Clinical trial NCT03512210: Monitoring SOF/VEL in Treatment Naïve, HCV Participants With Active Infection
Official title: A Single-arm Study to Evaluate the Feasibility and Efficacy of a Minimal Monitoring Strategy to Deliver Pan-genotypic Ribavirin-free HCV Therapy to HCV Infected Populations Who Are HCV Treatment Naïve With Evidence of Active HCV Infection: The MINMON Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hepatitis C
HIV-1-infection
Liver Diseases
Lead sponsor: Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
Sponsor class: NETWORK
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2018-04-30
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Percentage of Participants With Sustained Virologic Response 12 (SVR12)
timeFrame: From at least 22 weeks and up to 76 weeks from treatment initiation
measure: Percentage of Participants With an Occurrence of Serious Adverse Events According to International Council for Harmonization (ICH) Criteria
timeFrame: From treatment initiation to 28 weeks
Secondary outcomes:
measure: Percentage of Participants With at Least One Unplanned Clinic Visit Prior to SVR12 Evaluation
timeFrame: From treatment initiation to 22 weeks
measure: Percentage of Participants With an Occurrence of One or More Non-serious, Grade >= 3 Adverse Event (AE), or Treatment Limiting AE.
timeFrame: From treatment initiation to 28 weeks
measure: Percentage of Participants Who Prematurely Discontinued HCV Study Medications
timeFrame: From at least 22 weeks and up to 76 weeks from treatment initiation
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama CRS (31788)
state: Alabama
city: Los Angeles
country: United States
facility: University of Southern California (1201)
state: California
city: Los Angeles
country: United States
facility: UCLA CARE Center CRS (601)
state: California
city: San Diego
country: United States
facility: Ucsd, Avrc Crs (701)
state: California
city: San Francisco
country: United States
facility: Ucsf Aids Crs (801)
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital CRS (6101)
state: Colorado
city: Washington
country: United States
facility: Whitman Walker Health CRS (31791)
state: District of Columbia
city: Atlanta
country: United States
facility: The Ponce de Leon Center CRS (5802)
state: Georgia
city: Chicago
country: United States
facility: Northwestern University CRS (2701)
state: Illinois
city: Chicago
country: United States
facility: Rush Univ. Med. Ctr. ACTG CRS (2702)
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins University CRS (201)
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital (MGH) CRS (101)
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hosp. ACTG CRS (107)
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington U CRS (2101)
state: Missouri
city: Newark
country: United States
facility: New Jersey Medical School Clinical Research Center CRS (31786)
state: New Jersey
city: New York
country: United States
facility: Weill Cornell Chelsea CRS (7804)
state: New York
city: New York
country: United States
facility: Columbia Physicians and Surgeons CRS (30329)
state: New York
city: New York
country: United States
facility: Weill Cornell Upton CRS (7803)
state: New York
city: Rochester
country: United States
facility: University of Rochester Adult HIV Therapeutic Strategies Network CRS (31787)
state: New York
city: Chapel Hill
country: United States
facility: Unc Aids Crs (3201)
state: North Carolina
city: Greensboro
country: United States
facility: Greensboro CRS (3203)
state: North Carolina
city: Cincinnati
country: United States
facility: Univ. of Cincinnati CRS (2401)
state: Ohio
city: Cleveland
country: United States
facility: Case CRS (2501)
state: Ohio
city: Columbus
country: United States
facility: The Ohio State Univ. AIDS CRS (2301)
state: Ohio
city: Philadelphia
country: United States
facility: Hosp. of the Univ. of Pennsylvania CRS (6201)
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Pittsburgh CRS (1001)
state: Pennsylvania
city: Providence
country: United States
facility: The Miriam Hospital ACTG CRS (2951)
state: Rhode Island
city: Nashville
country: United States
facility: Vanderbilt Therapeutics (VT) CRS (3652)
state: Tennessee
city: Dallas
country: United States
facility: Trinity Health and Wellness Center CRS (31443)
state: Texas
city: Houston
country: United States
facility: Houston AIDS Research Team CRS (31473)
state: Texas
city: Porto Alegre
country: Brazil
facility: Hospital Nossa Senhora da Conceicao CRS (12201)
state: RS
city: Rio de Janeiro
country: Brazil
facility: Instituto de Pesquisa Clinica Evandro Chagas (12101)
city: San Juan
country: Puerto Rico
facility: Puerto Rico-AIDS CRS (5401)
city: Johannesburg
country: South Africa
facility: University of the Witwatersrand Helen Joseph (WITS HJH) CRS (11101)
state: Gauteng
city: Cape Town
country: South Africa
facility: Family Clinical Research Unit (FAM-CUR) CRS (8950)
state: West Cape
city: Bangkok
country: Thailand
facility: Thai Red Cross AIDS Research Centre (TRC-ARC) CRS (31802)
state: Patumwan
city: Chiang Mai
country: Thailand
facility: Chiang Mai University HIV Treatment CRS (31784)
city: Kampala
country: Uganda
facility: Joint Clinical Research Centre (JCRC) (12401)
Study officials:
affiliation: Johns Hopkins University
name: Sunil Solomon, MBBS, PhD, MPH
role: STUDY_CHAIR
References:
citation: 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.