Bictegravir/Emtricitabine/Tenofovir Alafenide Plus Doravirine

An Open Label Study Evaluating the Safety and Efficacy of Switching From Rilpivirine/Emtricitabine/Tenofovir Alafenamide in Combination With Dolutegravir, to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Combination With Doravirine, in Male HIV+ Subjects > 45 Years With Multi-drug Resistant Virus and Virologic Suppression (Documented With at Least One Viral Load Result < 50 Copies Per mL) During the Last 6 Months on Current Therapy

The current study proposal is an open label observational trial for maintenance of virologic suppression, and is designed as a non- inferiority switch trial. The study will involve approximately 30 patients, which includes a PK arm of approximately 10 patients. The study will also include secondary outcomes of quality of life (QOL) and weight changes

Hypothesis:

Patients with prior NUC or NNRTI resistance (but not to rilpivirine or doravirine) will maintain their virologic suppression after a drug regimen switch from rilpivirine/emtricitabine/tenofovir alafenamide in combination with dolutegravir, to bictegravir/emtricitabine/tenofovir alafenamide in combination with doravirine. The switch therapy will avoid food interactions, and will be well tolerated by subjects.

Study Overview

• Status: Completed
• Conditions: HIV-1-infection
• Intervention / Treatment: Drug: Bictegravir/emtricitabine/tenofovir alafenamide + Doravirine switch

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94114
      • SFOMG Private Practice

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• HIV positive Males, age 45 or older
• Any genotypic or phenotypic resistance except k65R, 69 insertion, integrase resistance, or resistance to rilpivarine or doravirine.
• Receiving combination antiretroviral regimen of rilpivirine/emtricitabine/tenofovir alafenamide in combination with dolutegravir > 12 months and with viral load <50 copies/ mL on at least one occasion within the six months prior to switch.
• Suppressed viral load as defined by one plasma HIV RNA level < 50 copies/mL within previous 6 months.
• Capable of providing informed consent

Exclusion Criteria:

• Any current or prior integrase inhibitor resistance
• Nucleoside reverse transcriptase (NRTI) mutation 69 insertion or k65R mutation
• Documented second generation non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance (rilpivirine or doravirine)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Biktarvy + Doravirine Switch; bictegravir 50mg/emtricitabine 200mg/tenofovir alafenamide 25mg tablets + doravirine 100mg tablets taken orally once per day

Drug: Bictegravir/emtricitabine/tenofovir alafenamide + Doravirine switch; Safety and efficacy of switching from rilpivirine/emtricitabine/tenofovir alafenamide in combination with dolutegravir, to bictegravir/emtricitabine/tenofovir alafenamide in combination with doravirine in male, 45+ year old subjects. The study will also include secondary outcomes of quality of life (QOL) and weight changes.; Other Names: Biktarvy + Pifeltro Switch

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Viral Suppression	Percentage of patients with viral HIV load (VL) <50 and <200 copies/mL at 48 weeks	48 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Body Mass Index	Assess changes in BMI due to treatment switch	Week 48
PK Assessment	Subject plasma concentration-time data of bictegravir and doravirine will be analyzed using non-compartmental model (WinNonlin®)	Week 4 (+/- 14 days) with time points at predose (-0.5 hr), 0.5, 1, 2, 4, 6, 8, 12, and 24 hours
Adverse Events Assessment	Assess AE's of any grade and relationship to the drug combination occurring in at least 5% of participants or more.	Day 28, Weeks 12, 24, 36, & 48
Wellbeing Improvement	Improvement in well-being and sleep inventory as measured by The Pittsburgh Sleep Quality Index (PSQI). Minimum score is 0 and maximum score is 21. A higher score indicates worse quality sleep.	Week 48
Tolerability of Study Drug	Tolerability of study drugs will be assessed by summarizing the number of AE/SAEs occurring during the study	Week 48
Work Productivity and Activity	Improvement in work productivity and activity as measured by Work Productivity and Activity Impairment Questionnaire (WPAI). The range of the scale is 0-10, where 0 means it did not have an affect and 10 means it did have an affect.	Week 48

Collaborators and Investigators

• Sponsor: Quest Clinical Research
• Collaborators: Gilead Sciences

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2019
• Primary Completion (Actual): November 11, 2021
• Study Completion (Actual): November 11, 2021

Study Registration Dates

• First Submitted: August 26, 2020
• First Submitted That Met QC Criteria: September 2, 2020
• First Posted (Actual): September 3, 2020

Study Record Updates

• Last Update Posted (Actual): March 5, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: multi-drug resistant
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir; Emtricitabine; Emtricitabine tenofovir alafenamide
• Other Study ID Numbers: BETD-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No