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

NCT04064632 | Unknown Phase 4

• 1 other identifier: PG23-1
• Study Type: interventional
• Target: 1,609
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV Infection

Keywords

Switch therapy; HIV; Dual ART; Rilpivirine; Darunavir/cobicistat; NNRTI; PI; virologically suppressed patients

Outcome Measures

Primary Outcomes (3)

• clinical response

  proportion of patients with HIV-RNA \< 50 copies/ml (FDA snapshot)

  24 weeks

• Virological response

  proportion of patients with HIV-RNA \> 50 copies/ml (FDA snapshot)

  24 weeks

• clinical response

  proportion of patients with HIV-RNA \< 50 copies/ml

  48 weeks

Secondary Outcomes (4)

• Tolerability (number and proportion of AEs)

  24 weeks

• Tolerability (number and proportion of AEs)

  48 weeks

• Bone mineral density

  24 weeks

• Bone mineral density

  48 weeks

Study Arms (2)

RPV +DRV/cobi

EXPERIMENTAL

The experimental receives rilpivirine (a tablet/day) and cobicistat/darunavir co-formulated tablets (a tablet day) since randomization.

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).

Drug: Rilpivirine + darunavir/cobicistat

Interventions

Rilpivirine + darunavir/cobicistat DRUG

Switch to a dual ART

RPV +DRV/cobi; baseline therapy (CAR)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• A.O. Ospedale Papa Giovanni XXIII: lead
• San Raffaele University Hospital, Italy: collaborator

Study Sites (1)

Antiviral Therapy Unit, Ospedali Riuniti

Bergamo, 24128, Italy

Location

Related Publications (2)

• 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.

  PMID: 35485333 DERIVED

• 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.

  PMID: 32129855 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Rilpivirine; Darunavir; Cobicistat

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Sulfonamides; Amides; Carbamates; Acids, Acyclic; Carboxylic Acids; Sulfones; Sulfur Compounds; Furans; Thiazoles; Azoles

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Managing Director

Model Details: 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.

Study Record Dates

• First Submitted: August 13, 2019
• First Posted: August 22, 2019
• Study Start: February 1, 2017
• Primary Completion: June 13, 2019
• Study Completion: November 30, 2019
• Last Updated: August 22, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)