B-free Multistage Trial

NCT06037564 | Enrolling By Invitation Phase 4 DMC

• 1 other identifier: B-free trial - Stage 1
• Study Type: interventional
• Target: 210
• Locations: 1 country
• Sites: 8

Brief Summary

The primary objective of the study is to evaluate the efficacy of a booster-free regimen including DOR/DTG/3TC among HIV-suppressed PLWH with previous virological failure. The key secondary objectives are i) to determine whether switching to DOR / DTG / 3TC leads to lower burden of DDI compared to continuing a booster-containing regimen, and ii) to assess changes in patient perception on treatment acceptability and satisfaction, as well as health-related quality of life after a switch to booster-free ART. Qualitative sub-study: Qualitative objectives will be met using semi-structured interviews. Thirty people (15 from the intervention arm, 15 from the control arm) will be interviewed twice, at week 0 and week 48. Additional 15 individuals from the observational cohort will be interviewed once. Interviews will take place following study visits and performed using semi-structured guides. The guide for the interviews at week 48 will be based on results from analyses of the interviews conducted at week 0.

Conditions

HIV; Drug Resistance; Drug Drug Interaction

Keywords

HIV; Doravirine; Dolutegravir; Drug resistance; Drug-drug interaction

Outcome Measures

Primary Outcomes (1)

• Loss of viral suppression

  Difference in the proportion of individuals with an HIV-RNA ≥50 cp/mL at 48 weeks between the treatment arms.

  Week 48

Secondary Outcomes (17)

• Changes in DDI score from week 0 to 48

  Week 0 and 48

• Patient report outcomes concerning changes in treatment satisfaction between baseline and 48 weeks, as determined using the HIV Treatment Satisfaction Questionnaire HIVTSQc (change version).

  Week 0 to 48

• Proportion of patients experiencing confirmed virological failure

  Week 48

• Proportion of individuals detected with new drug resistance

  Week 0 to 48

• Proportion of individuals with any moderate (orange flag) or severe (red flag) DDI

  Week 0 to 48

Other Outcomes (12)

• Change in CD4 cell count from baseline to week 48

  Week 0 and 48

• Change in metabolic variables (cholesterol)

  Week 0 and 48

• Change in metabolic variables (low density lipoprotein)

  Week 0 and 48

Study Arms (2)

Intervention

EXPERIMENTAL

Doravirine 100 mg (Pifeltro®) will be administered once daily in combination with co-formulated dolutegravir/lamivudine 50/300 mg (Dovato®) for a duration of 48 weeks.

Drug: DOR/DTG/3TC

Control

NO INTERVENTION

Participants randomized to the control arm will continue to take their fully suppressive ART at baseline. The following selection of treatment combinations could be encountered in the control group (among others): * Once-daily co-formulated elvitegravir 150 mg, cobicistat 150 mg, tenofovir alafenamide 10 mg, emtricitabine 200 mg (Genvoya®) and darunavir 800 mg (e.g. Darunavir Mylan®) * Once-daily co-formulated darunavir 800 mg, cobicistat 150 mg, tenofovir alafenamide 10 mg, emtricitabine 200 mg (Symtuza ®) and DTG 50 mg (Tivicay ®) * Once-daily DTG 50 mg (Tivicay®), darunavir 800 mg (e.g. Darunavir Mylan®), and ritonavir 100 mg (Norvir®) * Etravirine 200 mg twice daily (Intelence®), raltegravir 400 mg twice daily (Isentress®),darunavir 800 mg once daily (e.g. Darunvair Mylan®) and ritonavir 100 mg once daily (Norvir®)

Interventions

DOR/DTG/3TC DRUG

Doravirine 100 mg (Pifeltro®) will be administered once daily in combination with co-formulated dolutegravir/lamivudine 50/300 mg (Dovato®) for a duration of 48 weeks.

Also known as: Doravirine (Pifeltro®) + Dolutegravir/Lamivudine (Dovato®)

Intervention

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent as documented by signature
• Age ≥18 years
• Documented HIV-1 infection
• On ART including a pharmacological booster (ritonavir or cobicistat) and at least 2 drugs from classes other than NRTI (e.g. non-nucleoside reverse transcriptase inhibitor, integrase-inhibitor, protease inhibitor or entry inhibitor)
• History of ART change due to virological failure
• HIV-RNA \<50 cp/mL at screening and for at least 24 weeks before screening, one blip with less than 200 cp/mL allowed

You may not qualify if:

• Creatinine clearance \<30mL/min, calculated using the CKD-EPI formula
• Known hypersensitivity, allergy, or intolerance to DOR, DTG, or 3TC
• Presence of major drug resistance mutations against DTG (G118R, G140R, Q148H, Q148K, Q148R, R263K) or DOR (V106A, Y188L, F227C, F227L, M230L, Y318F) according to IAS-USA in individual cumulative resistance analyses. Patients without available resistance testing should not be excluded if no resistance to DTG and/or DOR is assumed based on ART history.
• Concomitant use of drugs that decrease DTG or DOR blood concentrations
• Chronic hepatitis B infection, defined as a positive hepatitis B surface antigen (HBsAg) at the screening visit
• Women who are pregnant or breast-feeding. Women of childbearing potential (women who are not surgically sterilized / hysterectomised and / or post-menopausal for longer than 2 years must have a negative pregnancy test at screening).
• Participation in another ART intervention study within the 30 days preceding and during the present study.
• Qualitative sub-study

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead
• Center for Primary Care and Public Health (Unisante), University of Lausanne, Switzerland: collaborator
• University of Bern: collaborator

Study Sites (8)

Cantonal Hospital Aarau

Aarau, Canton of Aargau, 5001, Switzerland

Location

University Hospital Basel

Basel, Switzerland

Location

Inselgruppe AG

Bern, 3010, Switzerland

Location

University Hospital Geneva

Geneva, Switzerland

Location

University of Lausanne Hospitals

Lausanne, Switzerland

Location

Lugano Regional Hospital Lugano

Lugano, Switzerland

Location

Cantonal Hospital of St. Gallen

Sankt Gallen, Switzerland

Location

University Hospital Zürich

Zurich, Switzerland

Location

Related Publications (1)

• Ballif M, Braun D, Calmy A, Bernasconi E, Cavassini M, Tissot F, Stoeckle M, Schmid P, Fux CA, Van der Valk M, Brinkman K, Mudrikova T, Bonnet F, Leleux O, Saude M, Hirter D, Schwab N, Limacher A, Rintelen F, Kouyos R, Haerry D, Zambrano SC, Egloff M, Akre C, Peytremann-Bridevaux I, Rauch A, Wandeler G, Surial B. Booster-free anti-retroviral therapy for persons living with HIV and multidrug resistance (B-Free): protocol for a multicentre, multistage, randomised, controlled, non-inferiority trial. BMJ Open. 2024 Nov 21;14(11):e094912. doi: 10.1136/bmjopen-2024-094912.

  PMID: 39578038 DERIVED

MeSH Terms

Interventions

doravirine; dolutegravir; Lamivudine

Intervention Hierarchy (Ancestors)

Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides

Study Officials

• Gilles Wandeler, Prof

  Inselspital, Bern, Switzerland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multi-stage, randomized, multicenter, open-label non-inferiority trial with active control

Study Record Dates

• First Submitted: April 24, 2023
• First Posted: September 14, 2023
• Study Start: November 13, 2023
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): September 1, 2027
• Last Updated: December 4, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CH (8)