HIV/AIDSPhase 3MANETNCT02155101
Efficacy and Safety Study of Darunavir for the Treatment of HIV/AIDS
A Phase 3 study testing Darunavir and ART with 2 NRTIs plus LPV/r (or ATV/r) in people with HIV/AIDS, run by University of Liverpool at 1 site in Cameroon.
Trial summary
The aim of this pilot study is to assess the feasibility, efficacy and safety of Darunavir/ritonavir 800/100 mg once daily (DRV/r) monotherapy as a switch-maintenance strategy for patients receiving second-line ART at Yaoundé Central Hospital in Cameroon. Read more about this study
- Who is it for?
- Ages 21 to 70 years
- Conditions the study is for
- HIV/AIDS
- What is being tested?
- Darunavir and ART with 2 NRTIs plus LPV/r (or ATV/r)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteCameroon
- Study dates
- May 2014to Jul 2016
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 21 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects with documented HIV-1 infection.
- Male or female aged > 21 years old.
- Subjects receiving ART with 2 NRTIs + LPV/r (or ATV/r) for at least 3 months at the time of Screening 1.
- Nadir T lymphocyte cluster of differentiation 4 (CD4) >100 cells/mm3
- Plasma HIV-1 RNA <50 copies/ml at Screening 1 confirmed ideally 4-6 weeks later at Screening 2 (two results must be documented; a first result obtained up to 12 weeks earlier will be accepted).
- Subjects can comply with the protocol requirements. In particular, subjects should be willing to be followed up at least until week 24 (discontinuation prior to week 24) and for the DRV/r arm up to week 48 (discontinuation after week 24) even if they discontinue randomized treatment.
- Subjects who have voluntarily signed and dated the consent form.
Who cannot join
- Clinical or laboratory evidence of significantly decreased hepatic function or decompensation, irrespective of liver enzyme levels (liver insufficiency).
- Co-infection with hepatitis B (HBsAg positive).
- Grade 3 or 4 laboratory abnormality as defined by AIDS, including haemoglobin ≤8mg/dL; platelets ≤50 000/mm3; estimated creatinine clearance ≤60ml/ minute, aspartate aminotransferase; alanine aminotransferase and alkaline phosphatase >3 times the upper limit of normal; and total bilirubin >2.5 times the upper limit of normal; with the following exceptions unless clinical assessment foresees an immediate health risk to the subject:
- Pre-existing diabetes or asymptomatic glucose grade 3 or 4 elevations.
- Asymptomatic triglyceride or cholesterol elevations of grade 3 or 4.
- Presence of any currently active AIDS defining illness (Category C conditions according to the Centers for Disease Control Classification System for HIV Infection 1993) with the following exceptions:
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- Stable cutaneous Kaposi's Sarcoma (i.e., no internal organ involvement other than oral lesions) that is unlikely to require any form of systemic therapy during the study.
- Wasting syndrome due to HIV infection. Note: An AIDS defining illness that is not clinically stabilized for at least 30 days will be considered as currently active.
- Pregnant or breastfeeding women.
- Active substance abuse, including alcohol or recreational drugs.
- Any clinically significant disease (e.g., tuberculosis, cardiac dysfunction, pancreatitis, acute viral infections) or life threatening disease in the previous 14 days, or findings during screening of medical history or physical examination that, in the investigator's opinion, would compromise the subject's safety or outcome of the study.
- Any medical or psychiatric condition which, in the opinion of the investigator, could compromise the subject's safety or adherence to the trial protocol.
- Previously demonstrated clinically allergy or hypersensitivity to any of the excipients of the investigational medication (DRV).
- Note: DRV is a sulfonamide. Subjects who have previously experienced a sulfonamide allergy will be allowed to enter the trial. To date, no potential for cross sensitivity between drugs in the sulfonamide class and DRV has been identified in subjects participating in phase II trials.
