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RPV+DRV/Cobi Dual Therapy in Subjects With HIV Controlled Infection (PROBE2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04064632
Recruitment Status : Active, not recruiting
First Posted : August 22, 2019
Last Update Posted : August 22, 2019
Sponsor:
Collaborator:
San Raffaele University Hospital, Italy
Information provided by (Responsible Party):
Franco Maggiolo, A.O. Ospedale Papa Giovanni XXIII

Brief 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.

Condition or disease Intervention/treatment Phase
HIV Infection Drug: Rilpivirine + darunavir/cobicistat Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1609 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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)
Primary Purpose: Treatment
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
Actual Study Start Date : February 1, 2017
Actual Primary Completion Date : June 13, 2019
Estimated Study Completion Date : November 30, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

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.
Drug: Rilpivirine + darunavir/cobicistat
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).
Drug: Rilpivirine + darunavir/cobicistat
Switch to a dual ART




Primary Outcome Measures :
  1. clinical response [ Time Frame: 24 weeks ]
    proportion of patients with HIV-RNA < 50 copies/ml (FDA snapshot)

  2. Virological response [ Time Frame: 24 weeks ]
    proportion of patients with HIV-RNA > 50 copies/ml (FDA snapshot)

  3. clinical response [ Time Frame: 48 weeks ]
    proportion of patients with HIV-RNA < 50 copies/ml


Secondary Outcome Measures :
  1. Tolerability (number and proportion of AEs) [ Time Frame: 24 weeks ]
    AEs total, drug related and leading to treatment interruption/change

  2. Tolerability (number and proportion of AEs) [ Time Frame: 48 weeks ]
    AEs total, drug related and leading to treatment interruption/change

  3. Bone mineral density [ Time Frame: 24 weeks ]
    change in bone stiffness

  4. Bone mineral density [ Time Frame: 48 weeks ]
    change in bone stiffness



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.
  2. HIV-1 documented infection
  3. Male and female subjects > 18 years of age.
  4. 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.
  5. Being on a stable therapy for at least 6 months.
  6. 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).
  7. 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).
  8. Subjects and investigator must agree that participation in this study is in the best interest of the subject.

Exclusion Criteria:

  1. Patients co-infected with HBV
  2. Pregnancy or breast feeding.
  3. Positive anamnesis for allergy to NNRTI
  4. A positive historical genotypic test showing resistance-inducing mutation either toward NNRTIs or PIs
  5. 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.
  6. Anticipated need for Hepatitis C virus (HCV) therapy during the study period
  7. Treatment with any of the following agents within 28 days of Screening: radiation therapy; cytotoxic chemotherapeutic agents; any immunomodulators that alter immune responses
  8. All conditions and medicinal products listed in contraindications of DRV/c and rilpivirine
  9. Subjects with current or prior (previous year) history of alcohol or other substance abuse.
  10. Patients who have previously been screened for or enrolled into this study and subsequently withdrawn.
  11. Patients having been given investigational drugs within 12 weeks prior to screening.
  12. Inability or unwillingness to provide informed consent.
  13. Life expectancy < 18 months

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04064632


Locations
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Italy
Antiviral Therapy Unit, Ospedali Riuniti
Bergamo, Italy, 24128
Sponsors and Collaborators
A.O. Ospedale Papa Giovanni XXIII
San Raffaele University Hospital, Italy
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Responsible Party: Franco Maggiolo, Managing Director, A.O. Ospedale Papa Giovanni XXIII
ClinicalTrials.gov Identifier: NCT04064632    
Other Study ID Numbers: PG23-1
First Posted: August 22, 2019    Key Record Dates
Last Update Posted: August 22, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Franco Maggiolo, A.O. Ospedale Papa Giovanni XXIII:
Switch therapy
HIV
Dual ART
Rilpivirine
Darunavir/cobicistat
NNRTI
PI
virologically suppressed patients
Additional relevant MeSH terms:
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Infection
Darunavir
Cobicistat
Rilpivirine
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors