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

• ClinicalTrials.gov Identifier: NCT02401828
• Recruitment Status: Completed
• First Posted: March 30, 2015
• Last Update Posted: January 28, 2020
• Sponsor: Erasmus Medical Center
• Information provided by (Responsible Party): Bart Rijnders, Erasmus Medical Center

Tracking Information

• First Submitted Date: March 19, 2015
• First Posted Date: March 30, 2015
• Last Update Posted Date: January 28, 2020
• Actual Study Start Date: March 2015
• Actual Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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

Current Secondary Outcome Measures (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 (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: The Dolutegravir Antiretroviral Mono-Therapy for HIV Trial
• Official Title: 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: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Human Immunodeficiency Virus

Intervention

Drug: Dolutegravir

Switch from combination antiretroviral therapy to dolutegravir monotherapy

Other Names:

• Tivicay
• S/GSK1349572

Study Arms

• 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 *

• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 26, 2015): 134
• Original Estimated Enrollment (submitted: March 24, 2015): 104
• Actual Study Completion Date: July 2017
• Actual Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)

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:

  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

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Netherlands

Administrative Information

• NCT Number: NCT02401828
• Other Study ID Numbers: NL51858.078.14
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Bart Rijnders, Erasmus Medical Center
• Original Responsible Party: Same as current
• Current Study Sponsor: Erasmus Medical Center
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Erasmus Medical Center
• Verification Date: January 2020