Identifying Clinical Studies for Patients With Hepatitis C

At least 8 phase III clinical trials in the United States were recruiting participants for studies of treatments for chronic hepatitis C virus (HVC) infection as of late June 2014.^1-8

Clinical trials offer many patients the opportunity to receive treatment with cuttingedge medications for little to no cost. Phase III trials are often conducted at multiple clinical trial centers throughout the United States and expose patients to a lower risk of unexpected adverse events due to the fact that treatments that reach phase III development have already been tested in phase I and phase II trials. As a result, investigators have a fair idea of the efficacy and safety of medications involved in the trials.

Exclusion criteria, specific requirements, and geographic criteria often make it challenging for patients to learn about clinical trials and consider them as a treatment option. Sifting through trial data to find an acceptable trial option may leave patients confused and, due to time constraints, may leave physicians unable to help identify qualifying clinical trials.

Currently, 3 companies—AbbVie, Merck, and Bristol-Myers Squibb—are sponsoring late-stage trials for 3 new combination medications for treatment of chronic HCV infection. Patients in the United States are presently being recruited.^1-8

3D Combination (sponsored by AbbVie): The “3D” combination includes 3 medications: the protease inhibitor ABT-450, ritonavir, and the NS5A ombitasvir (ABT-267). Initial responses indicate sustained virologic response (SVR) rates in the high 90% range in patients with genotype 1 chronic HCV infection, regardless of unfavorable predictors of treatment response, including cirrhosis and failure on previous therapy. Common adverse events have included nausea, pruritus, insomnia, diarrhea, and asthenia.^9-12

Recruiting phase III trials include^1,2:

• NCT02167945: A Study to Evaluate Long-term Outcomes Following Treatment With ABT-450/ Ritonavir/ABT-267 (ABT-450/r/ABT-267) and ABT- 333 With or Without Ribavirin (RBV) in Adults With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection
• NCT01939197: A Study to Evaluate the Safety and Efficacy of ABT-450/Ritonavir/ABT-267 (ABT-450/r/ ABT-267) and ABT-333 Coadministered With Ribavirin (RBV) in Adults With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection and Human Immunodeficiency Virus, Type 1 (HIV-1) Coinfection

MK-5172/MK-8742 (sponsored by Merck): MK-5172, a macrocyclic NS3/4A protease inhibitor, and MK-8742, a NS5A inhibitor, are an orally active combination of direct-acting antivirals expected to be more active than other agents against multidrug-resistant variants of HCV.^13,14

Recruiting phase III trials include ^3-7:

• NCT02092350: Safety and Efficacy of MK-5172 + MK-8742 in Participants With Chronic Hepatitis C and Chronic Kidney Disease (MK-5172-052) • NCT02115321: Study of Efficacy and Safety of MK- 5172 + MK-8742 in Chronic Hepatitis C Participants With Child-Pugh (CP)-B Hepatic Insufficiency (MK- 5172-059)
• NCT02105662: An Efficacy and Safety Study of MK-5172 + MK-8742 in the Treatment of Chronic Hepatitis C Virus in Participants Who Are Co- Infected With Human Immunodeficiency Virus (C-EDGE COINFECTION) (MK-5172-061)
• NCT02105467: Study of Efficacy and Safety of MK-5172/MK-8742 Combination Regimen for Treatment-Naïve Participants With Chronic Hepatitis C Virus Genotypes 1, 4, 5, and 6 (MK-5172- 060)
• NCT02105701: Study of Efficacy and Safety of MK- 5172 + MK-8742 With or Without Ribavirin for Participants With Hepatitis C Genotype 1, 4, 5, or 6 Infections Who Have Failed Prior Treatment With Pegylated Interferon + Ribavirin (MK-5172-068)

Daclatasvir/ Interferon Lambda-1a/Ribavirin (sponsored by Bristol-Myers Squibb): Interferon lambda-1a has demonstrated clinical efficacy in HCV genotypes 1 through 4. By combining this form of interferon with the NS5A replication complex inhibitor daclatasvir and ribavirin, synergistic effects are expected, particularly in clearing genotype-1a CHC infection.¹⁵

Recruiting phase III trials include ⁸:

• NCT01866930: Efficacy and Safety Study of Pegylated Interferon Lambda-1a With Ribavirin and Daclatasvir, to Treat Naïve Subjects With Chronic HCV Genotypes 1, 2, 3, and 4 Who Are Co-infected With HIV (DIMENSION)

References:

1. ClinicalTrials.gov. A study to evaluate long-term outcomes following treatment with ABT-450/ritonavir/ABT-267 (ABT- 450/r/ABT-267) and ABT-333 with or without ribavirin (RBV) in adults with genotype 1 chronic hepatitis C virus (HCV) infection. http://clinicaltrials.gov/show/NCT02167945. Accessed June 27, 2014.

