Rapid Reinitiation of a Single Tablet Antiretroviral Therapy Using Symtuza® in HIV-1 Infected Treatment-Experienced Patients Off Therapy. (ReSTART)

NCT04388904 | Completed Phase 4 FDA Drug

• 1 other identifier: TMC114FD2HTX4007
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to demonstrate the effectiveness of Symtuza® in a rapid reinitiation model of care in patients with HIV-1 infection and who are treatment-experienced but have been off of antiretroviral therapy (ART) for 12 or more weeks.

Conditions

HIV-1-infection

Keywords

Acquired Immunodeficiency Syndrome; HIV Infections; Sexually Transmitted Diseases, Viral; Anti-Retroviral Agents; Antiviral Agents

Outcome Measures

Primary Outcomes (1)

• The proportion of subjects who have HIV-1 RNA <50 copies/mL at week 48

  The proportion of subjects who have HIV-1 RNA \<50 copies/mL at week 48 as defined by the FDA snapshot analysis (ITT)

  48 week

Secondary Outcomes (19)

• Proportion of subjects who have HIV-1 RNA <50 copies/mL at week 48

  Week 48

• Proportion of subjects who have HIV-1 RNA <50 copies/mL at week 48

  Week 48

• Proportion of subjects who have HIV-1 RNA <200 copies/mL at week 24

  Week 24

• Change from baseline in HIV-1 RNA viral load

  Weeks 24 and 48

• Change in baseline CD4 cell count

  Weeks 12, 24, and 48

Study Arms (1)

Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (FDC)

EXPERIMENTAL

Participants will receive oral tablet containing Darunavir 800 milligram (mg)/ Cobicistat 150 mg/ Emtricitabine 200 mg/ Tenofovir Alafenamide 10 mg (D/C/F/TAF) fixed-dose combination (FDC) once daily within 24 hours of the screening/baseline visit.

Drug: Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (FDC)

Interventions

Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (FDC) DRUG

Participants will receive Symtuza®. An oral tablet containing Darunavir 800 mg /Cobicistat 150 mg /Emtricitabine 200 mg /Tenofovir Alafenamide 10 mg FDC, once daily within 24 hours of the screening/ baseline visit.

Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (FDC)

Eligibility Criteria

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

You may qualify if:

• At least 18 years of age at screening/baseline visit.
• Antiretroviral treatment-experienced and have not received any anti-HIV treatment within 12 weeks prior to screening.
• Contraceptive use by men or women should be consistent with the local regulations regarding the use of contraceptive methods for subject participating in clinical studies.
• Men must agree not to donate sperm during the study until 90 days after receiving the last dose of study drug (or longer, if dictated by local regulations).
• Must be able to swallow whole tablets or swallow tablets cut into halves.

You may not qualify if:

• Known active cryptococcal infection, active toxoplasmic encephalitis, Mycobacterium tuberculosis infection, or another AIDS-defining condition that in the judgment of the investigator would increase the risk of morbidity or mortality.
• Known resistance to any of the components of D/C/F/TAF; subjects with known or identified FTC resistance attributed to an M184V mutation alone will be permitted to remain in the study.
• Prior virologic failure on a DRV-containing regimen from known history or from medical records.
• Known history of clinically relevant hepatic disease or hepatitis that in the investigator's judgment is not compatible with D/C/F/TAF.
• Known history of severe hepatic impairment as diagnosed based on documented history of severe hepatic impairment (Child-Pugh C).
• Known history of chronic (≥3 months) renal insufficiency, defined as having an eGFR\<30 mL/min according to the MDRD formula.
• Pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study or within 90 days after the last dose of study treatment.
• Plans to father a child while enrolled in this study or within 90 days after the last dose of study treatment.
• Current alcohol or substance use judged by the investigator to potentially interfere with subject study adherence.
• Known history of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, noninvasive cutaneous squamous carcinoma.
• Known active, severe infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy that in the judgment of the investigator would increase the risk of morbidity or mortality.
• Any other condition or prior therapy for which, in the opinion of the investigator, participation would not be in the best interest of the subject (e.g., compromise the wellbeing) or that could prevent, limit, or confound the protocol-specified assessments.
• Subject unlikely to comply with the protocol requirements based on clinical judgment.
• Received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 90 days before the planned first dose of study treatment or is currently enrolled in an investigational study.
• Subjects receiving ongoing therapy with contraindicated, not recommended, drugs that cannot be adequately dose-adjusted, or subjects with any known allergies to the excipients of the D/C/F/TAF.

Sponsors & Collaborators

• The Crofoot Research Center, Inc.: lead
• Janssen Scientific Affairs, LLC: collaborator

Study Sites (1)

The Crofoot Research Center, Inc.

Houston, Texas, 77098, United States

Location

Related Publications (4)

• Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, Hakim JG, Kumwenda J, Grinsztejn B, Pilotto JH, Godbole SV, Mehendale S, Chariyalertsak S, Santos BR, Mayer KH, Hoffman IF, Eshleman SH, Piwowar-Manning E, Wang L, Makhema J, Mills LA, de Bruyn G, Sanne I, Eron J, Gallant J, Havlir D, Swindells S, Ribaudo H, Elharrar V, Burns D, Taha TE, Nielsen-Saines K, Celentano D, Essex M, Fleming TR; HPTN 052 Study Team. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011 Aug 11;365(6):493-505. doi: 10.1056/NEJMoa1105243. Epub 2011 Jul 18.

  PMID: 21767103 BACKGROUND

• Palella FJ Jr, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, Aschman DJ, Holmberg SD. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med. 1998 Mar 26;338(13):853-60. doi: 10.1056/NEJM199803263381301.

  PMID: 9516219 BACKGROUND

• Centers for Disease Control and Prevention. Monitoring selected national HIV prevention and care objectives by using HIV surveillance data-United States and 6 dependent areas, 2016. HIV Surveillance Supplemental Report 2018;23(No. 4). http://www.cdc.gov/hiv/library/reports/ hiv-surveillance.html. Accessed [February 4, 2020]

  BACKGROUND

• Horberg MA, Hurley LB, Silverberg MJ, Klein DB, Quesenberry CP, Mugavero MJ. Missed office visits and risk of mortality among HIV-infected subjects in a large healthcare system in the United States. AIDS Patient Care STDS. 2013 Aug;27(8):442-9. doi: 10.1089/apc.2013.0073. Epub 2013 Jul 19.

  PMID: 23869466 BACKGROUND

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; HIV Infections; Sexually Transmitted Diseases, Viral

Interventions

Darunavir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2020
• First Posted: May 14, 2020
• Study Start: September 1, 2021
• Primary Completion: April 5, 2024
• Study Completion: April 5, 2024
• Last Updated: April 26, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)