- Participation in any other clinical trials that involve administration of antiretrovirals or other drugs within the last 4 weeks and during the participation in this trial.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Monotherapy in Africa: Evaluation of New Therapy
The aim of this pilot study is to assess the feasibility, efficacy and safety of Darunavir/ritonavir 800/100 mg once daily (DRV/r) monotherapy as a switch-maintenance strategy for patients receiving second-line ART at Yaoundé Central Hospital in Cameroon. HIV-infected adults receiving second-line antiretroviral therapy (ART) for ≥3 months with 2 nucleos(t)ide reverse transcriptase inhibitors (NRTIs) plus either lopinavir/ritonavir (LPV/r) or atazanavir/ritonavir (ATV/r) will undergo plasma HIV-1 RNA ("viral") load testing. Those with a viral load below 50 copies/ml (<50 cps/ml) will undergo a repeat test ideally 4-6 weeks later (allowed up to 12 weeks); if the viral load is confirmed as <50 cps/ml the patient will be invited to join the randomised phase of the study. Patients (n=150) will be randomised 1:2 to either continue the current triple ART regimen (n=50) or switch to DRV/r monotherapy (n=100). The primary end-point will be viral load suppression <400 cps/ml at week 24; secondary end-points will be viral load suppression <50 cps/ml at week 12 and week 24, safety, tolerability, and emergence of protease inhibitor (PI) drug-resistance. Patients will continue observational follow-up depending on the treatment arm they are randomized to. After week 48, patients will return to local standard of care. Pharmacokinetics (PK) and pharmacogenomics sub-study to correlate plasma concentrations of DRV to outcomes, HIV-1 drug resistance testing sub study to detect mutants archived at the time of first-line ART failure and measuring HIV DNA load will be performed, as well as a cost-effectiveness analysis will test the hypothesis that savings can be achieved by switching to DRV/r monotherapy without affecting quality of care. The primary virological objective is to evaluate efficacy in terms of the percentage of subjects who have plasma HIV-1 RNA levels <400 cps/ml after 24 weeks of follow-up following a switch to DRV/r monotherapy versus continuing triple therapy containing 2 NRTIs + LPV/r (or ATV/r) (FDA Snapshot method).
Study hypothesis:
we propose that maintenance therapy with DRV/r monotherapy is a feasible, effective and safe treatment option for patients receiving second-line ART in Yaoundé.
- Conditions
- HIV/AIDS
- Being tested
- Darunavir, ART with 2 NRTIs plus LPV/r (or ATV/r)
- Keywords
- Efficacy, Safety, Darunavir, HIV-1 RNA level, Cameroon
- 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.
DarunavirDrug
Also called PREZISTA
Darunavir (PREZISTA) is a film coated, oval shaped, light orange 19.1mm tablet, debossed with 400 mg on one side and TMC on the other side.
ART with 2 NRTIs plus LPV/r (or ATV/r)Drug
Also called NRTI, lopinavir/ritonavir (LPV/r), atazanavir/ritonavir (ATV/r)
Patients on second line antiretroviral therapy take 2 NRTIs and either protease inhibitor lopinavir/ritonavir or atazanavir/ritonavir.
| Study group | Role | What they receive |
|---|---|---|
| ART with 2 NRTIs plus LPV/r (or ATV/r) | Active comparator | 2 nucleos(t)ide reverse transcriptase inhibitors (NRTIs) plus either lopinavir/ritonavir (LPV/r) or atazanavir/ritonavir (ATV/r). Receives: Drug: ART with 2 NRTIs plus LPV/r (or ATV/r) |
| Darunavir | Experimental | Dosage form: Darunavir (PREZISTA) is a film coated, oval shaped, light orange 19.1mm tablet, debossed with "400 mg" on one side and TMC on the other side. Receives: Drug: Darunavir |
What is being measured
The primary outcome is the main question the study is designed to answer.
HIV-1 RNA Viral Load
Percentage of subjects who have plasma HIV-1 RNA levels <400 cps/ml after 24 weeks of follow-up following a switch to DRV/r monotherapy versus continuing triple therapy containing 2 NRTIs + LPV/r (or ATV/r) (FDA Snapshot method). The FDA 'Snapshot' algorithm evaluates HIV RNA response using only the results at the week 24 time-point which also means that rebound at earlier time-points are not classified as treatment failure, unless it lead to discontinuation prior to the week 48.
