Monitoring SOF/VEL in Treatment Naïve, HCV Participants With Active Infection

NCT03512210 | Completed Phase 4 Results DMC FDA Drug

• 2 other identifiers: ACTG A5360UM1AI068636
• Study Type: interventional
• Target: 400
• Locations: 6 countries
• Sites: 38

Brief Summary

To achieve global hepatitis C virus (HCV) elimination by 2030, 80% of the \~71 million people with chronic HCV infection will need to be treated, necessitating simplification of treatment delivery and associated laboratory monitoring without compromising efficacy or safety. The COVID-19 pandemic has further highlighted the need for innovative models of health care delivery that minimize face-to-face patient-provider contact. The purpose of this study was to evaluate the feasibility, safety, and efficacy of a minimal monitoring (MINMON) strategy to deliver interferon- and RBV-free, pan-genotypic DAA therapy to treat active HCV in HCV treatment naïve participants.

Conditions

Hepatitis C; HIV-1-infection; Liver Diseases

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Sustained Virologic Response 12 (SVR12)

  SVR12 was defined as plasma HCV RNA less than the lower limit of quantification (LLOQ) from the earliest sample drawn at least 22 weeks following study treatment initiation (i.e. at a visit scheduled at least 10 weeks after scheduled end of study treatment). Participants without any HCV RNA result at least 22 weeks after treatment initiation will be considered as having HCV RNA greater than the LLOQ. LLOQ was defined as \<15 IU/mL for results tested at USA centralized testing laboratory Quest using the "Roche COBAS® HCV Quantitative nucleic acid test for use on the COBAS® 6800/8800" assays for quantitation (and detection) of HCV, and \<12 IU/mL for results tested at regional international labs using "Abbott RealTime HCV" assay for quantitation (and detection) of HCV. A two-sided 95%, confidence interval was calculated for this percentage using the Wilson (score) method.

  From at least 22 weeks and up to 76 weeks from treatment initiation

• Percentage of Participants With an Occurrence of Serious Adverse Events According to International Council for Harmonization (ICH) Criteria

  Serious adverse events (SAEs) as defined by ICH guidelines. A two-sided, 95% confidence interval was calculated for the percentage using the Wilson (score) method.

  From treatment initiation to 28 weeks

Secondary Outcomes (3)

• Percentage of Participants With at Least One Unplanned Clinic Visit Prior to SVR12 Evaluation

  From treatment initiation to 22 weeks

• Percentage of Participants With an Occurrence of One or More Non-serious, Grade >= 3 Adverse Event (AE), or Treatment Limiting AE.

  From treatment initiation to 28 weeks

• Percentage of Participants Who Prematurely Discontinued HCV Study Medications

  From at least 22 weeks and up to 76 weeks from treatment initiation

Study Arms (1)

MINMON 24 weeks with SOF/VEL 12 Weeks

EXPERIMENTAL

Participants received Sofosbuvir/Velpatasvir (SOF/VEL \[Tradename: Epclusa®\]) tablet for 12 weeks with a minimal monitoring (MINMON) strategy for 24 weeks

Drug: Sofosbuvir/Velpatasvir (SOF/VEL); Other: Minimal Monitoring (MINMON) Strategy

Interventions

Sofosbuvir/Velpatasvir (SOF/VEL) DRUG

400/100 mg fixed-dose combination (FDC) tablet administered orally once daily with or without food.

Also known as: Epclusa

MINMON 24 weeks with SOF/VEL 12 Weeks

Minimal Monitoring (MINMON) Strategy OTHER

MINMON Strategy: 1. No pre-treatment HCV genotyping 2. Entire treatment course (84) tablets of SOF/VEL administered to participants at study entry 3. No scheduled on-treatment laboratory monitoring or clinic visits 4. Remote contact with participants at week 4 and week 22

MINMON 24 weeks with SOF/VEL 12 Weeks

Eligibility Criteria

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

You may qualify if:

