Clinical Trials Resource Center

New Medical Therapies™

Influenza

September 29, 2014

Novavax released results of a phase I/II study of its H7N9 Avian Influenza VLP Vaccine Candidate H7N9 VLP with proprietary adjuvant Matrix-M. The study was conducted in 610 healthy subjects to evaluate the safety and immunogenicity of the H7N9 VLP with Matrix-M. The study was a dose-ranging, randomized, observer-blinded, placebo-controlled clinical trial to determine the contribution of Matrix-M to potential antigen dose-sparing regimens. Subjects were administered two identical doses of either placebo, 15μg of H7N9 VLP alone, or 3.75μg, 7.5μg or 15μg of H7N9 VLP in combination with either 25μg or 50μg of Matrix-M. Serology was taken on day zero, 21 and 42. The H7N9 VLP, with and without Matrix-M, was well-tolerated and demonstrated a safety profile similar to the company’s prior experience with another saponin-based adjuvant. Matrix-M adjuvanted formulations demonstrated a clear immunogenicity benefit relative to unadjuvanted antigen and a dose-response within the adjuvanted groups. Antigen dose-sparing was shown, such that even the 3.75μg dose of antigen with either tested dose of adjuvant gave immune responses statistically significantly greater than 15μg dose without adjuvant. The vaccine also elicited anti-neuraminidase (NAI) antibodies against N9, with 89 to 100% sero-response rates in the adjuvanted vaccine groups, and greater than 11-fold increases in geometric mean titers. Further clinical studies are being considered.

August 25, 2014

Sanofi Pasteur reported results from a large-scale, multi-center efficacy trial, which found that Fluzone High-Dose (Influenza Vaccine) was more efficacious in preventing influenza in adults 65 years of age and older compared to standard-dose Fluzone vaccine. Investigators compared the vaccine’s efficacy in a randomized, double-blind trial that spanned two influenza seasons. The trial enrolled nearly 32,000 participants; 14,500 and 17,489 adults 65 years of age and older during the 2011- 2012 and 2012-2013 influenza seasons, respectively, from 126 research centers in the U.S. and Canada. 228 people in the Fluzone High-Dose vaccine group (1.43%) and 301 people in the standard-dose Fluzone vaccine group (1.88%) had laboratory-confirmed influenza, demonstrating Fluzone High-Dose vaccine was 24.2% (95% CI, 9.7 to 36.5) more effective in preventing influenza than standard-dose Fluzone vaccine. Additionally, researchers determined most rates for pneumonia, cardio-respiratory conditions, hospitalizations, non-routine medical office visits and medication use were lower for the Fluzone High-Dose vaccine group compared to the standard-dose Fluzone vaccine group. These results formed the basis of an FDA regulatory submission late last year to seek a modification to the prescribing information for Fluzone High-Dose vaccine reflecting the improved efficacy compared to standarddose Fluzone vaccine in adults 65 years of age and older. Sanofi Pasteur anticipates a decision later this year.

August 27, 2012

Biota and Daiichi Sankyo released results from a phase III trial of Inavir for the prevention of influenza. This multi-center, placebo-controlled, double-blinded study enrolled 1,500 patients within a family with a confirmed sufferer of influenza A or B. Contracted influenza was defined by an elevated body temperature, a positive measure of influenza virus in a PCR diagnostic assay and the display of at least two of the following symptoms: headache, muscle or joint pain, fatigue, chill or perspiration, nasal discharge, sore throat or cough. Results demonstrated that, compared to placebo, Inavir significantly reduced the proportion of patients contracting either strain of influenza in the household (p<0.0001). Furthermore, Inavir produced protective efficacies in excess of 70%. The drug was well tolerated. Based on these data, Daiichi Sankyo intends to apply for approval to market Inavir for the prevention of influenza before the end of 2012.

January 17, 2011

BioCryst Pharmaceuticals reported results from a phase III trial of intravenous (i.v.) peramivir for the treatment of influenza. The open-label, randomized trial (303) enrolled 234 subjects aged 14 to 92 years who were hospitalized during the 2009-2010 H1N1 pandemic, 200 (85%) of whom had a duration of illness of more than 48 hours. The subjects received peramivir administered either as a once-daily infusion of 600 mg or a twice-daily infusion of 300 mg for a median duration of five days. The primary endpoint was the change in influenza virus titer in nasopharyngeal samples, measured by log10 tissue culture infective dose50 (TCID50). Similar reductions in log10 TCID50 viral titer were observed over the first 48 hours in the two treatment groups, -1.66 for the twice-daily arm and -1.47 for the once-daily arm. Both dose regimens were generally safe and well-tolerated.

September 7, 2009

Novavax reported positive results from a phase II trial of their seasonal influenza virus-like particle (VLP) vaccine candidate. This randomized, blinded, placebo-controlled study enrolled 221 healthy adult subjects between the ages of 18 to 49 years. The subjects receive a single injection of either a placebo or influenza vaccine at doses of 15 mcg or 60 mcg. The vaccine contained three VLPs (H3N2, H1N1, and B) that were matched to the strains recommended for influenza vaccines for the past flu season (2008-2009). An additional 20 subjects received Fluzone, a licensed, egg-based influenza vaccine. Novavax's influenza VLP vaccine candidate was well tolerated and no vaccine-related serious adverse events were reported. The VLP vaccine also induced strong hemagglutination inhibition (HAI) antibody responses against the influenza H1N1, H3N2, and B strains. Seroconversion rates (percentage of subjects with a 4-fold or higher rise in HAI titer from baseline) ranged from 81-86% for H3N2, 57-66% for H1N1, and 62-67% for B for subjects with and without existing antibody before vaccination. The subjects who received Novavax's VLP vaccine had higher antibody responses against the H3N2 virus that was circulating in the community than recipients of Fluzone.

August 17, 2009

Daiichi Sankyo issued positive results from a phase III trial of laninamivir for the treatment of influenza A or B. This double-blind, non-inferiority study, dubbed MARVEL (Multinational Asian Clinical Research for Influenza Virus Extermination on LANI), enrolled 1,000 adult subjects with confirmed, naturally acquired influenza A or B. The study was designed to confirm that the non-inferiority of a single inhalation of CS-8958 20 or 40 mg to oseltamivir capsule (TamiFlu) 75 mg administered orally twice daily for 5 consecutive days. Non-inferiority was confirmed in both the 20 mg and 40 mg groups of laninamivir in terms of the primary endpoint, time to alleviation of influenza illness. The 40 mg group of was superior to 20 mg group in efficacy. Both 20 mg and 40 mg of CS-8958 were well tolerated.

July 27, 2009

BioCryst and Shionogi issued positive results from two phase III trials of peramivir for the treatment of uncomplicated and complicated seasonal influenza. Both trials were conducted during the 2008-2009 influenza season. Uncomplicated Seasonal Influenza: This three-armed, multi-center, randomized, double-blind, multi-national study enrolled 1,099 subjects across Japan, Taiwan and Korea. The subjects received a single dose of peramivir (either 300 mg or 600 mg) or oral oseltamivir phosphate 75 mg (Tamiflu) twice a day for five days. The primary endpoint was non-inferiority in time to alleviation of symptoms (TTAS). Both doses of peramivir demonstrated non-inferiority compared to the oseltamivir group; the median for TTAS for the peramivir 300 mg and 600 mg and oseltamivir groups were 78.0 hours, 81.0 hours and 81.8 hours, respectively. Complicated Influenza: This double-blind, multi-center study enrolled 42 subjects with influenza at high-risk of serious complications due to one or more conditions: poorly controlled diabetes mellitus, a chronic respiratory disease or current treatment with any immunosuppressive drug. The subjects received peramivir administered at 300 mg or 600 mg per day, and the duration was adjusted (up to five days) on a case-by-case basis, depending on the patient's temperature and clinical condition. In 37 evaluable subjects treated with either of the peramivir daily doses, the median time to alleviation of symptoms was 68.6 hours.

March 31, 2008

Iomai reported positive interim results from a phase I/II trial of their influenza vaccine patch in combination with an injected H5N1 influenza vaccine. This study enrolled five hundred subjects who received an egg-derived H5N1 influenza vaccine, the adjuvant vaccine patch and placebo to determine which combinations would be most effective in a two-immunization regimen, administered twenty-one days apart. Of fifty subjects vaccinated a single time with a 45-microgram dose in combination with the Iomai patch, 92% had an immune response. Seventy-three percent of these subjects achieved an HI titer of greater than 40, a value which may eliminate the need for a second vaccination. Of the subjects who received the vaccine alone, without a patch, 49% had an immune response considered protective after the first dose. The difference between the patch and no-patch groups was statistically significant (p<0.0001). A second dose of both vaccine and patch further enhanced immunogenicity; 100% of subjects who received two 45-microgram doses of vaccine and two Iomai patches had a measurable immune response, and 94% of subjects had immune responses considered protective. Treatment was well tolerated, with no adverse events reported. Based on the results, Iomai will continue on with the trial as planned.

January 14, 2008

Novavax reported positive interim results from a phase I trial of their VLP pandemic influenza vaccine. The initial stage of this study enrolled seventy healthy subjects, aged eighteen to forty years, who received two doses of either 15 or 45 mcg of the VLP vaccine candidate or a placebo. The primary endpoints were safety and immunogenicity, including hemagglutinin inhibition (HAI) and neutralizing antibody responses. The vaccine was well tolerated in all treatment arms. In the 45 mcg arm, 83% had neutralizing antibody against the H5N1 A/Indonesia/05/2005 avian flu strain after the second vaccination. A 4-fold rise in neutralizing antibody from baseline was observed in 63% of the subjects. In regard to HAI responses, 48% had a 4-fold increase in titer from baseline. All subjects tested negative for antibodies to the H5N1 Indonesia strain before vaccination and no responses were observed among individuals who received a placebo. The vaccine also induced responses against the A/Viet Nam/1203/2004 avian flu strain. In 15 mcg dose arm 75% of the subjects had neutralizing antibody against the Indonesia strain. Based on the results, the next stage of the trial has commenced whereby the safety and immunogenicity of vaccine doses up to 90 mcg will be assessed.

August 6, 2007

AlphaVax released positive results from a phase I trial of their influenza vaccine. This placebo-controlled, randomized, double-blind study enrolled 216 healthy subjects who received a single dose of the vaccine at one of two dose levels. Data was taken four weeks after vaccine administration. Protective HI serum antibody titers were observed in 77% of the low dose and 80% of the high dose cohorts who had pre-vaccination influenza serum antibody titers (measured by hemagglutination inhibition, or "HI") that were below levels deemed protective against influenza infection. Based on the results, AlphaVax plans to move forward with the development of their influenza vaccine.

Incyte announced positive results from a phase IIa trial of INCB9471 for the treatment of HIV. This placebo-controlled trial enrolled 23 treatment-naive or treatment-experienced HIV-infected subjects harboring R5-tropic virus. Subjects received INCB9471 200 mg once-daily or placebo for 14 days. Subjects receiving INCB9471 showed rapid and prolonged reduction in viral load with a mean maximal decline of 1.81 log10 at day 16. The viral load continued to be suppressed well beyond the 14-day dosing period, with a mean 0.81 log10 decline in viral load observed at day 28. CD4+ cell counts were stable or slightly increased over the 14 day treatment period. Based on the results, two phase IIb trials are planned for early 2008.

Pfizer reported positive results from a phase III trial of maraviroc for the treatment of HIV. This 48-week trial was dubbed MERIT (maraviroc versus Efavirenz Regimens as Initial Therapy) and enrolled CCR5-tropic HIV-1 infected subjects who had never received antiretroviral therapy and had no evidence of resistance to the drugs used in the study. MERIT was designed to compare maraviroc (300 mg twice daily) to efavirenz, standard of care, (600 mg once daily), both dosed in combination with zidovudine/lamivudine. In the full set analysis, the rates of virologic suppression were 70.6% and 73.1% for the maraviroc and efavirenz groups, respectively, for less than 400 copies/ml and 65.3% vs. 69.3%, respectively, at less than 50 copies/ml. Increases in CD4+ cell counts from baseline were also greater with maraviroc (+170 cells/mm3) than with efavirenz (+144 cells/mm3). In addition, fewer subjects in the maraviroc arm experienced Grade 3 or 4 adverse events compared to the efavirenz group. The FDA issued an approvable letter for maraviroc in June of 2007.

Schering-Plough issued positive long-term data from a phase II trial of vicriviroc for the treatment of HIV. This randomized, double blind study enrolled 118 HIV infected, treatment-experienced subjects. Treatment administration was vicriviroc (5, 10 and 15 mg) or placebo, in combination with an optimized ritonavir-boosted protease inhibitor-containing antiretroviral regimen, once daily. This data was from 48-weeks post-treatment. Subjects in the 10 mg and 15 mg vicriviroc treatment groups achieved a median decrease in viral load of 1.92 and 1.44 (log10 copies/mL) and a median increase in CD4 cell count of 130 and 96 (cell/uL) from baseline, respectively. Subjects in the vicriviroc groups had undetectable virus at 48 weeks (HIV-1 RNA <400/<50 copies/ml) compared to those in the placebo group and fewer subjects in the vicriviroc groups experienced virological failure compared to those in the placebo group (27% and 33% versus 86%, respectively). This randomized, double blind study enrolled 118 HIV infected, treatment-experienced subjects. Treatment administration in this trial was vicriviroc (5, 10 and 15 mg), or placebo, in combination with an optimized ritonavir-boosted protease inhibitor-containing antiretroviral regimen, once daily.

June 4, 2007

Iomai issued mixed interim results from a phase I trial of their influenza vaccine patch for the treatment of seasonal influenza. This randomized, double-blind trial enrolled 353 subjects who received an injected intramuscular vaccine or the Iomai patch. Both vaccines contained the same three flu antigens. Results showed that the patch stimulated an immune response to each of the three antigens in a dose-dependent manner. However, the injected vaccine prompted a greater immune response when compared with the patch vaccine. Based on the results Iomai plans to add an immune-boosting adjuvant to the vaccine patch and move forward with further development.

October 9, 2006

Baxter released positive preliminary results from a phase I/II trial of its vero-cell H5N1 vaccine for the treatment of influenza. This trial enrolled 270 subjects in Austria and Singapore, who were dosed with four different antigen concentrations ranging from 3.75mcg to 30mcg. Concentrations at 7.5mcg and 15mcg were tested with and without an adjuvant. The vaccine was well tolerated at all dose levels, with the most commonly reported adverse effects including injection site reaction, headache and fatigue. The vaccine was also found to be highly immunogenic, eliciting functional antibodies to H5N1 at the lowest dose level of 3.75mcg. Based on the results Baxter plans to initiate a phase III trial of the vaccine at the beginning of 2007.

July 31, 2006

GlaxoSmithKline has issued positive results of a clinical trial of their investigational H5N1 flu vaccine, under investigation for the prevention of an avian influenza pandemic. Trial data indicated that over 80% of subjects achieved seroprotective immune response (hemagglutination inhibition titer > 40) following administration of the lowest antigen dose. This open-label study enrolled 400 healthy adults in Belgium, who received two injections at one of four antigen levels (lowest: 3.8 mcg) in combination with a proprietary adjuvant.

June 5, 2006

PowderMed reported positive results of a phase I trial of their prophylactic DNA vaccine, for the treatment of influenza, in the journal Vaccine. Trial data yielded evidence of immunogenicity, with the highest trial dose eliciting seroprotective antibody responses. The level of this response for the highest dose was sufficient to meet EU CPMP immune response approvability criteria at 21 days, and all 3 doses met EU CPMP criteria at 56 days. This single ascending dose study enrolled 36 healthy volunteers, who received one of three doses of the vaccine (1 mcg, 2 mcg or 4 mcg).

Vical announced positive results of a phase I trial of their investigational West Nile Virus vaccine, at the American Society of Gene Therapy (ASGT) 2006 Annual Meeting in Baltimore. Results from the study demonstrated a positive safety profile, with no serious adverse events reported and a positive tolerability profile. Further, all subjects treated to date achieved neutralizing antibody WNV-specific responses following a 3-month vaccination schedule; a number of subjects achieved neutralizing antibody response following 2 doses. This open-label study had treated 11 healthy volunteers to date at the NIH Clinical Center; subjects received 4 mg of the vaccine once monthly for 3 months.

November 22, 2004

Boehringer-Ingelheim has reported positive results of a phase III trial of tipranavir, their investigational protease inhibitor for the treatment of HIV infections. Results from a 24-week interim analysis have indicate that the drug is efficacious in reducing viral load, with a significantly greater portion of subjects receiving tipranavir plus low-dose ritonavir (T/r) achieving treatment response (a 1 log(10) or greater decrease) than in those receiving a comparator protease inhibitor plus low-dose ritonavir (CPI/r) (41.0% vs. 14.9%; p<0.001). Furthermore, subjects receiving T/r experienced a significantly greater portion of subjects achieving preset total viral load levels of 400 copies/ml and 50 copies/ml (p<0.0001), and significant greater increases in CD4+ count (p=0.02), than in subjects taking CPI/r. The randomized, approved-therapy controlled, open-label trial was designed to study the safety and efficacy of T/r versus CPI/r, in 863 treatment-experienced patients with documented protease-inhibitor resistance. This trial, along with a second phase III study, formed the basis of the company’s NDA application, submitted on October 22, 2004.<

MacroChem has announced positive results of a phase I trial of EcoNail (SEPA plus econazole), an investigational antifungal lacquer for the treatment of onychomycosis, a common fungal infection of the nail. Trial data indicate that the study met its primary safety and pharmacokinetic endpoints, with no serious drug-related adverse events and no detectable systemic absorption. The randomized, double-blind, placebo controlled trial enrolled 18 patients suffering from onychomycosis across 2 clinical sites in the US. Subjects received twice daily applications of either EcoNail or placebo lacquer 6 weeks, and were monitored for adverse events and systemic absorption. An ongoing open-label extension is currently underway, with all patients receiving EcoNail once daily to all nails for an additional 12 weeks, and MacroChem announced plans to initiate a preliminary efficacy trial in early 2005.

PowderMed has issued results of their first phase I trial of their DNA influenza vaccine candidate. Results indicate that the trial met its primary endpoints, with all trial doses of the drug being well tolerated and a significant number of subjects exhibiting immune response sufficient to meet standards established for European approval after 56 days. Furthermore, the highest dose of the drug met the criteria after just 21 days, and 100% of subjects receiving this dose achieved seroprotective antibody levels. This open-label trial enrolled 36 healthy adult volunteers, who were randomized to receive one of three single doses of the vaccine (1, 2 and 4 micrograms), followed by a 56 day follow-up observation.

The Immune Response Corporation presented data from their ongoing phase II study of Remune, their investigational antiretroviral vaccine for the treatment of HIV, at the 7th International Congress on Drug Therapy in HIV Infection in Glasgow, Scotland. Preliminary results from the 37 subjects having thus far received treatment demonstrate positive trends in several immune-response indicators, including stabilization of total CD4+ T-cell counts, increased HIV-specific CD8+ memory T-cells, and decreased levels of activated CD38+ T-cells, following treatment. This multi-center, single-blind study has to date randomized 37 of a projected 51 treatment naïve HIV-positive subjects to receive one of two treatment regimens of Remune (one injection Remune & two placebo or three injections Remune), or Incomplete Freund's Adjuvant (a non-targeted immunostimulatory) or placebo over 28 weeks; the four arms of the study each received injections at trial initiation and weeks 12 and 24. Immune Response, following these results, has announced plans for a rollover study which will include treatment with both Remune and IR103, another of the company’s investigational antiretroviral drugs.

May 10, 2004

Protein Sciences Corporation reported positive results from a phase II b trial investigating FluBlOk, a vaccine for the prevention of influenza. Results showed that FluBlOk was safe and statistically more immunogenic against the H3 influenza strain when administered at higher doses compared with the current licensed vaccine. Data demonstrated that at least 20% more subjects receiving high doses of FluBlOk achieved antibody levels that are associated with better protection against an H3 influenza virus than subjects receiving the licensed vaccine. FluBlOk had a slightly lower rate of minor side effects than the licensed vaccine. The double-blinded study enrolled 399 elderly subjects at three sites in the U.S.