Measured: 24 weeks
Secondary outcomes (1)
HIV-1 RNA Viral Load
Percentage of subjects who have plasma HIV-1 RNA levels <50 cps/ml after 12 weeks of follow-up following a switch to DRV/r monotherapy versus continuing triple therapy containing 2 NRTIs + LPV/r (or ATV/r), using the FDA "Time to Loss of Virologic Response" method. The FDA 'Snapshot' algorithm evaluates HIV RNA response using only the results at the week 12 time-point which also means that rebound at earlier time-points are not classified as treatment failure, unless it lead to discontinuation prior to the week 48.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2014 (estimated)
- Study startMay 2014
- Primary completionJun 2016
- Study completionJul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV/AIDSStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Liverpool
- Sponsor type
- University, hospital or other
- Collaborators
- Janssen Pharmaceutica, Chantal Biya International Reference Centre for Research on Prevention and Management of HIV/AIDS, Yaounde Central Hospital
- Responsible party
- Principal investigator, Anna Maria Geretti, University of Liverpool
- Investigators
- Anna Maria Geretti, MD, PhD, Principal investigator, University of Liverpool
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02155101
- Sponsor's protocol ID
- ChantalIRCB
- Acronym
- MANET
- Status last verified
- Aug 2019
- First submitted
- 2 Jun 2014
- Last updated
- 4 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Geretti AM, Abdullahi A, Mafotsing Fopoussi O, Bonnett L, Fokom Defo V, Moudourou S, Fokam J, Kouanfack C, Torimiro J. An apparent paradox: resistance mutations in HIV-1 DNA predict improved virological responses to antiretroviral therapy. J Antimicrob Chemother. 2019 Oct 1;74(10):3011-3015. doi: 10.1093/jac/dkz264.
PubMed 31299067
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Monotherapy in Africa: Evaluation of New Therapy
- ClinicalTrials.gov ID
- NCT02155101
- Acronym / sponsor ID
- MANET / ChantalIRCB
- Conditions
- HIV/AIDS
- Keywords
- Efficacy, Safety, Darunavir, HIV-1 RNA level, Cameroon
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- University of LiverpoolUniversity, hospital or other
- Collaborators
- Janssen Pharmaceutica, Chantal Biya International Reference Centre for Research on Prevention and Management of HIV/AIDS, Yaounde Central Hospital
- Study start
- May 2014
- Primary completion
- Jun 2016 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 4 Jun 2014 (estimated)
- Results
- Posted 4 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of this pilot study is to assess the feasibility, efficacy and safety of Darunavir/ritonavir 800/100 mg once daily (DRV/r) monotherapy as a switch-maintenance strategy for patients receiving second-line ART at Yaoundé Central Hospital in Cameroon. HIV-infected adults receiving second-line antiretroviral therapy (ART) for ≥3 months with 2 nucleos(t)ide reverse transcriptase inhibitors (NRTIs) plus either lopinavir/ritonavir (LPV/r) or atazanavir/ritonavir (ATV/r) will undergo plasma HIV-1 RNA ("viral") load testing. Those with a viral load below 50 copies/ml (<50 cps/ml) will undergo a repeat test ideally 4-6 weeks later (allowed up to 12 weeks); if the viral load is confirmed as <50 cps/ml the patient will be invited to join the randomised phase of the study. Patients (n=150) will be randomised 1:2 to either continue the current triple ART regimen (n=50) or switch to DRV/r monotherapy (n=100). The primary end-point will be viral load suppression <400 cps/ml at week 24; secondary end-points will be viral load suppression <50 cps/ml at week 12 and week 24, safety, tolerability, and emergence of protease inhibitor (PI) drug-resistance. Patients will continue observational follow-up depending on the treatment arm they are randomized to. After week 48, patients will return to local standard of care. Pharmacokinetics (PK) and pharmacogenomics sub-study to correlate plasma concentrations of DRV to outcomes, HIV-1 drug resistance testing sub study to detect mutants archived at the time of first-line ART failure and measuring HIV DNA load will be performed, as well as a cost-effectiveness analysis will test the hypothesis that savings can be achieved by switching to DRV/r monotherapy without affecting quality of care. The primary virological objective is to evaluate efficacy in terms of the percentage of subjects who have plasma HIV-1 RNA levels <400 cps/ml after 24 weeks of follow-up following a switch to DRV/r monotherapy versus continuing triple therapy containing 2 NRTIs + LPV/r (or ATV/r) (FDA Snapshot method).
