Implication for Strategies of Long Term Control of Viral Replication in Patient With Primary HIV Infection (PHI).

NCT04225325 | Unknown Phase 4

• 1 other identifier: P25-INACTION
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 1

Brief Summary

Multicenter, parallel group, randomised, open label, study. Twenty-five clinical centers constituting the InAction network will participate the study. Eligible patients will be randomised in a ratio 10:10:8 to be treated with one of the three antiretroviral regimens:

• TDF/FTC 245 mg/200 mg single tablet QD + DRV /cobicistat 800 mg /150 mg single tablet QD (Arm A, standard regimen),
• TDF/FTC 245 mg/200 mg single tablet QD + DTG 50 mg QD (Arm B, standard regimen).
• TDF/FTC 245 mg/200 mg single tablet QD + DRV 800 mg /cobicistat single tablet QD + DTG 50 mg QD (Arm C, experimental regimen). One-hundred-and-twelve PHI subjects will be recruited for this study among those attending the outpatient Clinic of Infectious Diseases, Ospedale San Raffaele and other Italian centres, involved in the INACTION network.

Conditions

HIV-1-infection

Keywords

antiretroviral drugs; HIV viral reservoir; HIV acute infection

Outcome Measures

Primary Outcomes (1)

• the change of total HIV-DNA level from baseline to 48 weeks.

  The primary objective of the study is to compare the proviral DNA change in patients who started three different antiretroviral treatments.

  48 weeks

Secondary Outcomes (4)

• the proportion of patients with HIV-1 RNA <50 copies/mL

  weeks 12, 24 and 48

• time to achieve undetectable viral load

  week 12 and week 48

• change in HIV-DNA

  week 12 and week 48

• change in HIV-1 RNA in CSF

  week 12 and 48

Study Arms (3)

A: SYMTUZA

ACTIVE COMPARATOR

TAF/FTC 245 mg/200 mg single tablet QD +DRV /cobicistat 800 mg /150 mg single tablet QD

Combination Product: SYMTUZA

B: DESCOVY+DOLUTEGRAVIR

ACTIVE COMPARATOR

TAF/FTC 245 mg/200 mg single tablet QD+DTG 50 mg QD

Combination Product: DESCOVY+DOLUTEGRAVIR

C: SYMTUZA+DOLUTEGRAVIR

EXPERIMENTAL

TAF/FTC 245 mg/200 mg single tablet QD+DRV/cobicistat single tablet QD + +DTG 50 mg QD

Combination Product: SYMTUZA+DOLUTEGRAVIR

Interventions

SYMTUZA COMBINATION_PRODUCT

DESCOVY+REZOLSTA

A: SYMTUZA

DESCOVY+DOLUTEGRAVIR COMBINATION_PRODUCT

DESCOVY+DOLUTEGRAVIR

B: DESCOVY+DOLUTEGRAVIR

SYMTUZA+DOLUTEGRAVIR COMBINATION_PRODUCT

DESCOVY+REZOLSTA+DTG

C: SYMTUZA+DOLUTEGRAVIR

Eligibility Criteria

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

You may qualify if:

• Subjects must be at least 18 years of age at the time of randomization, of either sex and of any race.
• Primary HIV Infection defined according to Fiebig's classification.
• Subjects must have given written informed consent and must be able to adhere to dose and visit schedules.
• Female subjects of child-bearing potential must agree to use a medically accepted method of contraception.
• Female subjects of child-bearing potential must have a negative serum beta-hCG pregnancy test at Screening, and a negative urine beta-HCG pregnancy test on Day 1 prior to dosing.
• A female, may be eligible to enter and participate in the study if she:
• is of non-child-bearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and ≥ 45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy;
• is of child-bearing potential with a negative pregnancy test at both Screening and Day 1 and agrees to use one of the following methods of contraception to avoid pregnancy:
• Complete abstinence from penile-vaginal intercourse from 2 weeks prior to administration of IP, throughout the study, and for at least 2 weeks after discontinuation of all study medications;
• Double barrier method (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide);
• Any intrauterine device (IUD) with published data showing that the expected failure rate is \<1% per year (not all IUDs meet this criterion, see Appendix 4 for an example listing of approved IUDs);
• Male partner sterilization confirmed prior to the female subject's entry into the study, and this male is the sole partner for that subject;
• Approved hormonal contraception for subjects randomized to arm B (TDF/FTC + DTG)
• Approved hormonal contraception and a barrier method for subjects randomized to arm A (TDF/FTC +DRV/cobicistat) and C (TDF/FTC +DRV/cobicistat +DTG)
• Any other method with published data showing that the expected failure rate is \<1% per year.

