Results of 2 Phase 2 Trials

[pooh55811]

Medscape Medical News
HCV Therapy: High Rate of Viral Clearance, No Injections

Two phase 2, open-label studies evaluating the safety and efficacy of all-oral combination therapies for patients infected with hepatitis C virus (HCV) have shown that high rates of sustained virologic response (SVR) are possible even in the absence of interferon. Results from both studies were published in the January 16 issue of the New England Journal of Medicine.

Patients enrolled in both studies were between 18 and 70 years of age with no evidence of cirrhosis.

In the first study, Mark S. Sulkowski, MD, from Johns Hopkins University, Baltimore, Maryland, and colleagues evaluated the efficacy of combination therapy with once-daily, oral antiviral drugs daclatasvir (60 mg daily) and sofosbuvir (400 mg daily) for patients infected with HCV genotypes 1, 2, or 3. Patients were treated for 24 weeks, and use of ribavirin as part of the treatment protocol was optional.

The US Food and Drug Administration recently approved sofosbuvir for the treatment of HCV in combination with ribavirin or ribavirin and interferon, depending on the HCV genotype being treated. Daclatasvir remains an investigational agent.

Overall, 211 patients enrolled in the study. Among those with genotype 1 infection, 126 were previously untreated and 41 had failed previous therapy with telaprevir or boceprevir plus peginterferon alfa-ribavirin.

Among patients with HCV genotype 1, researchers found that 164 (98%) previously untreated patients and 40 (98%) patients who had failed traditional therapy demonstrated a SVR (HCV RNA < 25 IU/mL) at week 12 after the end of therapy. High rates of SVR were also noted at week 12 among patients with HCV genotype 2 (92% of 26 patients) and those with HCV genotype 3 (89% of 18 patients).

"Our study shows that the combination of an NS5A inhibitor and an NS5B inhibitor was associated with high cure rates in a range of HCV-infected patients, including patients who had persistent HCV variants conferring resistance to protease inhibitors after unsuccessful treatment with telaprevir or boceprevir," write Dr. Sulkowski and colleagues.

The authors note that response rates were similar between patient groups treated with or without ribavirin; however, patients treated with ribavirin demonstrated a greater decrease in hemoglobin.

The second study evaluated an 8-, 12-, and 24-week all-oral, interferon-free treatment regimen among 571 patients with HCV genotype 1 who were previously untreated or who had failed prior therapy. The study, led by Kris V. Kowdley, MD, from the Virginia Mason Medical Center, Seattle, Washington, evaluated various dosage combinations of the NS3/4A protease inhibitor ABT-450 with ritonavir (ABT-450/r), combined with nonnucleoside NS5B polymerase inhibitor ABT-267, ABT-333, or both. All but 1 subgroup also received ribavirin.

The researchers found that SVR ranged from 83% to 100% across all treatment groups. The SVR at 24 weeks among previously untreated patients administered ABT-450/r plus ribavirin was 88% among those treated for 8 weeks and 95% among those treated for 12 weeks. Treatment beyond 12 weeks did not appear to confer any additional benefit.

HCV Therapy Without Injections

"The current standard of care for chronic HCV genotype 1 infection is pegylated interferon (peginterferon) and ribavirin, with a protease inhibitor (boceprevir or telaprevir)," write Dr. Kowdley and colleagues. The emergence of new oral antiviral therapies could mean the end of multipill and injectable drug regimens.

In an interview with Medscape Medical News, William Balistreri, MD, from the Cincinnati Children's Hospital Medical Center in Ohio, said: "[T]hese 2 preliminary studies are clearly promising, offering the hope for a 'cure' of chronic hepatitis C with a less complex, shorter-duration, interferon-free, all-oral regimen."

A similarity between the studies was the finding that both treatment-naive patients and those who had failed previous therapy demonstrated high rates of SVR with these oral, interferon-free regimens. In previous studies, "only approximately one third of patients who had not had a response to prior therapy with peginterferon and ribavirin had a sustained virologic response when re-treated with the addition of a protease inhibitor," write Dr. Kowdley and colleagues. These findings provide hope that these newer regimens may be of benefit in difficult-to-treat patients with HCV.

Adverse effects were similar between the studies and included fatigue, headache, and nausea; they compare favorably with the rate of adverse effects previously documented with standard HCV therapy.

Although the results of both studies offer hope to patients infected with HCV, "[w]e await 'real-world' experience with these [agents], once full approval and widespread use occur. This will include reports of barriers encountered, including cost, efficacy, and adverse effects," concluded Dr. Balistreri.

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[jules2551]

Thanks for posting this! Great news for many.  Jimmy i liked yours also until I saw the exclusion criteria...hemochromatosis.  These trials sound promising.  

Its time to start my own trials...Clyde and Thelma are you game :)

[JimmyMose]

Yes they usually want the best test subjects for Phase II  Hopefully this new Phase III trial will show good results too.

Phase III Daclatasvir + Sofosbuvir in Cirrhotic Subjects and Subjects Post-liver Transplant (ALLY 1)
This study is not yet open for participant recruitment.
This trial is open to patients with cirrhosis due to chronic HCV, and to patients who have already received a liver transplant for chronic HCV. All subjects will be treated with Daclatasvir and Sofosbuvir for 12 weeks. Under certain conditions, the treatment duration may be extended for cirrhotic subjects. The study will test how well this combination of investigational drugs works to treat chronic HCV.

Sponsor:Bristol-Myers Squibb  (and we know why Gilead doesn't care)

Estimated Enrollment: 110
Study Start Date: March 2014
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)

Inclusion Criteria:
Subjects must be able to understand and agree to comply with the prescribed dosing regimens and procedures, report for regularly scheduled study visits, and reliably communicate with study personnel about adverse events and concomitant medications
Subjects chronically infected with HCV Genotype 1, 2, 3, 4, 5, or 6 with HCV RNA viral load of ≥ 10,000 IU/mL at screening
Subjects may be treatment-naïve or treatment-experienced
Cirrhotic subjects must have cirrhosis confirmed by biopsy, Fibroscan or fibrotest and Aspartate aminotransferase platelet ratio index (APRI) criteria as outlined in the protocol
Post-transplant subjects must be at least 3 months post-transplant with no evidence of moderate or severe rejection
Exclusion Criteria:

History of multi-organ transplant, with the exception of dual transplantation of the liver/kidney, is prohibited
Current or known history of cancer (with the following exceptions: In situ carcinoma of the cervix, adequately treated basal or squamous cell carcinoma of the skin, or hepatocellular carcinoma within Milan criteria for transplantation) within 5 years prior to screening
Evidence of an ongoing medical condition contributing to chronic liver disease other than HCV (such as, but not limited to: hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, or toxin exposures)
History of HIV infection or chronic hepatitis B virus (HBV) as documented by HBV serologies (e.g., HBsAg-seropositive). Subjects with resolved HBV infection may participate (e.g., HBcAb-seropositive with concurrent HBsAg-seronegative)
Active hospitalization for decompensated liver disease

http://clinicaltrials.gov/ct2/show/NCT02032875?recr=Not+yet+recruiting&cond=Hepatitis+C&phase=123&lup_s=01%2F01%2F2014&rank=2