HIV InfectionPhase 4PROBE2NCT04064632
RPV+DRV/Cobi Dual Therapy in Subjects With HIV Controlled Infection
A Phase 4 study testing Rilpivirine + darunavir/cobicistat in people with HIV Infection, run by A.O. Ospedale Papa Giovanni XXIII at 1 site in Italy.
Trial summary
This study evaluates efficacy and safety of rilpivirine as substitutive agent for the nucleosidic backbone of HAART in virologic suppressed patients when combined with cobicistat-boosted darunavir. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infection
- What is being tested?
- Rilpivirine + darunavir/cobicistat
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,609 participants
- Where
- 1 siteItaly
- Study dates
- 1 Feb 2017to 30 Nov 2019
- Phase
- Phase 4
- 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
- Written signed and dated informed consent to participate in the study must be given by the subject, in accordance with the International Conference of Harmonisation (ICH) Good Clinical Practice (GCP) Guideline E627 and applicable regulations, before completing any procedure related to the study.
- HIV-1 documented infection
- Male and female subjects > 18 years of age.
- Males, or non-pregnant, non-lactating females of childbearing potential, as demonstrated by a negative pregnancy test, who agree to comply with any applicable contraceptive requirements of the protocol. Women of child-bearing potential with a negative pregnancy test at Screening and Day 1 should agree to use one of the following methods: Complete abstinence from penile-vaginal intercourse from 2 weeks prior to administration of IMP, throughout the study, and for at least 2 weeks after; Double barrier method (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide) IUD and male condom Male partner sterilization confirmed and male condom Approved hormonal contraception and male condom Any other method with published data showing that the expected failure rate is <1% per year and use male condo Any contraception method must be used for at least 2 weeks after discontinuation of IMP.
- Being on a stable therapy for at least 6 months.
- SBR must be based on any 2NRTI plus a third NNRTI, PI or INI agent. Any possible registered drug is allowed among NRTI (e.g. tenofovir, lamivudine, emtricitabine and abacavir), PI (e.g. lopinavir, atazanavir, darunavir), NNRTI (efavirenz, nevirapine, rilpivirine) or INI (raltegravir, elvitegravir, dolutegravir).
- Having a fully suppressed HIV replication as documented by 2 prior HIV-RNA tests (at least two months apart) below the detection limit (50 copies/ml).
- Subjects and investigator must agree that participation in this study is in the best interest of the subject.
Who cannot join
- Patients co-infected with HBV
- Pregnancy or breast feeding.
- Positive anamnesis for allergy to NNRTI
- A positive historical genotypic test showing resistance-inducing mutation either toward NNRTIs or PIs
- History or other evidence of severe illness (malignancy or OI) requiring active treatment and/or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study.
- Anticipated need for Hepatitis C virus (HCV) therapy during the study period
Show all 13Show fewer
- Treatment with any of the following agents within 28 days of Screening: radiation therapy; cytotoxic chemotherapeutic agents; any immunomodulators that alter immune responses
- All conditions and medicinal products listed in contraindications of DRV/c and rilpivirine
- Subjects with current or prior (previous year) history of alcohol or other substance abuse.
- Patients who have previously been screened for or enrolled into this study and subsequently withdrawn.
- Patients having been given investigational drugs within 12 weeks prior to screening.
- Inability or unwillingness to provide informed consent.
- Life expectancy < 18 months
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Multicenter, National, Prospective, Open Label, Randomized, Pilot, Proof-of-concept Study on the Use of Rilpivirine Plus Darunavir/Cobicistat as Substitutive Agents in Virologic Suppressed Patients
This study evaluates efficacy and safety of rilpivirine as substitutive agent for the nucleosidic backbone of HAART in virologic suppressed patients when combined with cobicistat-boosted darunavir.
Read the detailed description
HAART is generally based on the combination of three active drugs. Two of them, usually defined the backbone, belong to the nucleosidic analogues class (NRTI). In the last years, drugs of this class have been associated to several long-term adverse events of HAART such as lipoatrophy, cardiovascular diseases, bone and kidney toxicity. Furthermore the need of a triple drug regimen has recently been questioned as maintenance therapy in well controlled chronically treated subjects. In this setting, less drug regimens (LDR) have been proposed. LDR would allow a reduced exposure to drugs and eventually limit drug-drug interactions, drug-related toxicities and would allow treatment simplification so to enhance HAART acceptability, tolerability and persistence.
