What Is Glecaprevir/pibrentasvir?
Glecaprevir/pibrentasvir is an FDA-approved medication for the treatment of hepatitis C viral infection. This medication is a direct-acting antiviral that combines two different drugs: glecaprevir and pibrentasvir. Glecaprevir works by inhibiting the NS3/4A protease, while pibrentasvir inhibits the NS5A protein. By targeting these specific viral proteins, the medication prevents the hepatitis C virus from replicating and spreading in the body.
It is approved for treating chronic hepatitis C virus (HCV) infection across genotypes 1, 2, 3, 4, 5, or 6 in patients without cirrhosis or with compensated cirrhosis. It is also approved for adult patients with HCV genotype 1 infection who have previously been treated with certain other HCV medications. Beyond its approved uses, glecaprevir/pibrentasvir is being investigated in clinical trials for acute HCV infection in adults and adolescents, as well as for treating HCV in patients undergoing or who have received organ transplantation, particularly kidney transplants. These studies aim to evaluate its safety and effectiveness in these specific populations.
Uses and Conditions Under Study
Glecaprevir/pibrentasvir is primarily studied for its effectiveness in treating various forms of hepatitis C. This includes Hepatitis C (18 trials), Hepatitis C Virus (HCV) (9 trials), HCV (3 trials), Chronic Hepatitis c (2 trials), Hepatitis C Virus Infection (2 trials), Hepatitis C Infection (1 trial), and Hepatitis C Virus (1 trial). In total, 36 trials investigate this medication for HCV-related conditions. Hepatitis C is a viral infection that causes inflammation and damage to the liver. As a direct-acting antiviral, glecaprevir/pibrentasvir is designed to target and eliminate the virus, offering a cure for many patients.
The medication is also being investigated for its use in patients with kidney-related conditions, specifically End Stage Renal Disease (3 trials) and Kidney Failure (2 trials). These conditions often coexist with or are complicated by HCV infection. Studies are exploring the possibility of using organs from HCV-positive donors for transplantation and then treating the recipient with glecaprevir/pibrentasvir to clear the infection. This could expand the pool of available donor organs and improve transplant outcomes for patients with kidney failure.
Additionally, glecaprevir/pibrentasvir is being studied in 2 trials for PTSD (Post-Traumatic Stress Disorder). While the direct connection between PTSD and an antiviral for hepatitis C is not immediately apparent from the provided data, these trials may be exploring broader health outcomes or specific patient populations where both conditions are prevalent, or investigating potential indirect effects of HCV treatment on mental health.
Dosing
Glecaprevir/pibrentasvir is available as oral tablets. The standard adult daily dose studied in many trials is 300 mg glecaprevir and 120 mg pibrentasvir, taken once daily. This is typically administered as three 100 mg glecaprevir/40 mg pibrentasvir tablets taken together. Treatment durations have varied in studies, including regimens of 8 weeks, 12 weeks, or 16 weeks, and sometimes for 56 days, depending on the patient's specific condition and prior treatment history.
Clinical trials have explored different dosing strategies and combinations. Some studies have investigated glecaprevir/pibrentasvir alone for 8 or 12 weeks, while others have combined it with other antivirals like sofosbuvir (SOF) and ribavirin (RBV) for durations of 12 or 16 weeks. For example, one study arm involved G/P 300 mg/120 mg once daily for 12 weeks, while another explored the same dose for 16 weeks, sometimes with added RBV.
Pediatric formulations and dosing are also under investigation for various age groups. Studies are evaluating glecaprevir/pibrentasvir in children aged 3 to less than 6 years, 6 to less than 9 years, 9 to less than 12 years, and 12 to less than 18 years. These trials aim to determine appropriate and safe pediatric doses and formulations, including both adult and specific pediatric formulations, to treat HCV infection in younger patients.
Side Effects
In clinical trials, the most common side effect reported for Glecaprevir/pibrentasvir was upper respiratory tract infection. In one trial involving 544 patients receiving the drug, 10.7% experienced an upper respiratory tract infection, compared to 9.8% of patients who received a placebo.
Only limited adverse event data with placebo comparison was provided for Glecaprevir/pibrentasvir.
Clinical Trial Results
Clinical trials have shown that Glecaprevir/pibrentasvir is highly effective in treating chronic Hepatitis C Virus (HCV) across various patient populations, including those who have undergone transplants, previously failed treatment, or have specific HCV genotypes.
For Post-Liver or Post-Renal Transplant Recipients
In a study (NCT02692703) of adult post-liver or post-renal transplant recipients with chronic HCV, Glecaprevir/pibrentasvir demonstrated high efficacy. 98% of participants achieved a sustained virologic response 12 weeks post-treatment (SVR12), meaning the virus was undetectable. No participants experienced virologic failure during treatment, and only 1% experienced a relapse after treatment.
For Patients Who Previously Failed Treatment
A study (NCT02939989) evaluated Glecaprevir/pibrentasvir in combination with sofosbuvir and ribavirin for participants who had not responded to previous HCV treatments. Overall, 97.0% of these treatment-experienced patients achieved SVR12. No participants experienced virologic failure during treatment, and 3.0% experienced a relapse after treatment.
