B-free Multistage Trial

NCT ID: NCT06037564

Last Updated: 2024-12-04

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Clinical Phase: PHASE4
• Total Enrollment: 210 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-11-13
• Study Completion Date: 2027-09-30

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.

Detailed Description

Life expectancy of persons living with HIV on antiretroviral therapy (ART) is increasing and drug-drug interactions (DDI) with co-medications are becoming a major concern. Individuals who previously experienced virological failure are at risk of DDI as they are generally treated with ritonavir- or cobicistat-boosted ART. The high potency as well as the favorable safety and pharmacokinetic profile of new antiretroviral drugs, including dolutegravir (DTG) and doravirine (DOR), support their evaluation as part of un-boosted therapy for individuals with a history of virological failure. In this adaptive trial within the Swiss HIV Cohort Study (SHCS) and partner clinics in the Netherlands, the investigators aim to evaluate the efficacy and acceptability of the booster-free regimen DOR/DTG/3TC for treatment-experienced individuals.

Conditions

HIV; Drug Resistance; Drug Drug Interaction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Intervention

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.

Group Type: EXPERIMENTAL

DOR/DTG/3TC

Intervention Type: 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.

Control

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®)

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

DOR/DTG/3TC

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.

Intervention Type: DRUG

Other Intervention Names

Doravirine (Pifeltro®) + Dolutegravir/Lamivudine (Dovato®)

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Center for Primary Care and Public Health (Unisante), University of Lausanne, Switzerland

OTHER

Sponsor Role: collaborator

University of Bern

OTHER

Sponsor Role: collaborator

Insel Gruppe AG, University Hospital Bern

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilles Wandeler, Prof

Role: PRINCIPAL_INVESTIGATOR

Inselspital, Bern, Switzerland

Locations

Cantonal Hospital Aarau

Aarau, Canton of Aargau, Switzerland

University Hospital Basel

Basel, , Switzerland

Inselgruppe AG

Bern, , Switzerland

University Hospital Geneva

Geneva, , Switzerland

University of Lausanne Hospitals

Lausanne, , Switzerland

Lugano Regional Hospital Lugano

Lugano, , Switzerland

Cantonal Hospital of St. Gallen

Sankt Gallen, , Switzerland

University Hospital Zürich

Zurich, , Switzerland

Countries

Switzerland

References

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.

Reference Type: DERIVED

PMID: 39578038 (View on PubMed)

Other Identifiers

B-free trial - Stage 1

Identifier Type: -

Identifier Source: org_study_id