February 24, 2003

ID Biomedical reported positive preliminary results from a challenge study with FluINsure, an intranasal influenza vaccine. Data showed the trial reached both the saftey and clinical efficacy endpoints. Results showed that 86% of subjects who received two doses of vaccine achieved no illness criteria compared to 52% of subjects who received placebo. The vaccine resulted in complete elimination of all measure of systemic illness such as fever, headache, or myalgia/arthralgia in the two-dose group. The one-dose group did not attain significant differences from placebo with respect to the no illness criteria, but did show a 40% reduction in systemic illness. The randomized, blinded, placebo controlled study enrolled 75 healthy subjects. All subjects were challenged with influenza and given either one or two doses of FluINsure or placebo.

December 9, 2002

ID Biomedical reported positive results from a phase II trial investigating FluINsure, an intranasally delivered vaccine for the treatment of influenza. Statistically significant increases in serum hemagglutination-inhibiting (HAI) antibodies and nasal secretory antibody levels were reported. For both influenza A strains included in the vaccine, serum HAI antibody titers increased by an average of 2.4-fold in the one-dose group and 2.5-fold in the two-dose groups. Rises in HAI antibodies to influenza B component were lower in all groups. The double blind, placebo-controlled, randomized study enrolled 99 healthy subjects and immunized them in one or two dose regimens. FluINsure was well tolerated with no serious adverse events and mild nasal stuffiness and/or runny nose associated with the vaccine compared to placebo.

October 14, 2002

Positive phase I clinical trial results were reported for FluINsure, a nonliving flu vaccine from ID Biomedical. The study, a randomized double-blinded and placebo-controlled trial, was found to be well tolerated by healthy adults. The vaccine showed significant increases in both serum hemagglutination inhibiting (HAI) antibody and in virus-specific secretory IgA antibodies in the nose. Increases were shown for all three types of influenza viruses (A/H1N1, A/H3N2, and B) represented in the vaccine. Subjects who were administered active vaccine had an average increase in serum HAI antibody levels of 3.2-fold of normal protection levels. In a high majority of subjects, without existing immunity to the A/H1N1, A/H3N2, or B viruses, a significant serum and/or nasal antibody response was reported.

July 1, 2002

BioCryst Pharmaceuticals has decided to discontinue development of peramivir based on preliminary data from a phase III trial. The placebo-controlled trial was designed to evaluate peramivir in the treatment of acute influenza A and influenza B infections in otherwise healthy adults. A total of 1,246 subjects were randomized to one of three treatment groups over four flu seasons; 694 subjects were evaluable based on the presence of laboratory-confirmed influenza virus infection. No statistically significant difference was observed between peramivir- and placebo-treated groups in the primary efficacy endpoint - length of time from the first dose to the onset of clinically significant relief of influenza symptoms.

June 10, 2002

Phase II trial results suggest that Theratechnologies' ThGRF has a positive effect on cell-mediated immune response. The double-blind, multicenter trial evaluated the efficacy of ThGRF on the immune response to influenza vaccination. The trial included 87 subjects with an average age of 74.6 years. Subjects were randomized to receive daily treatment with 1.0 mg ThGRF, 2.0 mg ThGRF or placebo for four weeks before and four weeks after influenza vaccination. During the study period, the antigen-driven T lymphocyte proliferation response was statistically increased at the 2.0 mg dose (compared to placebo) for each of the three strains used in the vaccine. The response was also sustained following cessation of ThGRF treatment: the proliferation response was statistically higher in the 2.0 mg group when compared to the placebo group in the 8-20 week period.

This information does not represent a Lupus Research Institute endorsement of any listed study. It is merely a notice that the study is available. If you are presently under the care of a physician for lupus or other conditions, you should not disrupt your current program without discussing it with your doctor(s). Do not contact the Lupus Research Institute for information on these studies. Only contact the listed numbers. The Lupus Research Institute does not have any jurisdiction over or further involvement with these studies, other than to make people aware that they are being conducted.