The case resolved with discontinuation of IDVYNSO, in conjunction with treatments including corticosteroids and intravenous immunoglobulin (IVIG). Among all participants in Trials 052 and 051, there were no patterns of platelet decreases over time with IDVYNSO and no differences between treatment arms in mean change from baseline in platelet count.

Drug Interactions

  • IDVYNSO is a complete regimen; co-administration with other antiretroviral medications for treatment of HIV-1 infection is not recommended.
  • Co-administration of IDVYNSO with a CYP3A inducer decreases doravirine plasma concentrations, which may reduce the efficacy of IDVYNSO. If IDVYNSO is co-administered with rifabutin, one tablet of doravirine should be taken approximately 12 hours after the dose of IDVYNSO. Co-administration of IDVYNSO with other moderate CYP3A inducers is not recommended.
  • Co-administration of IDVYNSO and drugs that are inhibitors of CYP3A may result in increased plasma concentrations of doravirine.
  • Co-administration of IDVYNSO is not recommended with deoxycytidine kinase (dCK) substrates (e.g., nucleoside antimetabolites) as they may reduce the exposure of islatravir-triphosphate or with adenosine deaminase (ADA) inhibitors (e.g., pentostatin) as they may increase the exposure of islatravir. (See Contraindications)

Use in Specific Populations

  • Clinical trials in virologically-suppressed participants who received IDVYNSO included 81 (11%) participants aged 65 years and older, including 10 (1%) aged 75 years and older. Overall differences in response have not been identified between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
  • No dosage adjustment of IDVYNSO is required in patients with eGFR ≥30 mL/min/1.73 m2. IDVYNSO is not recommended in patients with eGFR <30 mL/min/1.73 m2 and has not been studied in participants undergoing dialysis.
  • No dosage adjustment of IDVYNSO is recommended in patients with mild or moderate hepatic impairment (Child-Pugh Class A or B). IDVYNSO has not been studied in patients with severe hepatic impairment (Child-Pugh Class C) and therefore is not recommended in these patients.
  • IDVYNSO does not have activity against hepatitis B virus (HBV). Patients with HBV coinfection who switch to IDVYNSO from an antiretroviral regimen with activity against HBV, and patients on IDVYNSO who are newly diagnosed with HBV coinfection, should be closely monitored and specific anti-HBV therapy should be considered, as clinically appropriate.

Dosage and Administration

  • The recommended dosage of IDVYNSO is one tablet taken orally once daily with or without food.
  • If IDVYNSO is co-administered with rifabutin, take one tablet of IDVYNSO once daily as recommended, followed by one tablet of doravirine 100 mg approximately 12 hours after the dose of IDVYNSO for the duration of rifabutin co-administration. Co-administration with other CYP3A inducers is not recommended.

 

 

Before prescribing IDVYNSOTM (doravirine/islatravir), please read the accompanying Prescribing Information. The Patient Information also is available.