Study hypothesis:
we propose that maintenance therapy with DRV/r monotherapy is a feasible, effective and safe treatment option for patients receiving second-line ART in Yaoundé.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ART with 2 NRTIs plus LPV/r (or ATV/r) | Active comparator | Drug: ART with 2 NRTIs plus LPV/r (or ATV/r)2 nucleos(t)ide reverse transcriptase inhibitors (NRTIs) plus either lopinavir/ritonavir (LPV/r) or atazanavir/ritonavir (ATV/r). |
| Darunavir | Experimental | Drug: DarunavirDosage form: Darunavir (PREZISTA) is a film coated, oval shaped, light orange 19.1mm tablet, debossed with "400 mg" on one side and TMC on the other side. |
Who may qualify
- Ages
- 21 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Subjects with documented HIV-1 infection.
- Male or female aged > 21 years old.
- Subjects receiving ART with 2 NRTIs + LPV/r (or ATV/r) for at least 3 months at the time of Screening 1.
- Nadir T lymphocyte cluster of differentiation 4 (CD4) >100 cells/mm3
- Plasma HIV-1 RNA <50 copies/ml at Screening 1 confirmed ideally 4-6 weeks later at Screening 2 (two results must be documented; a first result obtained up to 12 weeks earlier will be accepted).
Key exclusion criteria (15 listed)
- Clinical or laboratory evidence of significantly decreased hepatic function or decompensation, irrespective of liver enzyme levels (liver insufficiency).
- Co-infection with hepatitis B (HBsAg positive).
- Grade 3 or 4 laboratory abnormality as defined by AIDS, including haemoglobin ≤8mg/dL; platelets ≤50 000/mm3; estimated creatinine clearance ≤60ml/ minute, aspartate aminotransferase; alanine aminotransferase and alkaline phosphatase >3 times the upper limit of normal; and total bilirubin >2.5 times the upper limit of normal; with the following exceptions unless clinical assessment foresees an immediate health risk to the subject:
- Presence of any currently active AIDS defining illness (Category C conditions according to the Centers for Disease Control Classification System for HIV Infection 1993) with the following exceptions:
- Pregnant or breastfeeding women.
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 |
|---|---|---|
| DarunavirAlso: PREZISTADarunavir (PREZISTA) is a film coated, oval shaped, light orange 19.1mm tablet, debossed with 400 mg on one side and TMC on the other side. | Drug | Darunavir |
| ART with 2 NRTIs plus LPV/r (or ATV/r)Also: NRTI, lopinavir/ritonavir (LPV/r), atazanavir/ritonavir (ATV/r)Patients on second line antiretroviral therapy take 2 NRTIs and either protease inhibitor lopinavir/ritonavir or atazanavir/ritonavir. | Drug | ART with 2 NRTIs plus LPV/r (or ATV/r) |
Primary outcome
HIV-1 RNA Viral Load
Time frame: 24 weeks
Percentage of subjects who have plasma HIV-1 RNA levels <400 cps/ml after 24 weeks of follow-up following a switch to DRV/r monotherapy versus continuing triple therapy containing 2 NRTIs + LPV/r (or ATV/r) (FDA Snapshot method). The FDA 'Snapshot' algorithm evaluates HIV RNA response using only the results at the week 24 time-point which also means that rebound at earlier time-points are not classified as treatment failure, unless it lead to discontinuation prior to the week 48.
1 secondary outcome
HIV-1 RNA Viral Load
Time frame: 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31299067Geretti AM, Abdullahi A, Mafotsing Fopoussi O, Bonnett L, Fokom Defo V, Moudourou S, Fokam J, Kouanfack C, Torimiro J. An apparent paradox: resistance mutations in HIV-1 DNA predict improved virological responses to antiretroviral therapy. J Antimicrob Chemother. 2019 Oct 1;74(10):3011-3015. doi: 10.1093/jac/dkz264.
- Individual participant dataSharing planned: Undecided
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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.
Anna Maria Geretti, MD, PhD principal investigator
University of Liverpool
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Darunavir and ART with 2 NRTIs plus LPV/r (or ATV/r) in people with HIV/AIDS, run by University of Liverpool at 1 site in Cameroon.
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 7 inclusion and 15 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: finished, as of the sponsor's last update on 4 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Cameroon. 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 phase mean?
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?
Yes. Results are posted in the registry (first posted 4 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
HIV-1 RNA Viral Load (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02155101, which also lists 1 linked publication.
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 4 Sep 2019.