Back to resultsA Pilot Study of MONOtherapy of DOlutegravir in HIV-1 Virologically Suppressed Patients (MONODO)
Primary Purpose
Human Immunodeficiency Virus, Dolutegravir, Monotherapy
Status
Completed
Phase
Phase 2
Locations
Switzerland
Study Type
Interventional
Intervention
Dolutegravir
Sponsored by
About this trial
This is an interventional treatment trial for Human Immunodeficiency Virus focused on measuring Dolutegravir, HIV infection, Anti-Retroviral Agents, HIV Integrase Inhibitors, Integrase Inhibitors, Pharmacologic Actions, Therapeutic Uses
Eligibility Criteria
Inclusion Criteria:
- HIV-1 infection;
- Patient included in the Swiss HIV Cohort Study (SHCS);
- ≥ 18 years of age;
- Virologically suppressed for at least 24 months on first line triple ART (changes for toxicity permitted) with at least 4 HIV-1 RNA measurements in plasma <50 copies/ml;
- No history of previous failure on ART;
- No documented antiretroviral drugs resistance;
- No co-infection with Hepatitis B or C virus;
- Effective contraception in women;
- Willing to provide CSF and semen samples;
- Written informed consent
Exclusion Criteria:
- HIV-2 infection;
- Renal dysfunction (creatinine clearance <50ml/min);
- aspartate transaminase or alanine aminotransferase >5x upper limit normal;
- Concomitant use of carbamazepine, oxcarbazepine, phenytoin, phenobarbital, St John's wort, rifampicin or metformin;
- Previous AIDS defining conditions or active malignancy in the past five years;
- Positive HIV viral load in CSF at baseline;
- Known or suspected non-compliance;
- Women who are pregnant or breastfeeding.
Sites / Locations
- University Hospitals of Geneva, HIV unit
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Dolutegravir monotherapy
Arm Description
10 patients will be simplified to monotherapy of dolutegravir tablet 50mg once daily for 24 weeks
Outcomes
Primary Outcome Measures
Number of patients without virological failure defined as plasma HIV-1 RNA ≥ 200 copies/ml on two consecutive measurements or positive HIV-1 RNA level in cerebrospinal fluid (CSF) at week 24 or before
Secondary Outcome Measures
Quantification of the HIV-1 DNA reservoir in peripheral blood monocyte cells at baseline and week 24
Emergence of genotypic resistance in plasma HIV-1 RNA in case of virological failure
Quantification HIV-1 RNA levels in the CSF and semen at baseline and week 24
Lumbar puncture is optional at baseline
Change from baseline CD4 cell count from baseline at week 24
Adherence to medication at weeks 4, 8, 12, 16, 20, 24
Number of participants with suboptimal adherence defined as more than 3 pills (10%) remaining from previous monthly visit OR missed more than one dose in a row OR missed dose more than once every two weeks
Lipidic profile changes from baseline at week 24
Body fat composition as measured by dual energy x-ray absorptiometry (DXA) scan at baseline and week 24
Change in bone mineral density from baseline to week 24
Number of patients with normal bone density, osteopenia or osteoporosis as defined by DXA scans results
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02572947
Brief Title
A Pilot Study of MONOtherapy of DOlutegravir in HIV-1 Virologically Suppressed Patients
Acronym
MONODO
Official Title
An Interventional, One-arm, Open Label Pilot Study to Assess the Feasibility of Dolutegravir Monotherapy in Virologically Suppressed Patients on Conventional Triple Antiretroviral Therapy of Dolutegravir Plus Two Nucleoside Reverse Transcriptase Inhibitors
Study Type
Interventional
2. Study Status
Record Verification Date
October 2017
Overall Recruitment Status
Completed
Study Start Date
June 2016 (undefined)
Primary Completion Date
June 2017 (Actual)
Study Completion Date
September 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Calmy Alexandra
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Current HIV treatment guidelines recommend a combination of drugs for the maintenance of antiretroviral therapy (ART). Simplification is considered critical to further scale-up of treatment, to support retention in care and to reduce costs. Dolutegravir is a once daily integrase inhibitor that shows very good tolerability, efficacy, and distinctive resistance profile. The researchers aim at investigating the feasibility of dolutegravir monotherapy in maintenance therapy. Briefly, 10 virologically suppressed patients for at least six months on conventional triple ART of dolutegravir plus two nucleoside reverse transcriptase inhibitors (NRTIs) will be switched to dolutegravir monotherapy for 24 weeks. The primary endpoint is the number of patients completing 24 weeks of dolutegravir monotherapy without experiencing virological failure.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Human Immunodeficiency Virus, Dolutegravir, Monotherapy, Treatment Efficacy
