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

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ClinicalTrials.gov Identifier: NCT02401828
Recruitment Status : Unknown
Verified February 2017 by Bart Rijnders, Erasmus Medical Center.
Recruitment status was:  Active, not recruiting
First Posted : March 30, 2015
Last Update Posted : February 7, 2017
Sponsor:
Information provided by (Responsible Party):
Bart Rijnders, Erasmus Medical Center

Tracking Information
First Submitted Date  ICMJE March 19, 2015
First Posted Date  ICMJE March 30, 2015
Last Update Posted Date February 7, 2017
Study Start Date  ICMJE March 2015
Estimated Primary Completion Date June 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 26, 2015)
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
Original Primary Outcome Measures  ICMJE
 (submitted: March 24, 2015)
Efficacy of dolutegravir monotherapy in maintaining virological suppression [ Time Frame: 24 weeks ]
HIV-RNA <200c/ml at week 24 after baseline
Change History Complete list of historical versions of study NCT02401828 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 26, 2015)
  • 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
  • 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
  • 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
  • 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
  • Evaluate the evolution of CD4 associated HIV-1 reservoir [ Time Frame: 48 weeks ]
    Total/integrated HIV-DNA & 2LTR
  • Evaluate the number and type of INI resistance mutation in patients with virological failure [ Time Frame: 48 weeks ]
    Virological failure: HIV-RNA >200c/ml
  • Evaluate CD4 cell count change [ Time Frame: 48 weeks ]
    Compare baseline vs. 48 weeks after baseline
  • Evaluate changes in renal function after 24 and 48 weeks of dolutegravir monotherapy [ Time Frame: 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
  • Evaluate change in BMD after 24 and 48 weeks of dolutegravir mono-therapy [ Time Frame: 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 ]
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: March 24, 2015)
  • Time to loss of virological response (TLOVR) [ Time Frame: 1 week ]
    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 [ Time Frame: 24 weeks ]
    HIV-RNA <200c/ml at week 24 after baseline
  • Efficacy of dolutegravir monotherapy in maintaining virological suppression [ Time Frame: 48 weeks ]
    HIV-RNA <50 & <200 at week 24 & 48
  • 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
  • Evaluate the evolution of CD4 associated HIV-1 reservoir [ Time Frame: 48 weeks ]
    Total/integrated HIV-DNA & 2LTR
  • Evaluate the number and type of INI resistance mutation in patients with virological failure [ Time Frame: 48 weeks ]
    Virological failure: HIV-RNA >200c/ml
  • Evaluate CD4 cell count change [ Time Frame: 48 weeks ]
    Compare baseline vs. 48 weeks after baseline
  • Evaluate changes in renal function after 24 and 48 weeks of dolutegravir monotherapy [ Time Frame: 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
  • Evaluate change in BMD after 24 and 48 weeks of dolutegravir mono-therapy [ Time Frame: 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Dolutegravir Antiretroviral Mono-Therapy for HIV Trial
Official Title  ICMJE The Dolutegravir Antiretroviral Mono-Therapy for HIV Trial
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Human Immunodeficiency Virus
Intervention  ICMJE Drug: Dolutegravir
Switch from combination antiretroviral therapy to dolutegravir monotherapy
Other Names:
  • Tivicay
  • S/GSK1349572
Study Arms  ICMJE
  • 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
    Intervention: Drug: Dolutegravir
  • 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
    Intervention: Drug: Dolutegravir
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Actual Enrollment  ICMJE
 (submitted: October 26, 2015)
134
Original Estimated Enrollment  ICMJE
 (submitted: March 24, 2015)
104
Estimated Study Completion Date  ICMJE July 2017
Estimated Primary Completion Date June 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02401828
Other Study ID Numbers  ICMJE NL51858.078.14
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Bart Rijnders, Erasmus Medical Center
Study Sponsor  ICMJE Erasmus Medical Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Bart Rijnders, MD, PhD Erasmus MC
PRS Account Erasmus Medical Center
Verification Date February 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP