Clinical Trials

AMAR’s ongoing clinical development programs for oral interferon include treatment of influenza and hepatitis C.

Influenza

Clinical studies have demonstrated that low doses of intranasal or oral interferon are safe and effective at preventing or treating influenza. In the former Soviet Union, approximately 14,000 people participated in controlled studies of placebo versus interferon treatment during a natural outbreak of Hong Kong influenza. Interferon (about 128 units) or placebo was dripped into the nose daily for 5 days starting about the time of the first reported influenza cases. Interferon treatment significantly reduced the number of influenza cases (P<0.01 for all age groups).

The University of Western Australia in Perth conducted a Phase 2 clinical study of oral IFN as prevention/treatment of respiratory illnesses, including influenza during the winter cold/flu season in 2009. A total of 200 healthy volunteers were enrolled to take oral IFN or placebo lozenges once daily for 16 weeks. Once per week, the study volunteers completed a questionnaire detailing the severity of any cold/flu symptoms experienced, any medications taken, number of days of work missed, etc.

Overall, the incidence of serologically confirmed viral infections (influenza and non-influenza) was the same in both the interferon-alpha and placebo groups. However, the proportion of seropositive participants who reported moderate to severe cold/flu symptoms was 76.2% in the placebo group, compared to only 23.8% in the interferon-alpha group (p=0.0082), indicating that, while prophylaxis with interferon-alpha lozenges did not reduce the incidence of infection, it did significantly reduce the incidence of moderate to severe viral respiratory illness.

Interferon prophylaxis had a significant impact on the reporting of moderate to severe feverishness by the study population. For moderate to severe symptoms, feverishness was significantly reduced from an incidence of 23.3% in the placebo group to only 11.7% in the IFN group (p=0.036). Similar trends were observed in the reduction of moderate to severe head congestion (p=0.053) and sore throat (p=0.056). 

Post hoc analysis identified significant reductions in the incidence of acute respiratory illness reported by participants who were male, aged 50 years or more, or received the 2009 seasonal influenza vaccine. The apparent beneficial effect in study participants who had received the seasonal vaccine suggests that treatment with interferon-alpha lozenges may have improved cross-protection against the pandemic influenza A (H1N1) 2009 strain following seasonal influenza vaccination.

In Taiwan, approximately 40 patients being treated with Tamiflu for influenza A infection of less than 48 hours’ duration were randomly assigned to co-treatment with oral IFN or placebo. The aim of the study is to examine whether the combination of oral IFN and Tamiflu is superior to Taimflu alone in the treatment of influenza illness. Results are expected in early 2013. For more information on this study, please visit:

http://www.clinicaltrials.gov/ct2/show/NCT01146535

Hepatitis C

A Phase 2, placebo-controlled, dose-ranging study of 169 hepatitis C virus-infected patients was conducted in Taiwan. The study was designed to test the ability of oral IFN to reduce the virologic relapse rate of patients who have completed standard therapy with pegylated IFN plus ribavirin. Up to 50% of patients with certain genotypes of HCV relapse after receiving standard therapy. Reduction of the relapse rate by oral IFN would represent a major breakthrough in the management of hepatitis C. Treatment time in the study was 6 months with another 6 months of untreated observation.

The overall rate of virologic relapse was lower in both IFN groups (~30%), compared to placebo (33%), but the difference was not statistically significant. The study failed to achieve the hoped for 50% reduction in relapse rate. However in the sub-group of subjects who started the study with a low level of liver fibrosis (scarring) as indicated by their FibroIndex score (about 40% of the evaluable study population), the rate of virologic relapse was reduced by more than half in the 500 IU group (12%), compared to the placebo group (32%). Due to small numbers, this difference was not highly significant (P=0.14), so this finding will need to be confirmed in a larger study of HCV patients with mild fibrosis.

In the sub-group of subjects who started the study with a low platelet count (about 60% of the evaluable study population), statistically significant increases in platelets were observed in the 500 IU group during both the treatment and post-treatment observation phases, compared to the placebo group. By the end of the study, 81% of subjects in the 500 IU group who had a low platelet count at entry experienced normalization of their platelet count, compared to only 42% of the subjects in the placebo group (P=0.005). The apparent ability of oral IFN to reverse thrombocytopenia has implications, not only for use as HCV maintenance therapy, but in a number of other indications in which the underlying disease or commonly used treatments lead to depressed platelet counts.

While this study did not achieve its primary goal of reducing relapse by 50% in HCV patients who entered viral remission following standard therapy, there are reasons to be optimistic. First, this study detected that maintenance therapy with oral IFN can potentially lower the virologic relapse rate in HCV patients with mild fibrosis. It also appears that oral IFNα could be useful in restoring depressed platelet counts in HCV patients who have undergone treatment with injectable IFN. This latter important finding has application in a number of other diseases and treatment regimens that cause thrombocytopenia. Further studies to confirm and expand the beneficial findings from this study are clearly warranted.

Safety of oral IFN was excellent in this study. There were no increases in adverse event incidence or severity in the IFN groups, compared to placebo, and there was no increase in the rate of early study drop-outs. For more information on this study, please visit:

http://clinicaltrials.gov/ct2/show/NCT00695019

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