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

NCT ID: NCT03512210

Last Updated: 2022-02-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 400 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-22
• Study Completion Date: 2021-02-28

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.

Detailed Description

This study evaluated the feasibility, safety, and efficacy of a minimal monitoring (MINMON) strategy of delivering interferon- and ribavirin (RBV)-free, pan-genotypic direct-acting antiviral (DAA) therapy to treat active hepatitis C virus (HCV) in HCV treatment naïve participants, with or without HIV-1 co-infection, and with no evidence of decompensated cirrhosis.

The MINMON intervention included four components: 1) No pre-treatment HCV genotyping; 2) Entire 12-week treatment course (84 tablets) dispensed to participants at study entry; 3) No scheduled on-treatment laboratory monitoring or clinic visits prior to SVR evaluation scheduled 24 weeks following entry; 4) Remote contact with participants at week 4 for adherence counseling and locator update, and week 22 for scheduling of SVR visit and locator update.

At study entry, all participants received a single-tablet, fixed-dose combination (FDC) of sofosbuvir/velpatasvir (SOF/VEL) for 12 weeks.

The trial was designed to accrue 400 adult participants who may be co-infected with HIV-1 (limited to no more than 200 participants), and whose liver disease state is either no cirrhosis (defined by Fibrosis-4 score) or compensated cirrhosis (defined by Fibrosis-4 and Child-Turcotte-Pugh (CTP) scores, and limited to no more than 80 participants). Accrual from research sites in the United States was limited to no more than 132 participants.

The study proceeded in two steps: Step 1: MINMON intervention and Step 2: post-MINMON follow up.

During Step 1 (MINMON intervention), participants were contacted remotely at week 4 to inquire about study medication adherence and confirm locator information, and again at week 22 to schedule the sustained virologic response (SVR) evaluation and confirm locator information. Unplanned in-person clinic visits before week 22 were permissible to address common treatment toxicities that could not be managed remotely. The primary efficacy outcome measure, sustained virologic response (SVR), was evaluated starting at the week 24 study visit. Early discontinuation of treatment did not alter the timing of the SVR evaluation. If the week 24 visit was missed, SVR could be evaluated at any time up to 76 weeks following study entry.

Following SVR evaluation, participants entered Step 2 for two additional post-SVR evaluation study visits at weeks 48 and 72. Participants were contacted remotely at weeks 42 and 68 to schedule such visits. The schedule of additional post-MINMON evaluation visits were dependent on the week of Step 2 entry.

In version 1 of the study, total study duration was up to 76 weeks. Due to the COVID-19 Pandemic, the window of the week 72 visit was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites. This extension did not alter the window for SVR evaluation.

All scheduled in-clinic study visits included a physical exam, blood collection, and collection of plasma samples. For participants able to become pregnant, pregnancy testing was conducted at screening, entry, and at any in-clinic visit during Step 1 if pregnancy was suspected. Liver Elastography was an optional evaluation.

Conditions

Hepatitis C; HIV-1-infection; Liver Diseases

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MINMON 24 weeks with SOF/VEL 12 Weeks

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

Group Type: EXPERIMENTAL

Sofosbuvir/Velpatasvir (SOF/VEL)

Intervention Type: DRUG

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

Minimal Monitoring (MINMON) Strategy

Intervention Type: 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

Interventions

Sofosbuvir/Velpatasvir (SOF/VEL)

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

Intervention Type: DRUG

Minimal Monitoring (MINMON) Strategy

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

Intervention Type: OTHER

Other Intervention Names

Epclusa

Eligibility Criteria

Inclusion Criteria

• 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
• If participating in sexual activity that could lead to pregnancy, the all participants of reproductive potential had to agree to use at least one reliable methods of contraception while on study treatment and for 6 weeks after stopping study treatment
• Participants who were not of reproductive potential were eligible without requiring the use of contraceptives.
• Life expectancy >12 months
• Ability and willingness to be contacted remotely
• Ability and willingness of participant to provide informed consent.

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sunil Solomon, MBBS, PhD, MPH

Role: STUDY_CHAIR

Johns Hopkins University

Locations

Alabama CRS (31788)

Birmingham, Alabama, United States

University of Southern California (1201)

Los Angeles, California, United States

UCLA CARE Center CRS (601)

Los Angeles, California, United States

Ucsd, Avrc Crs (701)

San Diego, California, United States

Ucsf Aids Crs (801)

San Francisco, California, United States

University of Colorado Hospital CRS (6101)

Aurora, Colorado, United States

Whitman Walker Health CRS (31791)

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

The Ponce de Leon Center CRS (5802)

Atlanta, Georgia, United States

Northwestern University CRS (2701)

Chicago, Illinois, United States

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

Chicago, Illinois, United States

Johns Hopkins University CRS (201)

Baltimore, Maryland, United States

Massachusetts General Hospital (MGH) CRS (101)

Boston, Massachusetts, United States

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

Boston, Massachusetts, United States

Washington U CRS (2101)

St Louis, Missouri, United States

New Jersey Medical School Clinical Research Center CRS (31786)

Newark, New Jersey, United States

Weill Cornell Chelsea CRS (7804)

New York, New York, United States

Columbia Physicians and Surgeons CRS (30329)

New York, New York, United States

Weill Cornell Upton CRS (7803)

New York, New York, United States

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

Rochester, New York, United States

Unc Aids Crs (3201)

Chapel Hill, North Carolina, United States

Greensboro CRS (3203)

Greensboro, North Carolina, United States

Univ. of Cincinnati CRS (2401)

Cincinnati, Ohio, United States

Case CRS (2501)

Cleveland, Ohio, United States

The Ohio State Univ. AIDS CRS (2301)

Columbus, Ohio, United States

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

Philadelphia, Pennsylvania, United States

Pittsburgh CRS (1001)

Pittsburgh, Pennsylvania, United States

The Miriam Hospital ACTG CRS (2951)

Providence, Rhode Island, United States

Vanderbilt Therapeutics (VT) CRS (3652)

Nashville, Tennessee, United States

Trinity Health and Wellness Center CRS (31443)

Dallas, Texas, United States

Houston AIDS Research Team CRS (31473)

Houston, Texas, United States

Hospital Nossa Senhora da Conceicao CRS (12201)

Porto Alegre, Rio Grande do Sul, Brazil

Instituto de Pesquisa Clinica Evandro Chagas (12101)

Rio de Janeiro, , Brazil

Puerto Rico-AIDS CRS (5401)

San Juan, , Puerto Rico

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

Johannesburg, Gauteng, South Africa

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

Cape Town, West Cape, South Africa

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

Bangkok, Patumwan, Thailand

Chiang Mai University HIV Treatment CRS (31784)

Chiang Mai, , Thailand

Joint Clinical Research Centre (JCRC) (12401)

Kampala, , Uganda

Countries

United States; Brazil; Puerto Rico; South Africa; Thailand; Uganda

References

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.

Reference Type: DERIVED

PMID: 40019678 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 39702964 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36694361 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35026142 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Related Links

http://rsc.niaid.nih.gov/clinical-research-sites/daids-adverse-event-grading-tables

DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1

http://rsc.niaid.nih.gov/clinical-research-sites/manual-expedited-reporting-adverse-events-daids

Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010

http://blast.ncbi.nlm.nih.gov/Blast.cgi

NIH. BLAST® Basic Local Alignment Search Tool. US National Library of Medicine, National Center for Biotechnology Information, NIH; 2021

Other Identifiers

UM1AI068636

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ACTG A5360

Identifier Type: -

Identifier Source: org_study_id