The Dolutegravir Antiretroviral Mono-Therapy for HIV Trial (DOMONO)

January 27, 2020 updated by: Bart Rijnders, Erasmus Medical Center

48-week open label randomized phase IV investigator initiated intervention study. The purpose of this study is to evaluate whether HIV-1 suppression can be maintained by DTG monotherapy in HIV-1 infected, virologically suppressed patients on cART.

104 adults fulfilling the in and exclusion criteria and on stable cART will be randomized over 2 investigational arms.

The first arm will contain the direct switch population. This population will switch directly from stable cART to Dolutegravir mono-therapy on baseline visit.

The second arm will contain the delayed-switch population. This group will switch from stable cART to Dolutegravir monotherapy 24 weeks after baseline visit.

The main goal is to investigate if Dolutegravir mono-therapy could be non-inferior to cART in virological suppressed HIV-1 infected adults.

If a interim analysis (performed when 40 patients on dolutegravir monotherapy have passed week 12) shows that it is safe to continue the study, an additional 30 patients will be included on top of the 104 patients needed for the primary endpoint analysis. In contrast to the primary endpoint population, these additional 30 patients will have a CD4 nadir <200 but a CD4 >350 at the time of the screening visit. Besides that, these 30 patients will have to fulfill all other in and exclusion criteria of the primary endpoint population (specifically a viral load never >100.000). These 30 patients are part of a pilot study looking at the possibility to broaden the eligible population in a future larger randomized clinical trial.

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

DTG Monotherapy will be considered non-inferior to cART if the lower bound of the one sided 97.5%CI for the difference in proportion of patients reaching the primary endpoint is not lower than -12%. For this purpose, a sample size of 52 per arm would provide 80% power at alpha 0.025 to establish non-inferiority of DTG monotherapy compared with cART when the primary endpoint success rate is 95% in both treatment arms.

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.
134

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 4

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

  • Netherlands
    • Zuid Holland
      • Rotterdam, Zuid Holland, Netherlands, 3000 CA
        • Erasmus Medical Center

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Documented HIV-1 positive by ELISA or Western Blot or Plasma HIV-RNA >1000 c/ml.
  • 18 years or older.
  • HIV-RNA ≤50 copies/mL for ≥24 weeks.
  • Historical baseline HIV-RNA plasma load <100.000 c/ml
  • CD4 count nadir pre-cART ≥200 cells/mm3
  • Not on strong UGT1A1 or CYP3A4 inducing agents as stated in DTG SPC.
  • General medical condition does not interfere with trial procedures (on investigators' discretion)
  • Females should have no plans of becoming pregnant during the next 18 months after the baseline visit

  • Females are eligible if:

    1. They do not plan to become pregnant during the study
    2. Negative screening pregnancy test and uses one of the following methods: 1.Abstinence from penile/vaginal intercourse during the study; 2.Double barrier contraceptive methods 1 of which must be condom.

Exclusion Criteria:

  • Previous virological failure on any ART.
  • Patient without documented anti-HBs antibodies.
  • Subjects positive for hepatitis B at screening (HBsAg+).
  • Any documented genotypic HIV-1 resistance with at least low-level resistance according to stanford HIV drug resistance database
  • No record of the historical baseline plasma viral load available
  • Subjects with concomitant CDC-C opportunistic infections within 90 days of screening.
  • Subjects with history of allergy to INI.
  • Subjects with creatinine clearance <50mL/min according to CKD-EPI.
  • Subjects with hepatic impairment of at least Child-Pugh B.
  • Exposure to experimental drug or experimental HIV-1 vaccine within 90 days of start of DTG.
  • Screening ALT >5x ULN or ALT>3xULN and bilirubin >2 ULN.
  • Patient (man or woman) planning or hoping to conceive a child/become pregnant during the study
  • Patients who cannot take DTG 2 hours before or 6 hours after antacids, calciumcarbonate or iron supplements.

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: Group A - Direct Switch
Direct switch from cART to Dolutegravir mono-therapy at baseline. Dolutegravir single tablet 50mg QD, once a day. Duration = 48 weeks
Drug: Dolutegravir
Switch from combination antiretroviral therapy to dolutegravir monotherapy
Other Names:
  • Tivicay
  • S/GSK1349572
Experimental: Group B - Delayed Switch
Delayed switch from cART to Dolutegravir mono-therapy at week 24 from baseline. Dolutegravir single tablet 50mg QD, once a day. Duration = 48 weeks
Drug: Dolutegravir
Switch from combination antiretroviral therapy to dolutegravir monotherapy
Other Names:
  • Tivicay
  • S/GSK1349572

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
Efficacy of dolutegravir monotherapy in maintaining virological suppression in the on-treatment population
Time Frame: 24 weeks
HIV-RNA <200c/ml at week 24 after baseline
24 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Time to loss of virological response (TLOVR) in the OT population
Time Frame: 1 week
Time to first of two confirmed HIV-RNA >50c/ml at least 1 week apart
1 week
Efficacy of dolutegravir monotherapy in maintaining virological suppression in the entire study population (ITT)
Time Frame: 24 weeks
HIV-RNA <200c/ml at week 24 after baseline
24 weeks
Efficacy of dolutegravir monotherapy in maintaining virological suppression in the on-treatment population
Time Frame: 48 weeks
HIV-RNA <50 & <200 at week 24 & 48
48 weeks
Evaluate safety of Dolutegravir monotherapy (Acquired resistance & Adverse Events according to CDC 4.0)
Time Frame: 60 weeks
Acquired resistance & Adverse Events according to CDC 4.0
60 weeks
Evaluate the evolution of CD4 associated HIV-1 reservoir
Time Frame: 48 weeks
Total/integrated HIV-DNA & 2LTR
48 weeks
Evaluate the number and type of INI resistance mutation in patients with virological failure
Time Frame: 48 weeks
Virological failure: HIV-RNA >200c/ml
48 weeks
Evaluate CD4 cell count change
Time Frame: 48 weeks
Compare baseline vs. 48 weeks after baseline
48 weeks
Evaluate changes in renal function after 24 and 48 weeks of dolutegravir monotherapy
Time Frame: 48 weeks
48 weeks
Cost effectiveness of DTG monotherapy
Time Frame: 48 weeks
Cost per QALY during DTG monotherapy in comparison with the costs of therapy with the patient's own cART regimen used before study inclusion
48 weeks
Evaluate change in BMD after 24 and 48 weeks of dolutegravir mono-therapy
Time Frame: 48 weeks
48 weeks
Exploratory analysis of blood pressure, weight, BMI, fasting serum lipids, Framingham risk score, ATP-III treatment goals and inflammatory markers after 24wks of dolutegravir mono-therapy
Time Frame: 48 weeks
48 weeks
Efficacy of dolutegravir monotherapy in maintaining virological suppression in the on-treatment population
Time Frame: 12 weeks
HIV-RNA <200c/ml and <50 at week 12 after baseline
12 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.
Erasmus Medical Center

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.
  • Principal Investigator: Bart Rijnders, MD, PhD, Erasmus Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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.
March 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.
June 1, 2017

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.
July 1, 2017

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).
March 19, 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.
March 24, 2015

First Posted (Estimate)

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.
March 30, 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.
January 28, 2020

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.
January 27, 2020

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.
January 1, 2020

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.
  • NL51858.078.14

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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