Clinical Trials

Date: 2017-05-19

Type of information: Publication of results in a medical journal

phase: 2

Announcement: publication of results in Biotechnology Reports

Company: Soligenix (USA - NJ)

Product: dusquetide (SGX942)

Action mechanism:

•  peptide. SGX942 is a fully synthetic, 5-amino acid peptide with high aqueous solubility and stability. This peptide is an Innate Defense Regulator (IDR), a new class of short, synthetic peptides that has a novel mechanism of action in that it has simultaneous anti-inflammatory and anti-infective activity. IDRs have no direct antibiotic activity but modulate host responses, increasing survival after infections with a broad range of bacterial Gram-negative and Gram-positive pathogens, as well as accelerating resolution of tissue damage following exposure to a variety of agents including bacterial pathogens, trauma and chemo- and/or radiation therapy.

Disease: oral mucositis in patients undergoing chemoradiation therapy for head and neck cancer

Therapeutic area: Cancer - Oncology

Country: USA

Trial details:

• This Phase 2 study is a randomized, double-blind, dose-ranging, placebo-controlled trial, initially set to enroll approximately 75 subjects across 3 SGX942 dose groups and a placebo group, focused on demonstrating the safety and biologic activity of SGX942 in patients with cancer of the mouth and oropharynx who often experience debilitating oral mucositis as a consequence of their treatment with CRT. Following the DRC review of available data on the subjects enrolled in the trial, the committee recommended that enrollment include at least an additional 20 subjects randomized into either a single SGX942 dose group or the placebo group to allow for a more targeted assessment of the drug's potential effect and to inform final dose selection in this patient population. The efficacy assessment is the comparison of the incidence and/or duration of both ulcerative and severe oral mucositis throughout the subjects' 7 week course of CRT and for an additional 4 weeks thereafter.  The Phase 2 exploratory study enrolled 111 patients across three SGX942 dose groups (i.e., 1.5, 3.0, and 6.0 mg/kg) and a placebo group and evaluated patients undergoing CRT for head and neck cancer.
• The Phase 2 oral mucositis clinical study was partially funded with a grant from the National Institute of Dental and Craniofacial Research Small Business Innovation Research grant #1R43 DE024032-01. (NCT02013050)

Latest news:

• • On May 18, 2017, Soligenix announced that long-term follow-up data from its recent positive Phase 2 clinical trial, in which SGX942 (dusquetide) demonstrated a significant reduction in the median duration of severe oral mucositis in patients with head and neck cancer, have been published in the peer-reviewed journal Biotechnology Reports. These 12-month data further support the safety and tolerability of SGX942, with the 1.5 mg/kg treatment group demonstrating accelerated tumor resolution and a decreased mortality rate relative to the placebo group. In a randomized, double-blind, placebo-controlled Phase 2 clinical trial in 111 patients, SGX942 (1.5 mg/kg dusquetide) successfully reduced the median duration of severe oral mucositis when compared to placebo by 50% in all patients, and by 67% in patients receiving the most aggressive chemoradiation therapy  for treatment of their head and neck cancer. In addition to the oral mucositis findings, decreases in the bacterial infection rate were observed with SGX942 treatment, along with an increased incidence of "complete response" of tumor at the one month follow-up visit and a reduction in opioid pain medication use. Long-term follow-up data indicate that the tumor resolution was enduring and, moreover, that the mortality rate in the SGX942 1.5 mg/kg treatment group was lower (p=0.08) than the placebo group over the 12 months following completion of CRT. These data further support the safety and tolerability of SGX942 in this patient population. Potential ancillary benefits of utilizing SGX942 for the treatment of oral mucositis include the reduction of infection, the accelerated tumor resolution and the decreased mortality rate. • On December 8, 2016, Soligenix announced the long-term follow-up data from its Phase 2 clinical trial with SGX942 (dusquetide) in oral mucositis in head and neck cancer patients undergoing chemoradiation therapy (CRT). The additional 12-month safety data remains consistent with the preliminary positive safety and efficacy findings from the Phase 2 study and provide further support for advancing SGX942 into a pivotal Phase 2b/3 clinical trial. Following the positive results announced in December 2015 (see below), in which SGX942 at a dose of 1.5 mg/kg, successfully reduced the median duration of severe OM by 50% in all patients and by 67% in patients at highest risk of developing severe OM, long-term follow-up visits conducted throughout 2016 further demonstrated that SGX942 was safe, well-tolerated, and did not interfere with CRT as demonstrated by improved survival and tumor resolution at one and 12 months. Overall, there were no drug-related toxicities identified in this study. While the placebo population experienced the expected 12-month survival rate of approximately 80%, as defined in the Surveillance, Epidemiology, and End Results (SEER) statistics 1975-2012 from the National Cancer Institute, the SGX942 1.5 mg/kg treatment group reported a 12-month survival rate of 93% (7% mortality in the SGX942 1.5 mg/kg group compared to 19% in the placebo group). Similarly, tumor resolution (complete response) at 12 months was better in the SGX942 1.5 mg/kg treatment group relative to the placebo population (80% in the 1.5 mg/kg group compared to 74% in the placebo group). In addition to safety, evaluations of other secondary efficacy endpoints, such as the utilization of opioid pain medication, indicated that the SGX942 1.5 mg/kg treatment group had a 40% decrease in the use of opioids at the later stage of the treatment phase of the trial, when OM is usually most severe and expected to increase pain medication use. This was in contrast to the placebo group, which demonstrated a 10% increase in use of opioids over this same period. These results are consistent with the observed significant decrease in the duration of severe OM. There were no differences observed in the rates of xerostomia (dry mouth) and trismus (limited jaw range of motion) across the SGX942 and placebo dose groups in the study.
• This study achieved all objectives, including identifying the best dose of 1.5 mg/kg. In the 1.5 mg/kg treatment group, the median duration of severe OM was decreased by 50%, from 18 days to 9 days (p=0.099), meeting the prospectively defined statistical threshold of p<0.1 in the study protocol. Further, patients receiving the most aggressive CRT in this dose group had even more striking reductions in their median duration of severe OM of 67%, from 30 days to 10 days (p=0.040). Clinicians are most concerned about severe OM, which includes patients who cannot eat and/or drink due to their mouth ulcers. All dose levels of SGX942 were found to be safe and well tolerated. In addition to the OM findings and safety assessments, a decrease in infection rate was also observed with SGX942 treatment, particularly with infections of bacterial origin. Top-line data from this study was recently published in  the Journal of Biotechnology. The long-term (12 month) follow-up data from the trial is also expected to be submitted for future presentation and publication.Soligenix is now engaging the FDA  and the European Medicines Agency (EMA) on the design of a pivotal Phase 2b/3 clinical program. The company is also looking to expand SGX942 potential utility in the infectious disease space.