2. ClinicalTrials.gov. A study to evaluate the safety and efficacy of ABT-450/ritonavir/ABT-267 (ABT-450/r/ABT-267) and ABT- 333 coadministered with ribavirin (RBV) in adults with genotype 1 chronic hepatitis C virus (HCV) infection and human immunodeficiency virus, type 1 (HIV-1) coinfection. http:// clinicaltrials.gov/show/NCT01939197. Accessed June 27, 2014.

3. ClinicalTrials.gov. Safety and efficacy of MK-5172 + MK-8742 in participants with chronic hepatitis C and chronic kidney disease (MK-5172-052) (C-SURFER). http://www.clinicaltrials .gov/show/NCT02092350. Accessed June 27, 2014.

4. ClinicalTrials.gov. Study of efficacy and safety of MK-5172 + MK-8742 in chronic hepatitis C participants with Child-Pugh (CP)-B hepatic insufficiency (MK-5172-059). http://www.clinicaltrials. gov/ct2/show/NCT02115321. Accessed June 27, 2014.

5. ClinicalTrials.gov. An efficacy and safety study of MK-5172 + MK-8742 in the treatment of chronic hepatitis C virus in participants who are co-infected with human immunodeficiency virus (C-EDGE COINFECTION) (MK-5172-061). http://clinicaltrials. gov/show/NCT02105662. Accessed June 27, 2014.

6. ClinicalTrials.gov. Study of efficacy and safety of MK-5172/ MK-8742 combination regimen for treatment-naïve participants with chronic hepatitis C virus genotypes 1, 4, 5, and 6 (MK-5172-060). http://clinicaltrials.gov/show/NCT02105467. Accessed June 27, 2014.

7. ClinicalTrials.gov. Study of efficacy and safety of MK-5172 + MK-8742 with or without ribavirin for participants with hepatitis C genotype 1, 4, 5, or 6 infections who have failed prior treatment with pegylated interferon + ribavirin (MK- 5172-068). http://clinicaltrials.gov/show/NCT02105701. Accessed June 27, 2014.

8. ClinicalTrials.gov. Efficacy and safety study of pegylated interferon lambda-1a with ribavirin and daclatasvir, to treat naïve subjects with chronic HCV genotypes 1, 2, 3, and 4 who are co-infected with HIV (DIMENSION). http://clinicaltrials.gov/ show/NCT01866930. Accessed June 27, 2014.

9. Feld JJ, Kowdley KV, Coakley E, et al. Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. N Engl J Med. 2014;370(17):1594-1603.

10. Zeuzem S, Jacobson IM, Baykal T, et al. Retreatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. N Engl J Med. 2014;370(17):1604-1614.

11. Poordad F, Hezode C, Trinh R, et al. ABT-450/r-ombitasvir and dasabuvir with ribavirin for hepatitis C with cirrhosis. N Engl J Med. 2014;370(21):1973-1982.

12. Ferenci P, Bernstein D, Lalezari J, et al. ABT-450/r-ombitasvir and dasabuvir with or without ribavirin for HCV. N Engl J Med. 2014;370(21):1983-1992.

13. Summa V, Ludmerer SW, McCauley JA, et al. MK-5172, a selective inhibitor of hepatitis C virus NS3/4a protease with broad activity across genotypes and resistant variants. Antimicrob Agents Chemother. 2012;56(8):4161-4167.

14. De Clercq E. Current race in the development of DAAs (direct-acting antivirals) against HCV. Biochem Pharmacol. 2014;89(4):441-452.

15. Friborg J, Levine S, Chen C, et al. Combinations of lambda interferon with direct-acting antiviral agents are highly efficient in suppressing hepatitis C virus replication. Antimicrob Agents Chemother. 2013;57(3):1312-1322.