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Chronic hepatitis C patients with HIV-1 co-infection and liver transplant recipients: treatment with Ombitasvir, ABT-450 / Ritonavir and Dasabuvir

Results from studies in chronic hepatitis C patients with human immunodeficiency virus type 1 ( HIV-1 ) co-infection ( TURQUOISE-I ) and liver transplant recipients ( CORAL-I ) were presented at The Liver Meeting 2014.

New, detailed results from part one of the Phase 2 portion of a phase 2/3 open-label study, TURQUOISE-I, showed patients co-infected with genotype 1 ( GT1 ) hepatitis C virus ( HCV ) and HIV-1 receiving an investigational treatment and Ribavirin ( RBV ) for 12 weeks or 24 weeks achieved sustained virologic response rates 12 weeks post-treatment ( SVR12 ) of 93.5% ( n=29/31 ) and 90.6% ( n=29/32 ), respectively.

Additionally, results from the first cohort of ongoing open-label phase 2 study, CORAL-I, were presented and published in The New England Journal of Medicine ( NEJM ). Results showed that non-cirrhotic liver transplant patients with recurrent GT1 HCV and new to treatment after transplantation achieved a SVR12 rate of 97.1% ( n=33/34 ) and a sustained virologic response rate 24 weeks post-treatment ( SVR24 ) of 97.1% ( n=33/34 ) after 24 weeks of treatment.

TURQUOISE-I is a phase 2/3, multicenter, randomized, open-label study evaluating the efficacy and safety of AbbVie's all-oral, Interferon-free investigational treatment combining three direct-acting antivirals ( Ombitasvir, ABT-450 / Ritonavir and Dasabuvir ) with Ribavirin ( weight based dosing of 1000 mg or 1200 mg per day divided twice daily ) for 12 or 24 weeks in adult patients with chronic GT1 HCV infection with or without compensated liver cirrhosis who are also infected with HIV-1.
Study patients were either new to therapy ( treatment naïve ) or had failed previous treatment with pegylated Interferon and Ribavirin ( treatment-experienced ), had a stable immune status ( CD4+ counts of greater than or equal to 200 cells/mm3 or CD4+ % greater than or equal to 14% ) and had HIV-1 ribonucleic acid levels suppressed on a stable Atazanavir- or Raltegravir-based antiretroviral HIV therapy.

No patients discontinued treatment due to adverse events in either the 12-week or 24-week arm. In the 12-week arm, no virologic breakthroughs were observed while on treatment. One patient ( 3.3% ) experienced post-treatment relapse after 12 weeks of treatment.

In the 24-week treatment arm, one virologic breakthrough was observed ( 3.1% ). Two patients in the 24-week treatment group were believed to have been re-infected post-treatment by a different strain of HCV than the original infection.

The most commonly reported adverse events ( greater than 15% in both treatment arms combined ) were fatigue ( 47.6% ), insomnia ( 19% ), nausea ( 17.5% ), and headache ( 15.9% ).
Elevations in total bilirubin were the most common laboratory abnormality ( 68.3% ), were mainly composed of indirect bilirubin, and were not associated with aminotransferase elevations.
Reductions in Ribavirin dose because of anemia or reduced hemoglobin occurred in 9.5% of patients ( n=6/63 ); all six patients achieved SVR12.

CORAL-I is a phase 2, multicenter, two-cohort, open-label study evaluating the efficacy and safety of AbbVie's all-oral, Interferon-free investigational treatment combining three direct-acting antivirals ( Ombitasvir, ABT-450 / Ritonavir and Dasabuvir ) with Ribavirin ( Ribavirin dosing left up to the discretion of the investigator ) for 24 weeks in adult non-cirrhotic ( screening biopsy Metavir score less than or equal to F2 ) liver transplant recipients with recurrent chronic GT1 HCV infection.
Patients in the study initiated therapy at least 12 months after receiving a liver transplant, had not received other HCV therapy since their liver transplant, and were on a stable immunosuppressant regimen based on either Tacrolimus or Cyclosporine, for which dose adjustments were advised. Enrollment in the second cohort of the study is ongoing.

One patient ( 2.9% ) discontinued the study due to adverse events but still achieved SVR12. Two patients experienced serious adverse events.
The most commonly reported treatment-emergent adverse events ( greater than 20% ) were fatigue ( 50% ), headache ( 44.1% ), cough ( 32.4% ), anemia ( 29.4% ), diarrhea ( 26.5% ), insomnia ( 26.5% ), asthenia ( 23.5% ), nausea ( 23.5% ), muscle spasms ( 20.6% ), and rash ( 20.6% ).

No patients experienced virologic breakthrough while on treatment; however, one patient experienced post-treatment relapse.
Nine patients had a grade 2 reduction in hemoglobin, and one patient had a grade 3 reduction. Five patients with hemoglobin decreases ( anemia ) received a medication to boost their red blood cell production at the investigator's discretion.
No patients discontinued study drugs because of anemia, required a blood transfusion, or experienced a rejection of their transplanted liver.

AbbVie's investigational three direct-acting antiviral treatment consists of the fixed-dose combination of ABT-450 / Ritonavir ( 150/100 mg ) co-formulated with Ombitasvir ( 25mg ), dosed once daily, and Dasabuvir ( 250mg ) dosed twice daily with or without Ribavirin.
The combination of three direct-acting antivirals, each with a distinct mechanism of action, targets and inhibits specific hepatitis C virus proteins in the viral replication process. ( Xagena )

Source: Abbvie, 2014