HIV/AIDSPhase 2/3TMC114HIV2030NCT02499978
Darunavir/Cobicistat and Dolutegravir to Maintain Virologic Suppression and Reduce NRTI-associated Toxicity
A Phase 2/3 study testing Darunavir/Cobicistat and Dolutegravir in people with HIV/AIDS, run by Stanford University at 2 sites in United States.
Trial summary
This is a clinical research study to see if switching to Darunavir/Cobicistat ((PREZCOBIX™, DRV/COBI ) and Dolutegrivir (Tivicay®, DTG) in HIV-infected individuals with undetectable HIV viral load on nucleos(t)ide reverse transcriptase inhibitor (NRTI)-containing therapy will be effective in maintaining virologic… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV/AIDS
- What is being tested?
- Darunavir/Cobicistat and Dolutegravir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 2 sitesUnited States
- Study dates
- May 2016to Jun 2016
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. HIV-1 infection, as documented by any licensed ELISA test kit and confirmed by Western blot at any time prior to study entry. A second antibody test by a method other than ELISA is acceptable as an alternative confirmatory test or a previous detectable HIV RNA level.
- 2 .Age ≥ 18 years
- 3. HIV-1 RNA <50 copies/mL while on a stable antiretroviral regimen for at least 6 months prior to study entry excluding blips (i.e., a single measurement <200 copies/mL preceded and followed by measurements <50 copies/mL)
- 4. At screening, patient on a stable antiretroviral regimen containing at least one NRTI and a PI, NNRTI, or INSTI
- 5. No changes in antiretroviral regimen in the six months prior to screening (except for a switch to a coformulated tablet from the component tablets)
- 6. A desire to switch off current antiretroviral therapy due to: a) Renal dysfunction (microalbuminuria/proteinuria or CrCl<70 mL/min/1.73 m2) on tenofovir disoproxil fumarate (TDF) of tenofovir al; b) Osteopenia or osteoporosis on a TDF-containing regimen (i.e., lowest T-score ≥1.0 standard deviation below the young adult mean measured by dual-energy x-ray absorptiometry); c) Peripheral neuropathy or lipoatrophy at least partially attributable to ongoing NRTI use; d) Intermediate or high Framingham risk (i.e., ≥10% 10-year risk) on an abacavir-containing regimen; e) Patient preference.
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- 7. Laboratory values within six months of screening visit
- Hemoglobin ≥8.0 g/dL
- Platelet count ≥40,000/mm3
- AST, ALT, and alkaline phosphatase ≤5 × ULN
- Total bilirubin ≤2.5 x ULN (except for those on atazanavir-containing regimens)
- Calculated creatinine clearance (CrCl) ≥45 mL/min as estimated by the Cockcroft-Gault equation:
- For men, (140 - age in years) x (body weight in kg) ÷ (serum creatinine in mg/dL x 72) = CrCl (mL/min)
- For women, multiply the result by 0.85 = CrCl (mL/min)
- 8. For women of reproductive potential, negative serum or urine pregnancy test at screening and a negative urine pregnancy test at the entry visit prior to randomization and also agreeable to using a contraceptive of choice during the study period.
- "Women of reproductive potential" are defined as women who have not been post-menopausal for at least 24 consecutive months (i.e., who have had menses within the preceding 24 months) and have not undergone surgical sterilization (i.e., hysterectomy, bilateral oophorectomy, or tubal ligation)
Who cannot join
- Current CD4+ T-cell count <200 cells/µL
- Current antiretroviral regimen consisting of three of more antiretroviral classes
- History of genotypic resistance, phenotypic resistance or intolerance to either DRV or DTG.
- Prohibited protease mutations: V11I, V32I, L33F, I47V/A/L, I50V, I54T/S/L/M, T74P, L76V, V82F, I84V, or L89V
- Prohibited INSTI mutations: E92Q, E92K/A, G140S/A/C, Q148H/R/K or Q148 substitution plus any of the following: L74I/M, E138A/D/K/T, G140A/S, Y143H/R, E157Q, G163E/K/Q/R/S, or G193E/R.
- History of virologic failure while on an INSTI prior to study enrollment
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- Severe hepatic impairment (Child Pugh Class C)
- Hepatitis B Surface Antigen Positive
- Breastfeeding, pregnancy, or plans to become pregnant during the study
- Known allergy/sensitivity to any study drug or their formulations.
