What Is Glecaprevir/pibrentasvir?
Glecaprevir/pibrentasvir is an FDA-approved medication for the treatment of chronic Hepatitis C viral infection across various genotypes, including in patients without cirrhosis or with compensated cirrhosis, and in those previously treated with certain HCV inhibitors. This medication is a combination of two direct-acting antiviral drugs. Glecaprevir acts as an NS3/4A protease inhibitor, while pibrentasvir functions as an NS5A inhibitor. These components target specific viral proteins that are essential for the Hepatitis C virus to replicate.
While approved for chronic Hepatitis C, glecaprevir/pibrentasvir is also being investigated for use in adult and adolescent participants with acute HCV infection. Studies are also exploring its potential to treat Hepatitis C infection in recipients of organs from Hepatitis C positive donors, which could help expand the pool of available organs for transplantation.
Uses and Conditions Under Study
Glecaprevir/pibrentasvir is primarily studied for the treatment of Hepatitis C viral infection. Hepatitis C is a global health problem where the virus mainly affects liver cells, causing inflammation and damage. As a direct-acting antiviral, glecaprevir/pibrentasvir targets the virus to prevent its replication and clear the infection. A total of 35 trials are investigating glecaprevir/pibrentasvir for various forms of Hepatitis C, including acute and chronic infections, and across different genotypes. Some studies, such as NCT03316654, are also exploring its use in patients who receive organs from Hepatitis C positive donors, to treat the resulting infection and expand the pool of available organs for transplantation.
The medication is also being investigated in patients with kidney-related conditions. End Stage Renal Disease (ESRD) and Kidney Failure are severe kidney conditions. Four trials are studying glecaprevir/pibrentasvir in this population, likely to assess its safety and effectiveness in individuals whose kidney function may affect drug metabolism or who have co-existing Hepatitis C infection. For example, NCT03316654 involves HCV-positive kidney transplant recipients.
Additionally, glecaprevir/pibrentasvir is being studied in two trials related to Post-Traumatic Stress Disorder (PTSD). While not directly treating PTSD, these studies may examine the drug's use in populations where HCV infection and PTSD are common comorbidities, such as certain veteran populations or individuals with a history of substance use, to ensure comprehensive care.
Dosing
Glecaprevir/pibrentasvir is typically administered as oral tablets. The standard adult dose studied in trials consists of 100 mg glecaprevir and 40 mg pibrentasvir per tablet. Patients usually take three of these tablets orally once daily, resulting in a total daily dose of 300 mg glecaprevir and 120 mg pibrentasvir.
Treatment durations commonly studied include 8 weeks or 12 weeks, depending on the specific patient population and their Hepatitis C genotype and prior treatment history. Some investigational regimens also explore durations of 4 or 16 weeks, and combinations with other antiviral medications like sofosbuvir (SOF) and ribavirin (RBV).
In addition to adult dosing, glecaprevir/pibrentasvir is being investigated for pediatric use. Studies are exploring both adult and pediatric formulations for different age groups, including:
- Children 12 to less than 18 years
- Children 9 to less than 12 years
- Children 6 to less than 9 years
- Children 3 to less than 6 years
These studies aim to determine appropriate and safe dosing for younger patients with Hepatitis C infection.
Side Effects
In clinical trials, the most commonly reported side effect for Glecaprevir/pibrentasvir was upper respiratory tract infection. In one study involving 544 patients, 10.7% of patients taking Glecaprevir/pibrentasvir experienced an upper respiratory tract infection, compared to 9.8% of patients taking a placebo.
Information on other common side effects with placebo comparisons was not provided in this dataset.
Clinical Trial Results
Treatment in Post-Liver or Post-Renal Transplant Recipients
A study (NCT02692703) evaluated Glecaprevir/pibrentasvir in adult patients who had received a liver or kidney transplant and had chronic hepatitis C virus (HCV). In this trial, 98% of participants achieved a sustained virologic response 12 weeks after treatment (SVR12), meaning the virus was undetectable. No participants experienced virologic failure during treatment, and only 1% experienced a relapse after treatment.
