Dual Therapy With Boosted Darunavir + Dolutegravir (Dualis)

November 23, 2023 updated by: Technical University of Munich

A Prosp., Multic., Randomized, Open-label Trial to Assess the Safety, Tolerability and Efficacy of Dual Therapy With Boosted Darunavir + Dolutegravir When Switching From SOC ART in HIV-patients With Sustained Virological Suppr.

A switch strategy to investigate whether a dual therapy with Ritonavir-boosted (RTV) Darunavir (DRV) + Dolutegravir (DTG) over 48 weeks is non-inferior to a continuous standard of care therapy with RTV-boosted DRV in combination with 2 Nucleosidic Reverse Transcriptase Inhibitors (NRTIs) in HIV patients, who are on a stable antiretroviral therapy (ART) with RTV-boosted DRV in combination with 2 NRTIs.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Modern combination antiretroviral therapy (cART) leads to well-controlled HIV infection with a potentially normal life expectancy. Nucleosidic reverse transcriptase inhibitors (NRTIs) play a major role as "ART backbone" and are essential antiretroviral agents according to current European and WHO HIV treatment guidelines. However, NRTI use can be associated with substantial side effects, e.g. bone and kidney toxicity, lipotoxicity and mitochondrial toxicity and can put patients at serious risk. Especially long-term NRTI-exposure is a risk factor for these often cumulative side effects, since the standard of care (SOC) therapy with the different NRTIs consists of the combination of multiple substances. Furthermore NRTI resistances may emerge over time and limit treatment options for pre-treated HIV patients.

As a consequence, alternative NRTI free (so called "nuke sparing") therapy options have been evaluated in different studies but were associated with less virologic therapeutic success and higher rates of therapy induced resistance compared to standard regimens in ART naïve patients. This is particularly true for patients with a high baseline viral load.

As an alternative to NRTI-based therapy options, Ritonavir-boosted protease inhibitor (PI/r)-based nuke-sparing dual therapies have been studied widely, mostly in combination with the integrase inhibitor (INI) Raltegravir (RAL). In this setting, the PI was not fully capable to prevent the development of INI resistant viruses.

The HIV protease inhibitor Darunavir (DRV) and the novel INI Dolutegravir (DTG) are both very potent anchor drugs with a high barrier to resistance. Due to a favourable side-effect profile, a once-daily (QD) formulation and its virological potency, DRV is currently one of the most frequently used PIs in Europe and the USA. In addition, the new, once-daily administrable integrase inhibitor DTG showed an excellent tolerability profile as well as a high resistance barrier.

The nuke-free combination of DTG (50 mg) with the Ritonavir (/r)- or Cobicistat-boosted protease inhibitor DRV (800 mg) may offer a favorable safety and efficacy profile with the advantage of QD-dosing.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
269

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Munich, Germany, 81675
        • Klinikum Rechts der Isar

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age ≥ 18 years
  • HIV infection with HIV RNA < 50 cps/ml within a period of at least 24 weeks suppressive ART prior to randomization, with one accepted blip of HIV RNA < 200 cps/ml and well-tolerated antiretroviral therapy: consisting of 2 NRTI (ABC/3TC, F/TDF or F/TAF) in combination with DRV/r for a period of at least 28 days prior to randomizsation.
  • No known genotypic DRV- or integrase inhibitor-related HIV resistance
  • Signed written informed consent
  • Documented negative HLA B*57:01 (only in case of Abacavir-containing ART)

  • A female subject may be eligible to enter and participate in the study if she:

    • is of non-child-bearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and ≥ 45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy or
    • is of child-bearing potential with a negative pregnancy test at both screening and Day 1 and agrees to use one of the following methods of contraception to avoid pregnancy:
  • Complete abstinence from penile-vaginal intercourse from 2 weeks prior to administration of IMP, throughout the study, and for at least 2 weeks after discontinuation of all study medications
  • Double barrier method (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide)
  • Male partner sterilization confirmed prior to the female subject's entry into the study, and this male is the sole partner for that subject
  • Approved hormonal contraception without DRV/r interactions and a barrier method
  • Any other method with published data showing that the expected failure rate is <1% per year. Any contraception method must be used consistently, in accordance with the approved product label and for at least 2 weeks after discontinuation of IMP.

Exclusion Criteria:

  • Pregnant women and nursing mothers
  • Chronic HBV infection (HBsAg positive); known anti-HBsAb > 10 IU/ml within the last 36 months or a history of infection with known anti-HBcAb positive AND anti-HBsAb > 10 IU/ml AND HBsAg-loss are not exclusionary)
  • Any evidence of a Center for Disease Control and Prevention (CDC) Category C disease at screening, except cutaneous Kaposi's sarcoma not requiring systemic therapy. Historical or current CD4 cell counts < 200 cells/mm3 or historic CDC C diseases are not exclusionary
  • History or presence of allergy to the study drugs or their components
  • Subject has creatinine clearance of <50 mL/min by MDRD eGFR calculation
  • Alanine aminotransferase (ALT) ≥ 5 times the upper limit of normal (ULN), OR ALT ≥ 3xULN and bilirubin ≥ 1.5xULN (with >35% direct bilirubin)
  • Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
  • Subjects with severe hepatic impairment (Class B or greater) as determined by Child-Pugh classification
  • Anticipated need for interferon-based Hepatitis C virus (HCV) therapy during the study
  • Participation in other interventional clinical trials at the same time
  • Persons with any kind of dependency on the investigator or employed by the sponsor or investigator
  • Persons held in an institution by legal or official order
  • Imprisoned people, people requiring in-house treatment for psychiatric disorders or people who are unable to give informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: A: boosted darunavir (bDRV) plus dolutegravir (DTG; 2DR)
Prezista & Norvir & Tivicay
Drug: Prezista
once daily
Other Names:
  • Darunavir
Drug: Norvir
once daily
Other Names:
  • Ritonavir
Drug: Tivicay
once daily
Other Names:
  • Dolutegravir
Active Comparator: B: bDRV plus 2 nucleoside reverse-transcriptase inhibitors (NRTIs; 3DR)
Prezista & Norvir & Truvada or Prezista & Norvir & Kivexa or Prezista & Norvir & Descovy
Drug: Prezista
once daily
Other Names:
  • Darunavir
Drug: Norvir
once daily
Other Names:
  • Ritonavir
Drug: Truvada
once daily
Other Names:
  • Tenofovir disaproxil fumarat/emtricitabine
Drug: Kivexa
once daily
Other Names:
  • Abacavir/Lamivudine
Drug: Descovy
once daily
Other Names:
  • Tenofovir alafenamid / emtricitabine

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
number (%) of patients with fully suppressed HIV RNA < 50 cps/ml at week 48
Time Frame: 48 weeks
For primary endpoint, HIV RNA suppression < 50 cps/ml will be assessed at week 48, using NAT diagnostic.
48 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Technical University of Munich

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Christoph Spinner, MD, Dep. of Medicine II & IZAR, Klinikum rechts der Isar der TUM

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 31, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 31, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 15, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 26, 2015

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 1, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 29, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 23, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • DUA-1463-SPI-0320-I

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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