- Receipt or planned receipt of prohibited concomitant medications (See section 5.2.1)
- Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study procedures and treatment.
- Serious medical illness that, in the opinion of the site investigator, precludes safe participation in the study.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Colorado
Aurora, Colorado, 80045
Stanford Univerity
Stanford, California, 94305
About this study
Official title: Darunavir/Cobicistat and Dolutegravir to Maintain Virologic Suppression and Reduce NRTI-associated Toxicity (The 'deNUC' Study; TMC114HIV2030)
This is a clinical research study to see if switching to Darunavir/Cobicistat ((PREZCOBIX™, DRV/COBI ) and Dolutegrivir (Tivicay®, DTG) in HIV-infected individuals with undetectable HIV viral load on nucleos(t)ide reverse transcriptase inhibitor (NRTI)-containing therapy will be effective in maintaining virologic suppression at 48 weeks of treatment.
Read the detailed description
NRTIs have been a stalwart for treatment in both the pre- and post-ART eras. However, NRTIs have numerous toxicities partly due to the fact that they are analogs of naturally occurring nucleotides and interfere with the activity of numerous cellular functions. In highly treatment-experienced individuals with more than two active drugs in their salvage regimens, an NRTI-sparing regimen has been shown to be non-inferior to an NRTI-containing regimen [33]. However, studies with NRTI-sparing regimens not consisting of more than two active medications have generally been disappointing.
One limitation of earlier NRTI-sparing regimens has been a higher pill burden than more standard regimens. However, the approvals of DTG and the co-formulated DRV/COBI, both with well-established antiviral activities, may allow for a compact, effective, NRTI-sparing regimen. A switch to DTG/DRV/COBI in virologically suppressed HIV-infected individuals has the potential to avoid NRTI-associated toxicity while maintaining virologic suppression.
- Conditions
- HIV/AIDS
- Being tested
- Darunavir/Cobicistat, Dolutegravir
- Medical subject headings
- Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Darunavir/CobicistatDrug
Also called Prezcobix, DRV/COBI
Fixed dose combination medication
DolutegravirDrug
Also called Tivicay, DTG
single tablet medication
| Study group | Role | What they receive |
|---|---|---|
| DRV/COBI, DTG Immediate switch | Experimental | DARUNAVIR/COBICISTAT (800mg/150MG), DOLUTEGRAVIR 50MG DAILY at randomization and follow through week 48. Receives: Drug: Darunavir/Cobicistat; Drug: Dolutegravir |
| DRV/COBI, DTG Delayed Switch | Active comparator | DARUNAVIR/COBICISTAT (800MG150MG), DOLUTEGRAVIR 50MG DAILY at week 24 and follow through week 48. Receives: Drug: Darunavir/Cobicistat; Drug: Dolutegravir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Virologic suppression (24 weeks)
Compare between arms the proportion of patients maintaining virologic suppression (i.e., no confirmed HIV RNA levels ≥200 copies/mL) at Week 24
Measured: 24 weeks
Secondary outcomes (1)
Virologic Suppression (48 weeks)
Evaluate the proportion of participants who maintain virologic suppression 24 weeks post-switch (i.e. at 24 weeks in the immediate switch arm and at 48 weeks in the delayed switch arm)
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2015 (estimated)
- Study startMay 2016
- Primary completionJun 2016
- Study completionJun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV/AIDSStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- Janssen Scientific Affairs, LLC, University of Colorado, Denver
- Responsible party
- Principal investigator, Philip Grant, Stanford University
- Investigators
- Philip Grant, MD, Study director, Stanford UniversitySean Collins, MD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02499978
- Sponsor's protocol ID
- deNUC
- Acronym
- TMC114HIV2030
- Status last verified
- Oct 2016
- First submitted
- 14 Jul 2015
- Last updated
- 9 Jul 2021
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Darunavir/Cobicistat and Dolutegravir to Maintain Virologic Suppression and Reduce NRTI-associated Toxicity (The 'deNUC' Study; TMC114HIV2030)
- ClinicalTrials.gov ID
- NCT02499978
- Acronym / sponsor ID
- TMC114HIV2030 / deNUC
- Conditions
- HIV/AIDS
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- Janssen Scientific Affairs, LLC, University of Colorado, Denver
- Study start
- May 2016
- Primary completion
- Jun 2016 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 16 Jul 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a clinical research study to see if switching to Darunavir/Cobicistat ((PREZCOBIX™, DRV/COBI ) and Dolutegrivir (Tivicay®, DTG) in HIV-infected individuals with undetectable HIV viral load on nucleos(t)ide reverse transcriptase inhibitor (NRTI)-containing therapy will be effective in maintaining virologic suppression at 48 weeks of treatment.