Treatment in Patients Who Did Not Respond to Previous HCV Therapy
Another study (NCT02939989) investigated Glecaprevir/pibrentasvir in combination with sofosbuvir and ribavirin for patients with HCV who had not responded to prior AbbVie clinical studies. Overall, 97.0% of these difficult-to-treat patients achieved SVR12. No participants experienced virologic failure during treatment, and 3.0% experienced a relapse after treatment. For those treated for 12 weeks, 100% achieved SVR12, while for those treated for 16 weeks, 96.4% achieved SVR12.
Treatment for Hepatitis C Virus Genotype 5 or 6
In a study (NCT02966795) focusing on adults with chronic HCV Genotype 5 or 6 infection, high rates of viral clearance were observed. Among patients with Genotype 5, 95.7% achieved SVR12. For those with Genotype 6, 98.4% achieved SVR12. On-treatment virologic failure occurred in 0.0% of Genotype 5 patients and 1.6% of Genotype 6 patients. Relapse occurred in 4.3% of Genotype 5 patients, but in 0.0% of Genotype 6 patients.
Treatment in Pediatric Patients with Chronic Hepatitis C Virus
A study (NCT03067129) evaluated Glecaprevir/pibrentasvir in pediatric patients aged 3 to less than 18 years with chronic HCV Genotypes 1-6. Overall, 97.6% of pediatric participants achieved SVR12. No participants experienced virologic failure during treatment, and 0.8% experienced a relapse after treatment. SVR12 rates varied slightly by age group: 100% for those 12 to less than 18 years, 93.1% for those 9 to less than 12 years, 100% for those 6 to less than 9 years, and 95.8% for those 3 to less than 6 years.
Regarding the ease of taking the medicine, caregivers reported mixed experiences for pediatric patients aged 3 to less than 12 years. While most doses were administered quickly (less than 1 minute for 66 participants) and successfully (58 participants), the convenience of preparing the dose was often rated as inconvenient or very inconvenient by 44 participants. Additionally, swallowing the medicine was rated as difficult or very difficult by 40 participants, while 29 participants found it very easy.
Treatment in Adults with Chronic Hepatitis C Virus and Renal Impairment
A study (NCT03069365) assessed Glecaprevir/pibrentasvir in adults with chronic HCV Genotype 1-6 infection and renal impairment. In this population, 97.0% of participants achieved SVR12. No participants experienced on-treatment virologic failure or post-treatment relapse.
Currently Recruiting Trials
Several clinical trials are actively recruiting participants to further investigate glecaprevir/pibrentasvir. These studies aim to expand our understanding of the drug's effects across different conditions and patient populations. The National Institute of Allergy and Infectious Diseases is sponsoring a Phase I/II study, NCT07040319, investigating glecaprevir/pibrentasvir. This multi-site, open-label trial aims to understand how the drug is processed in the body (pharmacokinetics) and its safety when initiated during pregnancy in women with hepatitis C virus (HCV) infection, including those also living with HIV. The study will also evaluate the safety for their infants. The trial plans to enroll 30 participants. Another study, NCT06367465, led by Washington University School of Medicine, focuses on the practical aspects and acceptance of hepatitis C treatment during pregnancy. This trial seeks to enroll 50 pregnant adults over 18 years old who have hepatitis C virus infection and a history of past or current drug use. Participants are expected to be involved for approximately 1 year. The White River Junction Veterans Affairs Medical Center is conducting a Phase II/III double-blind, randomized, placebo-controlled trial, NCT05637879, exploring glecaprevir/pibrentasvir for Post-traumatic Stress Disorder (PTSD). This study will further investigate the drug's potential to improve PTSD symptoms, an effect observed when it was prescribed for chronic hepatitis C viral infection. The trial is recruiting 92 participants.Where to Participate
Clinical trials for glecaprevir/pibrentasvir are currently active across 9 states, with a total of 13 sites in 10 cities. The top locations where you might find a study site include:- Los Angeles, California (2 sites)
- St Louis, Missouri (2 sites)
- The Bronx, New York (2 sites)
- Chicago, Illinois
- Baltimore, Maryland
- Houston, Texas
- Stony Brook, New York
- White River Junction, Vermont
- Aurora, Colorado
- Jacksonville, Florida