- Conditions
- HIV Infection
- Being tested
- Rilpivirine + darunavir/cobicistat
- Keywords
- Switch therapy, HIV, Dual ART, Rilpivirine, Darunavir/cobicistat, NNRTI, PI, virologically suppressed patients
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rilpivirine + darunavir/cobicistatDrug
Switch to a dual ART
| Study group | Role | What they receive |
|---|---|---|
| RPV +DRV/cobi | Experimental | The experimental receives rilpivirine (a tablet/day) and cobicistat/darunavir co-formulated tablets (a tablet day) since randomization. Receives: Drug: Rilpivirine + darunavir/cobicistat |
| baseline therapy (CAR) | Active comparator | The control arm continues the baseline therapy (CAR) based on 3 drugs (2 NRTIs) for 24 weeks and then will be switched to receive rilpivirine (a tablet/day) and cobicistat/darunavir co-formulated tablets (a tablet day). Receives: Drug: Rilpivirine + darunavir/cobicistat |
What is being measured
The primary outcome is the main question the study is designed to answer.
clinical response
proportion of patients with HIV-RNA < 50 copies/ml (FDA snapshot)
Measured: 24 weeks
Virological response
proportion of patients with HIV-RNA > 50 copies/ml (FDA snapshot)
Measured: 24 weeks
clinical response
proportion of patients with HIV-RNA < 50 copies/ml
Measured: 48 weeks
Secondary outcomes (4)
Tolerability (number and proportion of AEs)
AEs total, drug related and leading to treatment interruption/change
Measured: 24 weeks
Tolerability (number and proportion of AEs)
AEs total, drug related and leading to treatment interruption/change
Measured: 48 weeks
Bone mineral density
change in bone stiffness
Measured: 24 weeks
Bone mineral density
change in bone stiffness
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 posted22 Aug 2019
- Study start1 Feb 2017
- Primary completion13 Jun 2019
- Study completion30 Nov 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients are randomly allocated into two arms: The control arm continues the baseline therapy based on 3 drugs (2 NRTIs) for 24 weeks and then will be switched to receive rilpivirine and cobicistat/darunavir co-formulated tablets (a tablet day). The experimental arm receives rilpivirine and cobicistat/darunavir coformulated tablets at randomization.
- Masking
- None (open label)
- Enrolment
- 1,609 participants (actual)
Sponsor and investigators
- Lead sponsor
- A.O. Ospedale Papa Giovanni XXIII
- Sponsor type
- University, hospital or other
- Collaborators
- San Raffaele University Hospital, Italy
- Responsible party
- Principal investigator, Franco Maggiolo, A.O. Ospedale Papa Giovanni XXIII
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04064632
- Sponsor's protocol ID
- PG23-1
- Acronym
- PROBE2
- Status last verified
- Aug 2019
- First submitted
- 13 Aug 2019
- Last updated
- 22 Aug 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Maggiolo F, Gianotti N, Comi L, Di Filippo E, Fumagalli L, Nozza S, Galli L, Valenti D, Rizzi M, Castagna A. Rilpivirine plus cobicistat-boosted darunavir as alternative to standard three-drug therapy in HIV-infected, virologically suppressed subjects: Final results of the PROBE 2 trial. Antivir Ther. 2021 May;26(3-5):51-57. doi: 10.1177/13596535211042226. Epub 2021 Oct 27.
PubMed 35485333Maggiolo F, Gianotti N, Comi L, Di Filippo E, Fumagalli L, Nozza S, Galli L, Valenti D, Rizzi M, Castagna A. Rilpivirine plus cobicistat-boosted darunavir as a two-drug switch regimen in HIV-infected, virologically suppressed subjects on steady standard three-drug therapy: a randomized, controlled, non-inferiority trial (PROBE 2). J Antimicrob Chemother. 2020 May 1;75(5):1332-1337. doi: 10.1093/jac/dkaa018.
PubMed 32129855
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter, National, Prospective, Open Label, Randomized, Pilot, Proof-of-concept Study on the Use of Rilpivirine Plus Darunavir/Cobicistat as Substitutive Agents in Virologic Suppressed Patients
- ClinicalTrials.gov ID
- NCT04064632
- Acronym / sponsor ID
- PROBE2 / PG23-1
- Conditions
- HIV Infection
- Keywords
- Switch therapy, HIV, Dual ART, Rilpivirine, Darunavir/cobicistat, NNRTI, PI, virologically suppressed patients
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 1,609 participants (actual)
- Lead sponsor
- A.O. Ospedale Papa Giovanni XXIIIUniversity, hospital or other
- Collaborators
- San Raffaele University Hospital, Italy
- Study start
- 1 Feb 2017 (actual)
- Primary completion
- 13 Jun 2019 (actual)
- Study completion
- 30 Nov 2019 (estimated)
- First posted
- 22 Aug 2019 (actual)
- 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 study evaluates efficacy and safety of rilpivirine as substitutive agent for the nucleosidic backbone of HAART in virologic suppressed patients when combined with cobicistat-boosted darunavir.