You may not qualify if:

• Female subjects of childbearing potential who are breastfeeding, pregnant, or planning to become pregnant.
• Subjects with active opportunistic infection or malignancy.
• Subjects positive for Hepatitis B at screening (+HBsAg), or anticipated need for Hepatitis C virus (HCV) therapy during the study.
• Subjects with known liver cirrhosis.
• Subjects with any clinically significant condition or situation other than the condition being studied that, in the opinion of investigator, would interfere with the study evaluations or optimal participation.
• Subjects with allergy/sensitivity to drugs or its excipients.
• History or presence of allergy to the study drugs or their components
• Alanine aminotransferase (ALT) 5 times the upper limit of normal (ULN), OR ALT 3xULN and bilirubin 1.5xULN (with \>35% direct bilirubin)
• Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
• Subjects with severe hepatic impairment (Class C) as determined by Child-Pugh classification
• Subject has creatinine clearance of \<70 mL/min via Cockroft-Gault method
• Hepatic failure (Child-Plug grade C)
• Use of not modifiable concomitant drugs: carbamazepine, fenitoine, fenobarbital, rifampicine, Hypericum perforatum, dofelitide.

Sponsors & Collaborators

• ADRIANO LAZZARIN, MD: lead
• Ministero della Salute, Italy: collaborator

Study Sites (1)

Ospedale San Raffaele

Milan, MI, 20127, Italy

RECRUITING

Related Publications (1)

• Bruzzesi E, Gabrieli A, Bernasconi D, Marchetti G, Calcagno A, Ripamonti D, Antinori A, Squillace N, Cingolani A, Muscatello A, Bandera A, Gori A, Rusconi S, Nozza S; INACTION Study Group. HIV-DNA decrease during treatment in primary HIV-1 infection with three different drug regimens: Italian Network of Acute HIV Infection (INACTION) clinical trial. J Med Virol. 2023 Sep;95(9):e29114. doi: 10.1002/jmv.29114.

  PMID: 37752816 DERIVED

MeSH Terms

Interventions

symtuza

Study Officials

• GIUSEPPE TAMBUSSI

  Ospedale San Raffaele

  STUDY CHAIR

Central Study Contacts

SILVIA NOZZA

CONTACT

0226437961; nozza.silvia@hsr.it

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: HEAD OF INFECTIOUS DISEASES CLINIC

Model Details: Eligible patients will be randomised in a ratio 10:10:8 to be treated with one of the three antiretroviral regimens: * TDF/FTC 245 mg/200 mg single tablet QD + DRV /cobicistat 800 mg /150 mg single tablet QD (Arm A, standard regimen), * TDF/FTC 245 mg/200 mg single tablet QD + DTG 50 mg QD (Arm B, standard regimen). * TDF/FTC 245 mg/200 mg single tablet QD + DRV 800 mg /cobicistat single tablet QD + DTG 50 mg QD (Arm C, experimental regimen).

Study Record Dates

• First Submitted: September 16, 2019
• First Posted: January 13, 2020
• Study Start: May 7, 2018
• Primary Completion: September 30, 2019
• Study Completion: June 14, 2021
• Last Updated: January 13, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)