Detailed description
NRTIs have been a stalwart for treatment in both the pre- and post-ART eras. However, NRTIs have numerous toxicities partly due to the fact that they are analogs of naturally occurring nucleotides and interfere with the activity of numerous cellular functions. In highly treatment-experienced individuals with more than two active drugs in their salvage regimens, an NRTI-sparing regimen has been shown to be non-inferior to an NRTI-containing regimen [33]. However, studies with NRTI-sparing regimens not consisting of more than two active medications have generally been disappointing.
One limitation of earlier NRTI-sparing regimens has been a higher pill burden than more standard regimens. However, the approvals of DTG and the co-formulated DRV/COBI, both with well-established antiviral activities, may allow for a compact, effective, NRTI-sparing regimen. A switch to DTG/DRV/COBI in virologically suppressed HIV-infected individuals has the potential to avoid NRTI-associated toxicity while maintaining virologic suppression.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| DRV/COBI, DTG Immediate switch | Experimental | Drug: Darunavir/Cobicistat, Drug: DolutegravirDARUNAVIR/COBICISTAT (800mg/150MG), DOLUTEGRAVIR 50MG DAILY at randomization and follow through week 48. |
| DRV/COBI, DTG Delayed Switch | Active comparator | Drug: Darunavir/Cobicistat, Drug: DolutegravirDARUNAVIR/COBICISTAT (800MG150MG), DOLUTEGRAVIR 50MG DAILY at week 24 and follow through week 48. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 1. HIV-1 infection, as documented by any licensed ELISA test kit and confirmed by Western blot at any time prior to study entry. A second antibody test by a method other than ELISA is acceptable as an alternative confirmatory test or a previous detectable HIV RNA level.
- 2 .Age ≥ 18 years
- 3. HIV-1 RNA <50 copies/mL while on a stable antiretroviral regimen for at least 6 months prior to study entry excluding blips (i.e., a single measurement <200 copies/mL preceded and followed by measurements <50 copies/mL)
- 4. At screening, patient on a stable antiretroviral regimen containing at least one NRTI and a PI, NNRTI, or INSTI
- 5. No changes in antiretroviral regimen in the six months prior to screening (except for a switch to a coformulated tablet from the component tablets)
Key exclusion criteria (13 listed)
- Current CD4+ T-cell count <200 cells/µL
- Current antiretroviral regimen consisting of three of more antiretroviral classes
- History of genotypic resistance, phenotypic resistance or intolerance to either DRV or DTG.
- Prohibited protease mutations: V11I, V32I, L33F, I47V/A/L, I50V, I54T/S/L/M, T74P, L76V, V82F, I84V, or L89V
- Prohibited INSTI mutations: E92Q, E92K/A, G140S/A/C, Q148H/R/K or Q148 substitution plus any of the following: L74I/M, E138A/D/K/T, G140A/S, Y143H/R, E157Q, G163E/K/Q/R/S, or G193E/R.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Darunavir/CobicistatAlso: Prezcobix, DRV/COBIFixed dose combination medication | Drug | DRV/COBI, DTG Delayed Switch, DRV/COBI, DTG Immediate switch |
| DolutegravirAlso: Tivicay, DTGsingle tablet medication | Drug | DRV/COBI, DTG Delayed Switch, DRV/COBI, DTG Immediate switch |
Primary outcome
Virologic suppression (24 weeks)
Time frame: 24 weeks
Compare between arms the proportion of patients maintaining virologic suppression (i.e., no confirmed HIV RNA levels ≥200 copies/mL) at Week 24
1 secondary outcome
Virologic Suppression (48 weeks)
Time frame: 48 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Philip Grant, MD study director
Stanford University
Sean Collins, MD principal investigator
Stanford University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Darunavir/Cobicistat and Dolutegravir in people with HIV/AIDS, run by Stanford University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 9 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Virologic suppression (24 weeks) (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jul 2021.