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

Primary Purpose

Human Immunodeficiency Virus

Status
Completed
Phase
Phase 4
Locations
Netherlands
Study Type
Interventional
Intervention
Dolutegravir
Sponsored by
Erasmus Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Human Immunodeficiency Virus

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Erasmus Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Group A - Direct Switch

Group B - Delayed Switch

Arm Description

Direct switch from cART to Dolutegravir mono-therapy at baseline. Dolutegravir single tablet 50mg QD, once a day. Duration = 48 weeks

Delayed switch from cART to Dolutegravir mono-therapy at week 24 from baseline. Dolutegravir single tablet 50mg QD, once a day. Duration = 48 weeks

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Time to loss of virological response (TLOVR) in the OT population
Time to first of two confirmed HIV-RNA >50c/ml at least 1 week apart
Efficacy of dolutegravir monotherapy in maintaining virological suppression in the entire study population (ITT)
HIV-RNA <200c/ml at week 24 after baseline
Efficacy of dolutegravir monotherapy in maintaining virological suppression in the on-treatment population
HIV-RNA <50 & <200 at week 24 & 48
Evaluate safety of Dolutegravir monotherapy (Acquired resistance & Adverse Events according to CDC 4.0)
Acquired resistance & Adverse Events according to CDC 4.0
Evaluate the evolution of CD4 associated HIV-1 reservoir
Total/integrated HIV-DNA & 2LTR
Evaluate the number and type of INI resistance mutation in patients with virological failure
Virological failure: HIV-RNA >200c/ml
Evaluate CD4 cell count change
Compare baseline vs. 48 weeks after baseline
Evaluate changes in renal function after 24 and 48 weeks of dolutegravir monotherapy
Cost effectiveness of DTG monotherapy
Cost per QALY during DTG monotherapy in comparison with the costs of therapy with the patient's own cART regimen used before study inclusion
Evaluate change in BMD after 24 and 48 weeks of dolutegravir mono-therapy
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
Efficacy of dolutegravir monotherapy in maintaining virological suppression in the on-treatment population
HIV-RNA <200c/ml and <50 at week 12 after baseline

Full Information

First Posted
March 19, 2015
Last Updated
January 27, 2020
Sponsor
Erasmus Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT02401828
Brief Title
The Dolutegravir Antiretroviral Mono-Therapy for HIV Trial
Acronym
DOMONO
Official Title
The Dolutegravir Antiretroviral Mono-Therapy for HIV Trial
Study Type
Interventional

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
March 2015 (Actual)
Primary Completion Date
June 2017 (Actual)
Study Completion Date
July 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Erasmus Medical Center

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Human Immunodeficiency Virus

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
134 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group A - Direct Switch
Arm Type
Experimental
Arm Description
Direct switch from cART to Dolutegravir mono-therapy at baseline. Dolutegravir single tablet 50mg QD, once a day. Duration = 48 weeks
Arm Title
Group B - Delayed Switch
Arm Type
Experimental
Arm Description
Delayed switch from cART to Dolutegravir mono-therapy at week 24 from baseline. Dolutegravir single tablet 50mg QD, once a day. Duration = 48 weeks
Intervention Type
Drug
Intervention Name(s)
Dolutegravir
Other Intervention Name(s)
Tivicay, S/GSK1349572
Intervention Description
Switch from combination antiretroviral therapy to dolutegravir monotherapy
Primary Outcome Measure Information:
Title
Efficacy of dolutegravir monotherapy in maintaining virological suppression in the on-treatment population
Description
HIV-RNA <200c/ml at week 24 after baseline
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Time to loss of virological response (TLOVR) in the OT population
Description
Time to first of two confirmed HIV-RNA >50c/ml at least 1 week apart
Time Frame
1 week
Title
Efficacy of dolutegravir monotherapy in maintaining virological suppression in the entire study population (ITT)
Description
HIV-RNA <200c/ml at week 24 after baseline
Time Frame
24 weeks
Title
Efficacy of dolutegravir monotherapy in maintaining virological suppression in the on-treatment population
Description
HIV-RNA <50 & <200 at week 24 & 48
Time Frame
48 weeks
Title
Evaluate safety of Dolutegravir monotherapy (Acquired resistance & Adverse Events according to CDC 4.0)
Description
Acquired resistance & Adverse Events according to CDC 4.0
Time Frame
60 weeks
Title
Evaluate the evolution of CD4 associated HIV-1 reservoir
Description
Total/integrated HIV-DNA & 2LTR
Time Frame
48 weeks
Title
Evaluate the number and type of INI resistance mutation in patients with virological failure
Description
Virological failure: HIV-RNA >200c/ml
Time Frame
48 weeks
Title
Evaluate CD4 cell count change
Description
Compare baseline vs. 48 weeks after baseline
Time Frame
48 weeks
Title
Evaluate changes in renal function after 24 and 48 weeks of dolutegravir monotherapy
Time Frame
48 weeks
Title
Cost effectiveness of DTG monotherapy
Description
Cost per QALY during DTG monotherapy in comparison with the costs of therapy with the patient's own cART regimen used before study inclusion
Time Frame
48 weeks
Title
Evaluate change in BMD after 24 and 48 weeks of dolutegravir mono-therapy
Time Frame
48 weeks
Title
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
Title
Efficacy of dolutegravir monotherapy in maintaining virological suppression in the on-treatment population
Description
HIV-RNA <200c/ml and <50 at week 12 after baseline
Time Frame
12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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: They do not plan to become pregnant during the study 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bart Rijnders, MD, PhD
Organizational Affiliation
Erasmus Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Erasmus Medical Center
City
Rotterdam
State/Province
Zuid Holland
ZIP/Postal Code
3000 CA
Country
Netherlands

12. IPD Sharing Statement

Citations:
PubMed Identifier
29617822
Citation
Wijting IEA, Lungu C, Rijnders BJA, van der Ende ME, Pham HT, Mesplede T, Pas SD, Voermans JJC, Schuurman R, van de Vijver DAMC, Boers PHM, Gruters RA, Boucher CAB, van Kampen JJA. HIV-1 Resistance Dynamics in Patients With Virologic Failure to Dolutegravir Maintenance Monotherapy. J Infect Dis. 2018 Jul 24;218(5):688-697. doi: 10.1093/infdis/jiy176.
Results Reference
derived
PubMed Identifier
29107562
Citation
Wijting I, Rokx C, Boucher C, van Kampen J, Pas S, de Vries-Sluijs T, Schurink C, Bax H, Derksen M, Andrinopoulou ER, van der Ende M, van Gorp E, Nouwen J, Verbon A, Bierman W, Rijnders B. Dolutegravir as maintenance monotherapy for HIV (DOMONO): a phase 2, randomised non-inferiority trial. Lancet HIV. 2017 Dec;4(12):e547-e554. doi: 10.1016/S2352-3018(17)30152-2. Epub 2017 Oct 26.
Results Reference
derived

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The Dolutegravir Antiretroviral Mono-Therapy for HIV Trial

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