• Active Hepatitis C (HCV) infection, defined by HCV RNA \>1000 international units (IU/mL) within 35 days prior to study entry
• HCV treatment naïve
• Liver disease staged as either non-cirrhotic (Fibrosis-4 (FIB-4) Score \<3.25) or compensated cirrhotic (FIB-4 Score ≥3.25 and Child-Turcotte-Pugh (CTP) ≤Score 6) within 35 days prior to study entry
• HIV-1 negative, or HIV-1 positive with either a) Non-efavirenz containing antiretroviral therapy (ART) started at least 14 days prior to study entry with plasma HIV-1 RNA \<400 copies/mL within 90 days prior to study entry or b) not taking ART and CD4+ cell count \>350 cells/uL within 90 days prior to study entry
• The following laboratory values obtained within 35 days prior to study entry:
• Albumin \>3.0 g/L
• Hemoglobin \>8.0 g/dL for women; \>9.0 g/dL for men
• Platelet count \>50,000/mm\^3
• Calculated creatinine clearance (CrCl) \>30 mL/min
• Aspartate aminotransferase (AST) \<10 times the upper limit of the normal range (ULN)
• Alanine transaminase (ALT) \<10 times the ULN
• Total bilirubin \<1.5 times the ULN for participants not on atazanavir (ATV); \<3 times the ULN for participants on ATV
• International normalized ratio (INR) \<1.5 times the ULN
• For females of reproductive potential, a negative serum or urine pregnancy test within 48 hours prior to study entry
• All participants of reproductive potential must have agreed not to participate in conception process (e.g., active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization) while on study treatment and for 6 weeks after stopping study treatment

You may not qualify if:

• Positive for hepatitis B virus (HBV) surface antigen
• For cirrhotic participants, CTP score \>6 corresponding to Class B or C
• Breastfeeding or pregnancy
• Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulation
• Active drug or alcohol use or dependence and other conditions that, in the opinion of the site investigator, would interfere with adherence to study requirements.
• Acute or serious illness requiring systemic treatment and/or hospitalization within 35 days prior to study entry
• For HIV positive participants, presence of active or acute AIDS-defining opportunistic infections within 35 days prior to study entry
• Any history of hepatic decompensation including ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, hepatorenal syndrome, and/or bleeding esophageal varices
• Use of prohibited medications within the past 14 days prior to study entry

Sponsors & Collaborators

• Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (38)

Alabama CRS (31788)

Birmingham, Alabama, 35294, United States

Location

University of Southern California (1201)

Los Angeles, California, 90033-1079, United States

Location

UCLA CARE Center CRS (601)

Los Angeles, California, 90095, United States

Location

Ucsd, Avrc Crs (701)

San Diego, California, 92103, United States

Location

Ucsf Aids Crs (801)

San Francisco, California, 94110, United States

Location

University of Colorado Hospital CRS (6101)

Aurora, Colorado, 80045, United States

Location

Whitman Walker Health CRS (31791)

Washington D.C., District of Columbia, 20009, United States

Location

The Ponce de Leon Center CRS (5802)

Atlanta, Georgia, 30308, United States

Location

Northwestern University CRS (2701)

Chicago, Illinois, 60611, United States

Location

Rush Univ. Med. Ctr. ACTG CRS (2702)

Chicago, Illinois, 60612, United States

Location

Johns Hopkins University CRS (201)

Baltimore, Maryland, 21205, United States

Location

Massachusetts General Hospital (MGH) CRS (101)

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hosp. ACTG CRS (107)

Boston, Massachusetts, 02115, United States

Location

Washington U CRS (2101)

St Louis, Missouri, 63110, United States

Location

New Jersey Medical School Clinical Research Center CRS (31786)

Newark, New Jersey, 07103, United States

Location

Weill Cornell Chelsea CRS (7804)

New York, New York, 10010, United States

Location

Columbia Physicians and Surgeons CRS (30329)

New York, New York, 10032, United States

Location

Weill Cornell Upton CRS (7803)

New York, New York, 10065, United States

Location

University of Rochester Adult HIV Therapeutic Strategies Network CRS (31787)

Rochester, New York, 14642, United States

Location

Unc Aids Crs (3201)

Chapel Hill, North Carolina, 27514, United States

Location

Greensboro CRS (3203)

Greensboro, North Carolina, 27401, United States

Location

Univ. of Cincinnati CRS (2401)

Cincinnati, Ohio, 45267, United States

Location

Case CRS (2501)

Cleveland, Ohio, 44106, United States

Location

The Ohio State Univ. AIDS CRS (2301)

Columbus, Ohio, 43210, United States

Location

Hosp. of the Univ. of Pennsylvania CRS (6201)

Philadelphia, Pennsylvania, 19104, United States

Location

Pittsburgh CRS (1001)

Pittsburgh, Pennsylvania, 15213, United States

Location

The Miriam Hospital ACTG CRS (2951)

Providence, Rhode Island, 02906, United States

Location

Vanderbilt Therapeutics (VT) CRS (3652)

Nashville, Tennessee, 37204, United States

Location

Trinity Health and Wellness Center CRS (31443)

Dallas, Texas, 75208, United States

Location

Houston AIDS Research Team CRS (31473)

