- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04064632
RPV+DRV/Cobi Dual Therapy in Subjects With HIV Controlled Infection (PROBE2)
August 19, 2019 updated by: Franco Maggiolo, A.O. Ospedale Papa Giovanni XXIII
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.
Study Overview
Status
Unknown
Conditions
Intervention / Treatment
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 Type
Interventional
Enrollment (Actual)
1609
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Bergamo, Italy, 24128
- Antiviral Therapy Unit, Ospedali Riuniti
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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
- 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: RPV +DRV/cobi
The experimental receives rilpivirine (a tablet/day) and cobicistat/darunavir co-formulated tablets (a tablet day) since randomization.
|
Switch to a dual ART
|
Active Comparator: baseline therapy (CAR)
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).
|
Switch to a dual ART
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
clinical response
Time Frame: 24 weeks
|
proportion of patients with HIV-RNA < 50 copies/ml (FDA snapshot)
|
24 weeks
|
Virological response
Time Frame: 24 weeks
|
proportion of patients with HIV-RNA > 50 copies/ml (FDA snapshot)
|
24 weeks
|
clinical response
Time Frame: 48 weeks
|
proportion of patients with HIV-RNA < 50 copies/ml
|
48 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Tolerability (number and proportion of AEs)
Time Frame: 24 weeks
|
AEs total, drug related and leading to treatment interruption/change
|
24 weeks
|
Tolerability (number and proportion of AEs)
Time Frame: 48 weeks
|
AEs total, drug related and leading to treatment interruption/change
|
48 weeks
|
Bone mineral density
Time Frame: 24 weeks
|
change in bone stiffness
|
24 weeks
|
Bone mineral density
Time Frame: 48 weeks
|
change in bone stiffness
|
48 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General 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.
- 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 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
February 1, 2017
Primary Completion (Actual)
June 13, 2019
Study Completion (Anticipated)
November 30, 2019
Study Registration Dates
First Submitted
August 13, 2019
First Submitted That Met QC Criteria
August 19, 2019
First Posted (Actual)
August 22, 2019
Study Record Updates
Last Update Posted (Actual)
August 22, 2019
Last Update Submitted That Met QC Criteria
August 19, 2019
Last Verified
August 1, 2019
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Infections
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Reverse Transcriptase Inhibitors
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Anti-HIV Agents
- Anti-Retroviral Agents
- Protease Inhibitors
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 Enzyme Inhibitors
- HIV Protease Inhibitors
- Viral Protease Inhibitors
- Cobicistat
- Darunavir
- Rilpivirine
- Cobicistat mixture with darunavir
Other Study ID Numbers
- PG23-1
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on HIV Infection
-
Erasmus Medical CenterNot yet recruitingHIV Infections | Hiv | HIV-1-infection | HIV I InfectionNetherlands
-
Sociedad Andaluza de Enfermedades InfecciosasConsejeria de Salud. Junta de Andalucia. SpainCompletedHIV Infection | HIV-1 InfectionSpain
-
Beckman Coulter, Inc.CompletedHIV I Infection | HIV-2 InfectionFrance
-
Allegheny Singer Research Institute (also known...Active, not recruitingHIV Infections | HIV-1-infection | HIV I InfectionUnited States
-
Rockefeller UniversityCompletedHIV Infection | Healthy Volunteers | HIV-1 InfectionUnited States
-
Erasmus Medical CenterRecruitingHIV Infections | HIV-1-infection | HIV-2 InfectionNetherlands
-
Erasmus Medical CenterActive, not recruitingHIV Infections | HIV-1-infection | HIV-2 InfectionNetherlands
-
AIDS Healthcare FoundationUniversity of California, Los AngelesCompleted
-
Merck Sharp & Dohme LLCCompleted
-
National Institute of Allergy and Infectious Diseases...CompletedHIV-1 Infection | HIV Antibodies | Neutralizing Antibody | Viral Load | Monoclonal AntibodyUnited States
Clinical Trials on Rilpivirine + darunavir/cobicistat
-
Therapeutic ConceptsJanssen Scientific Affairs, LLCUnknown
-
Janssen Scientific Affairs, LLCCompletedHIV Infections | Pregnancy | HIVUnited States, Puerto Rico
-
Shanghai Public Health Clinical CenterUnknownCoronavirus | Pneumonia, PneumocystisChina
-
Hamad Medical CorporationCompletedPneumonia | COVID | CoronavirusQatar
-
Janssen Research & Development, LLCCompleted
-
Janssen Pharmaceutical K.K.Completed
-
Fundación FLS de Lucha Contra el Sida, las Enfermedades...ViiV HealthcareCompleted
-
Fundación FLS de Lucha Contra el Sida, las Enfermedades...Completed
-
National Institutes of Health Clinical Center (CC)Completed
-
Stanford UniversityUniversity of Colorado, Denver; Janssen Scientific Affairs, LLCWithdrawn