Detailed description
HAART is generally based on the combination of three active drugs. Two of them, usually defined the backbone, belong to the nucleosidic analogues class (NRTI). In the last years, drugs of this class have been associated to several long-term adverse events of HAART such as lipoatrophy, cardiovascular diseases, bone and kidney toxicity. Furthermore the need of a triple drug regimen has recently been questioned as maintenance therapy in well controlled chronically treated subjects. In this setting, less drug regimens (LDR) have been proposed. LDR would allow a reduced exposure to drugs and eventually limit drug-drug interactions, drug-related toxicities and would allow treatment simplification so to enhance HAART acceptability, tolerability and persistence.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Patients are randomly allocated into two arms: The control arm continues the baseline therapy based on 3 drugs (2 NRTIs) for 24 weeks and then will be switched to receive rilpivirine and cobicistat/darunavir co-formulated tablets (a tablet day). The experimental arm receives rilpivirine and cobicistat/darunavir coformulated tablets at randomization.
| Arm | Type | Receives |
|---|---|---|
| RPV +DRV/cobi | Experimental | Drug: Rilpivirine + darunavir/cobicistatThe experimental receives rilpivirine (a tablet/day) and cobicistat/darunavir co-formulated tablets (a tablet day) since randomization. |
| baseline therapy (CAR) | Active comparator | Drug: Rilpivirine + darunavir/cobicistatThe control arm continues the baseline therapy (CAR) based on 3 drugs (2 NRTIs) for 24 weeks and then will be switched to receive rilpivirine (a tablet/day) and cobicistat/darunavir co-formulated tablets (a tablet day). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Written signed and dated informed consent to participate in the study must be given by the subject, in accordance with the International Conference of Harmonisation (ICH) Good Clinical Practice (GCP) Guideline E627 and applicable regulations, before completing any procedure related to the study.
- HIV-1 documented infection
- Male and female subjects > 18 years of age.
- Males, or non-pregnant, non-lactating females of childbearing potential, as demonstrated by a negative pregnancy test, who agree to comply with any applicable contraceptive requirements of the protocol. Women of child-bearing potential with a negative pregnancy test at Screening and Day 1 should agree to use one of the following methods: Complete abstinence from penile-vaginal intercourse from 2 weeks prior to administration of IMP, throughout the study, and for at least 2 weeks after; Double barrier method (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide) IUD and male condom Male partner sterilization confirmed and male condom Approved hormonal contraception and male condom Any other method with published data showing that the expected failure rate is <1% per year and use male condo Any contraception method must be used for at least 2 weeks after discontinuation of IMP.
- Being on a stable therapy for at least 6 months.
Key exclusion criteria (13 listed)
- Patients co-infected with HBV
- Pregnancy or breast feeding.
- Positive anamnesis for allergy to NNRTI
- A positive historical genotypic test showing resistance-inducing mutation either toward NNRTIs or PIs
- History or other evidence of severe illness (malignancy or OI) requiring active treatment and/or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study.
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 |
|---|---|---|
| Rilpivirine + darunavir/cobicistatSwitch to a dual ART | Drug | RPV +DRV/cobi, baseline therapy (CAR) |
Primary outcome
clinical response
Time frame: 24 weeks
proportion of patients with HIV-RNA < 50 copies/ml (FDA snapshot)
Virological response
Time frame: 24 weeks
proportion of patients with HIV-RNA > 50 copies/ml (FDA snapshot)
clinical response
Time frame: 48 weeks
proportion of patients with HIV-RNA < 50 copies/ml
4 secondary outcomes
Tolerability (number and proportion of AEs)
Time frame: 24 weeks
Tolerability (number and proportion of AEs)
Time frame: 48 weeks
Bone mineral density
Time frame: 24 weeks
Bone mineral density
Time frame: 48 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2019.
- Derived from this study: PubMed 35485333Maggiolo F, Gianotti N, Comi L, Di Filippo E, Fumagalli L, Nozza S, Galli L, Valenti D, Rizzi M, Castagna A. Rilpivirine plus cobicistat-boosted darunavir as alternative to standard three-drug therapy in HIV-infected, virologically suppressed subjects: Final results of the PROBE 2 trial. Antivir Ther. 2021 May;26(3-5):51-57. doi: 10.1177/13596535211042226. Epub 2021 Oct 27.
- Derived from this study: PubMed 32129855Maggiolo F, Gianotti N, Comi L, Di Filippo E, Fumagalli L, Nozza S, Galli L, Valenti D, Rizzi M, Castagna A. Rilpivirine plus cobicistat-boosted darunavir as a two-drug switch regimen in HIV-infected, virologically suppressed subjects on steady standard three-drug therapy: a randomized, controlled, non-inferiority trial (PROBE 2). J Antimicrob Chemother. 2020 May 1;75(5):1332-1337. doi: 10.1093/jac/dkaa018.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Rilpivirine + darunavir/cobicistat in people with HIV Infection, run by A.O. Ospedale Papa Giovanni XXIII at 1 site in Italy.
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 8 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: status not confirmed, as of the sponsor's last update on 22 Aug 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 Italy. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
clinical response (time frame: 24 weeks). The study lists 3 primary outcomes in all. 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 NCT04064632, which also lists 2 linked publications.
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 22 Aug 2019.