Houston, Texas, 77030, United States

Location

Hospital Nossa Senhora da Conceicao CRS (12201)

Porto Alegre, Rio Grande do Sul, 9043010, Brazil

Location

Instituto de Pesquisa Clinica Evandro Chagas (12101)

Rio de Janeiro, 21045, Brazil

Location

Puerto Rico-AIDS CRS (5401)

San Juan, 00931, Puerto Rico

Location

University of the Witwatersrand Helen Joseph (WITS HJH) CRS (11101)

Johannesburg, Gauteng, 2193, South Africa

Location

Family Clinical Research Unit (FAM-CUR) CRS (8950)

Cape Town, West Cape, 7505, South Africa

Location

Thai Red Cross AIDS Research Centre (TRC-ARC) CRS (31802)

Bangkok, Patumwan, 10330, Thailand

Location

Chiang Mai University HIV Treatment CRS (31784)

Chiang Mai, 50200, Thailand

Location

Joint Clinical Research Centre (JCRC) (12401)

Kampala, Uganda

Location

Related Publications (4)

• Torres TS, Saha PT, Smeaton L, Wimbish C, Kliemann DA, Avihingsanon A, Kityo C, Bennet JA, Van Schalkwyk M, Linas B, Nunes EP, Robbins GK, Wyles D, Naggie S, Sulkowski M, Cardoso SW, Solomon S. Impact of a minimal monitoring HCV treatment approach on Health-Related Quality of Life. Qual Life Res. 2025 Jun;34(6):1683-1694. doi: 10.1007/s11136-025-03922-1. Epub 2025 Feb 28.

  PMID: 40019678 DERIVED

• Han WM, Solomon SS, Smeaton L, Avihingsanon A, Wagner Cardoso S, Li J, Parvangada A, Sulkowski M, Naggie S, Martin R, Mo H, Maiorova E, Wyles D. Reinfection and Resistance Associated Substitutions Following a Minimal Monitoring Approach for Hepatitis C Virus Treatment in MINMON Trial. Clin Infect Dis. 2025 Jul 18;80(6):1293-1301. doi: 10.1093/cid/ciae627.

  PMID: 39702964 DERIVED

• Sowah LA, Smeaton L, Brates I, Bhattacharya D, Linas B, Kreter B, Wagner-Cardoso S, Solomon S, Sulkowski M, Robbins GK. Perspectives on Adherence From the ACTG 5360 MINMON Trial: A Minimum Monitoring Approach With 12 Weeks of Sofosbuvir/Velpatasvir in Chronic Hepatitis C Treatment. Clin Infect Dis. 2023 Jun 8;76(11):1959-1968. doi: 10.1093/cid/ciad034.

  PMID: 36694361 DERIVED

• Solomon SS, Wagner-Cardoso S, Smeaton L, Sowah LA, Wimbish C, Robbins G, Brates I, Scello C, Son A, Avihingsanon A, Linas B, Anthony D, Nunes EP, Kliemann DA, Supparatpinyo K, Kityo C, Tebas P, Bennet JA, Santana-Bagur J, Benson CA, Van Schalkwyk M, Cheinquer N, Naggie S, Wyles D, Sulkowski M. A minimal monitoring approach for the treatment of hepatitis C virus infection (ACTG A5360 [MINMON]): a phase 4, open-label, single-arm trial. Lancet Gastroenterol Hepatol. 2022 Apr;7(4):307-317. doi: 10.1016/S2468-1253(21)00397-6. Epub 2022 Jan 10.

  PMID: 35026142 DERIVED

Related Links

• DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1
• Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010
• NIH. BLAST® Basic Local Alignment Search Tool. US National Library of Medicine, National Center for Biotechnology Information, NIH; 2021

MeSH Terms

Conditions

Hepatitis C; Liver Diseases

Interventions

Sofosbuvir; velpatasvir; sofosbuvir-velpatasvir drug combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Uridine Monophosphate; Uracil Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides

Results Point of Contact

• Title: ACTG Clinicaltrials.gov Coordinator
• Organization: ACTG Network Coordinating Center, Social and Scientific Systems, a DLH Holdings Company

ACTGCT.gov@fstrf.org

301-628-3348

Study Officials

• Sunil Solomon, MBBS, PhD, MPH

  Johns Hopkins University

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: April 19, 2018
• First Posted: April 30, 2018
• Study Start: October 22, 2018
• Primary Completion: July 30, 2020
• Study Completion: February 28, 2021
• Last Updated: February 4, 2022
• Results First Posted: July 16, 2021

Record last verified: 2022-01

Locations

BR (2); ZA (2); US (30); TH (2); UG (1); PR (1)