• •  On October 18, 2016, Soligenix announced the publication of interim results from its recent Phase 2 clinical trial in which SGX942 (dusquetide) demonstrated a statistically significant reduction in the median duration of severe oral mucositis by 50% in all patients and by 67% in patients at the highest risk for developing severe oral mucositis. Other important findings in the study included a reduction in the incidence of infection and an increase in tumor resolution at one month post-radiation. The publication also delineates the supportive nonclinical data in this indication, demonstrating consistency in the qualitative and quantitative biological response, including dose response, across the nonclinical and clinical data sets. The results were published online in the Journal of Biotechnology. As a first-in-class innate defense regulator (IDR), dusquetide modulates the innate immune system by interacting at an intracellular integration point, operating downstream of most innate immune receptors and upstream of most cytokine and chemokine effectors. IDRs directly interact with an important protein known as p62, or sequestosome-1, thereby enhancing the tissue-healing and anti-infective mechanisms of the innate immune system and decreasing the often deleterious inflammatory responses. The pathogenesis of oral mucositis is believed to be related to a dysregulation of the innate immune system. In a randomized, double-blind, placebo-controlled Phase 2 clinical trial, SGX942, containing dusquetide at a dose of 1.5 mg/kg, successfully reduced the median duration of severe oral mucositis when compared to placebo by 50% in all patients and by 67% in patients receiving the most aggressive chemoradiation therapy for treatment of their head and neck cancer. In addition to the oral mucositis findings, decreases in the non-fungal (i.e., bacterial) infection rate were observed with SGX942 treatment (45% in placebo versus 28% in SGX942 at 1.5 mg/kg), along with an increased incidence of "complete response" of tumor (i.e., disappearance) at the one month follow-up visit (47% in placebo versus 63% in SGX942 at 1.5 mg/kg). Preclinical data supporting the anti-infective activity of dusquetide has also been previously published. The Phase 2 oral mucositis clinical study was partially funded with a grant from the National Institute of Dental and Craniofacial Research Small Business Innovation Research grant #1R43 DE024032-01. Long-term follow-up visits remain ongoing in the study with further data expected by the end of 2016.
• * On June 25, 2016,  Soligenix has presented preliminary results from its SGX942 Phase 2 clinical trial in oral mucositis  at the Multinational Association for Supportive Care in Cancer (MASCC) conference. The presentation is entitled "SGX942 reduces the duration of severe oral mucositis in head and neck cancer patients in a phase 2 placebo-controlled, double-blinded randomized trial".
• Preliminary data with SGX942 was announced on December 16, 2015 (see below). Long-term follow-up visits in the study are ongoing with final results expected by the end of the year. The trial, entitled "A Phase 2, double-blind, randomized, placebo-controlled, dose-escalating, multicenter study of SGX942 for the attenuation of oral mucositis in patients being treated with concomitant chemoradiation for the treatment of squamous cell carcinoma of the head and neck", was the first evaluation of dusquetide efficacy in a sick patient population and demonstrated a positive, clinically meaningful reduction in the duration of severe oral mucositis. This Phase 2 trial enrolled 111 patients treated twice per week during radiation therapy with a 4-minute IV infusion.  Compared to placebo patients, patients receiving 1.5 mg/kg of SGX942 had a 50% reduction in duration of severe oral mucositis (9 days versus 18 days) and a corresponding trend in reductions in incidence and AUC. In patients receiving aggressive cisplatin, SGX942 at 1.5 mg/kg decreased the duration of severe oral mucositis by 67% and ulcerative oral mucositis by 22%. Additionally, the number of patients with a “complete RECIST response” was increased at the initial follow-up visit from 39% to 47%. Reported infections were also decreased with SGX942, consistent with the nonclinical biology findings.The reduction in duration of severe oral mucositis ranged from 50% in the overall population to 67% in the population with the most severe disease. The incidence of infection and the resolution of tumor burden were also improved with dusquetide treatment.On the basis of these results, Soligenix is currently planning a pivotal Phase 2b/3 clinical program.
• • On December 16, 2015, Soligenix announced positive results in its Phase 2 clinical trial, in which SGX942, at a dose of 1.5 mg/kg, successfully reduced the median duration of severe oral mucositis by 50% in all patients and by 67% in patients receiving the most aggressive chemoradiation therapy (CRT) for treatment of their head and neck cancer. This exploratory study achieved all objectives, including identifying a best dose of 1.5 mg/kg. The study enrolled 111 patients across three SGX942 dose groups (i.e., 1.5, 3.0, and 6.0 mg/kg) and a placebo group and evaluated patients undergoing CRT for head and neck cancer. In the 1.5 mg/kg treatment group, the median duration of severe oral mucositis was decreased by 50%, from 18 days to 9 days (p=0.099). In addition to the oral mucositis findings, a trend towards increased incidence of “complete response” of tumor at the one month follow up visit was observed (47% in placebo vs. 63% in SGX942 at 1.5 mg/kg). Decreases in mortality and significant decreases in infection rate were also observed with SGX942 treatment and are being further evaluated. In the preliminary analysis, SGX942 was found to be generally safe and well tolerated, consistent with the safety profile observed in the prior Phase 1 study conducted in 84 healthy volunteers. Long-term follow-up evaluations are ongoing with final results expected in the fourth quarter of 2016. Data from this Phase 2 trial is expected to be submitted for future presentation and publication.
• • On August 31, 2015, Soligenix announced it has completed enrollment of the additional subjects, as directed by the Data Review Committee (DRC) earlier this year, into the company's Phase 2 study for SGX942.

 

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