Keywords
Dolutegravir, HIV infection, Anti-Retroviral Agents, HIV Integrase Inhibitors, Integrase Inhibitors, Pharmacologic Actions, Therapeutic Uses
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
8 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Dolutegravir monotherapy
Arm Type
Experimental
Arm Description
10 patients will be simplified to monotherapy of dolutegravir tablet 50mg once daily for 24 weeks
Intervention Type
Drug
Intervention Name(s)
Dolutegravir
Primary Outcome Measure Information:
Title
Number of patients without virological failure defined as plasma HIV-1 RNA ≥ 200 copies/ml on two consecutive measurements or positive HIV-1 RNA level in cerebrospinal fluid (CSF) at week 24 or before
Time Frame
week 24
Secondary Outcome Measure Information:
Title
Quantification of the HIV-1 DNA reservoir in peripheral blood monocyte cells at baseline and week 24
Time Frame
week 24
Title
Emergence of genotypic resistance in plasma HIV-1 RNA in case of virological failure
Time Frame
week 24
Title
Quantification HIV-1 RNA levels in the CSF and semen at baseline and week 24
Description
Lumbar puncture is optional at baseline
Time Frame
week 24
Title
Change from baseline CD4 cell count from baseline at week 24
Time Frame
week 24
Title
Adherence to medication at weeks 4, 8, 12, 16, 20, 24
Description
Number of participants with suboptimal adherence defined as more than 3 pills (10%) remaining from previous monthly visit OR missed more than one dose in a row OR missed dose more than once every two weeks
Time Frame
week 24
Title
Lipidic profile changes from baseline at week 24
Time Frame
week 24
Title
Body fat composition as measured by dual energy x-ray absorptiometry (DXA) scan at baseline and week 24
Time Frame
week 24
Title
Change in bone mineral density from baseline to week 24
Description
Number of patients with normal bone density, osteopenia or osteoporosis as defined by DXA scans results
Time Frame
week 24
Other Pre-specified Outcome Measures:
Title
Change in immune activation from baseline to week 24 measured by highly sensitive C-reactive protein (mg/l)
Time Frame
week 24
Title
Change in immune activation from baseline to week 24 measured by cytokines (pg/ml)
Time Frame
week 24
Title
Change in immune activation from baseline to week 24 measured by d-dimers (microg/l)
Time Frame
week 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
HIV-1 infection;
Patient included in the Swiss HIV Cohort Study (SHCS);
≥ 18 years of age;
Virologically suppressed for at least 24 months on first line triple ART (changes for toxicity permitted) with at least 4 HIV-1 RNA measurements in plasma <50 copies/ml;
No history of previous failure on ART;
No documented antiretroviral drugs resistance;
No co-infection with Hepatitis B or C virus;
Effective contraception in women;
Willing to provide CSF and semen samples;
Written informed consent
Exclusion Criteria:
HIV-2 infection;
Renal dysfunction (creatinine clearance <50ml/min);
aspartate transaminase or alanine aminotransferase >5x upper limit normal;
Concomitant use of carbamazepine, oxcarbazepine, phenytoin, phenobarbital, St John's wort, rifampicin or metformin;
Previous AIDS defining conditions or active malignancy in the past five years;
Positive HIV viral load in CSF at baseline;
Known or suspected non-compliance;
Women who are pregnant or breastfeeding.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Delphine Sculier, MD
Organizational Affiliation
University Hospital, Geneva
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospitals of Geneva, HIV unit
City
Geneva
ZIP/Postal Code
1205
Country
Switzerland
12. IPD Sharing Statement
Learn more about this trial
A Pilot Study of MONOtherapy of DOlutegravir in HIV-1 Virologically Suppressed Patients
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