For Patients with HCV Genotype 5 or 6
In a trial (NCT02966795) focusing on adults with chronic HCV Genotype 5 or 6 infection, Glecaprevir/pibrentasvir showed strong results. For those with Genotype 5, 95.7% achieved SVR12, with no on-treatment virologic failure. For those with Genotype 6, 98.4% achieved SVR12, with only 1.6% experiencing on-treatment virologic failure. Relapse rates were 4.3% for Genotype 5 and 0.0% for Genotype 6.
For Pediatric Patients
A study (NCT03067129) in pediatric subjects aged 3 to less than 18 years with chronic HCV Genotypes 1-6 showed an overall SVR12 rate of 97.6%. No pediatric participants experienced on-treatment virologic failure, and the overall post-treatment relapse rate was 0.8%.
For Patients with Renal Impairment
In a study (NCT03069365) of adults with chronic HCV Genotype 1-6 infection and renal impairment, Glecaprevir/pibrentasvir achieved an SVR12 rate of 97.0%. No participants in this group experienced on-treatment virologic failure or post-treatment relapse.
Currently Recruiting Trials
Glecaprevir/pibrentasvir is currently being investigated in several clinical trials, exploring its potential benefits for patients with hepatitis C and other conditions. These studies aim to gather more information about the drug's safety and effectiveness in different populations.
One ongoing study, NCT07040319, is a Phase I/II trial sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). This study is examining the pharmacokinetics (how the body processes the drug) and safety of glecaprevir/pibrentasvir when initiated during pregnancy. It enrolls pregnant women with acute or chronic hepatitis C virus infection, with or without HIV, and also evaluates the safety for their infants. The trial aims to enroll 30 participants.
Another trial, NCT06367465, is exploring the feasibility and acceptability of hepatitis C treatment during pregnancy. Sponsored by Washington University School of Medicine, this study focuses on pregnant adults over the age of 18 who have hepatitis C virus infection and a history of past or current drug use. Participants are recruited from Washington University obstetrics and gynecology, maternal fetal medicine, or infectious diseases clinics, or if admitted to Barnes-Jewish Hospital. The study plans to enroll 50 participants, with individual participation lasting approximately 1 year.
Beyond hepatitis C, glecaprevir/pibrentasvir is also being studied for its potential role in treating post-traumatic stress disorder (PTSD). The White River Junction Veterans Affairs Medical Center is sponsoring a Phase II/III, double-blind, randomized, placebo-controlled trial, NCT05637879. This study aims to further investigate glecaprevir/pibrentasvir for PTSD symptom improvement, building on observations where the drug was associated with such improvements when prescribed for chronic hepatitis C viral infection. This trial targets an enrollment of 92 participants.
Where to Participate
Clinical trials for glecaprevir/pibrentasvir are being conducted across a broad geographic area, offering opportunities for participation in various locations. Currently, studies are active at 13 sites across 10 cities in 9 states.
Top locations with multiple sites include:
- Los Angeles, California (2 sites)
- St Louis, Missouri (2 sites)
- The Bronx, New York (2 sites)
Other cities hosting trials include Chicago, Illinois; Baltimore, Maryland; Houston, Texas; Stony Brook, New York; White River Junction, Vermont; Aurora, Colorado; and Jacksonville, Florida.
Eligibility criteria for these trials generally include individuals aged 16 to 70 years, with participation open to all genders. Healthy volunteers are not being recruited for these specific studies, as they focus on individuals with particular medical conditions or circumstances, such as hepatitis C, pregnancy, or PTSD. Children are eligible for some studies, depending on the specific trial's age requirements.
Development Timeline
The journey of glecaprevir/pibrentasvir in clinical research began on December 17, 2015, marking the start of its first clinical trial. Since then, the drug has been the subject of 40 clinical trials, enrolling a total of 5,239 participants. The latest trial is projected to conclude on June 27, 2025.
Initial investigations for glecaprevir/pibrentasvir focused on conditions like Irritable Bowel Syndrome with Constipation (IBS-C) and hyperphosphatemia. Over time, the research pipeline significantly expanded, with studies exploring its efficacy for a diverse range of conditions. Key areas of expansion included End Stage Renal Disease, various forms of Hepatitis C (HCV, Chronic Hepatitis C, Acute Hepatitis C, Hepatitis C Virus Infection), and even Post-traumatic Stress Disorder (PTSD).
AbbVie has been a primary driver of this development, sponsoring 12 trials. Other notable sponsors include the Kirby Institute, White River Junction Veterans Affairs Medical Center, and Johns Hopkins University, among others. The drug has progressed through various stages of clinical development, with 14 trials reaching Phase III, 10 trials in Phase IV, and others in earlier phases, including Phase I/II and Phase II/III studies. This progression highlights a comprehensive effort to understand the full therapeutic potential of glecaprevir/pibrentasvir across a broad spectrum of diseases.