Clinical Trials

Date: 2017-03-21

Type of information: Interim results

phase: 2

Announcement:

Company: Cellceutix (USA - MA), now Innovation Pharmaceuticals (USA - MA)

Product: brilacidin

Action mechanism:

• antibiotic. Brilacidin is the first of a new class of antibiotics called defensin-mimetics. Modeled after the body’s innate host-defense response, it penetrates bacterial cell wall membranes. Brilacidin also functions in an immunomodulatory capacity, lessening inflammation and promoting healing.

Disease: ulcerative proctitis/ulcerative proctosigmoiditis

Therapeutic area: Inflammatory diseases

Country:

Trial details:

• • CTIX-BRI-206 is a Phase 2a open-label, dose-escalation study, evaluating the efficacy, safety and pharmacokinetics (PK) of 3 dosing regimens of brilacidin—50 mg (Cohort A), 100 mg (Cohort B) and 200 mg (Cohort C)—in patients with active mild-to-moderate UP/UPS. Brilacidin is given daily as a retention enema across 42 consecutive days (6 weeks) of treatment. Endoscopic evaluation (photos and videos) of rectum and mucosa up to 40 cm from the anal verge in patients is performed at Screening and at End of Treatment (Day 42).
• The primary objective of the P-o-C trial is to assess the frequency of clinical and endoscopic remission with brilacidin administered per rectum in subjects with active ulcerative proctitis or ulcerative proctosigmoiditis (UP/UPS) after 6 weeks of treatment. Secondary objectives include evaluation of safety and tolerability of brilacidin when administered per rectum, evaluation of clinical remission at Week 2 and Week 4, assessment of systemic exposure and/or pharmacokinetics of Brilacidin when administered per rectum, assessment of the efficiency of brilacidin by biomarker evaluation of biopsy samples for interleukin (IL)-6 and IL-1beta, and estimation of statistical power for subsequent trial(s) in UP and UPS.
• •

Latest news:

• • On March 21, 2017, Cellceutix announced additional favorable topline findings as part of interim analysis from its ongoing Phase 2a Proof-of-Concept (PoC) study of brilacidin for the treatment of ulcerative proctitis/ulcerative proctosigmoiditis. Presented below is information on Cellceutix’s study of Brilacidin in UP/UPS, including detailed trial results observed through the first two cohorts (12 patients). Three of six patients in the third and final cohort have been enrolled this week and the Company anticipates the full study will be completed in 2Q2017. After 6 weeks (42 days) of daily treatment with Brilacidin all 12 patients from the first two cohorts experienced a beneficial response as measured by MMDAI scoring parameters.

• Primary Efficacy Endpoint of Clinical Remission (accounting for Stool Frequency, Rectal Bleeding and Endoscopy Findings subscores)—50 percent of patients in Cohort A (3 of 6) and 50 percent of patients in Cohort B (3 of 6) met this endpoint; all 6 of the remaining patients in Cohorts A and B met 2 of the 3 criteria (Partial Response).

• Full MMDAI (accounting for Stool Frequency, Rectal Bleeding, Physician’s Global Assessment and Endoscopy Findings subscores)—notable improvements observed in 10 of 11 patients (one patient declined endoscopy at end of treatment):

• - 100 percent reduction in 2 patients in Cohort A and 2 patients in Cohort B

• - 50-75 percent reduction in 2 patients in Cohort A and 4 patients in Cohort B

• - 20 percent reduction in 1 patient in Cohort A

  Partial MMDAI (accounting for Stool Frequency, Rectal Bleeding and Physician’s Global Assessment subscores)—notable improvements observed in 11 of 12 patients: - 100 percent reduction in 3 patients in Cohort A and 3 patients in Cohort B -  50-83 percent reduction in 2 patients in Cohort A and 3 patients in Cohort B - 0 percent reduction in 1 patient in Cohort A
• Patient Quality of Life (as assessed by the Short Inflammatory Bowel Disease Questionnaire, SIBDQ)—notable improvements in all 12 patients; 50 percent of patients in Cohort A (3 of 6) and 80 percent of patients in Cohort B (5 of 6) reported significant improvements of 15 points to more than 50 points higher on the 70-point SIBDQ scale.
• Other Clinically Meaningful Observations
• -  Endoscopy subscore of ? 1 met in 7 of 11 patients (1 patient declined final endoscopy). -  PGA subscore improved for 10 of 12 patients. - Rectal Bleeding subscore improved for all 12 patients. - Stool Frequency subscore demonstrated improvement by study end for all patients who were abnormal at study start.Brilacidin was generally well-tolerated with No Serious Adverse Events (SAEs). All 16 Adverse Events (AEs) experienced by a total of 6 patients were rated by Investigators as “Unlikely Related” or “Not Related” to treatment.
• • On March 8, 2017,  Cellceutix announced interim results in the first two cohorts of its ongoing Phase 2a clinical trial of Brilacidin for the induction of remission of mild-to-moderate ulcerative colitis. All twelve (12) patients across the first two cohorts have completed their full dosing schedules in the study. Comparison to baseline after six weeks of treatment showed:
  • All 12 patients experienced a beneficial response, as measured by the Modified Mayo Disease Activity Index (MMDAI).
    • At Day 42, the Primary Efficacy Endpoint of Clinical Remission (accounting for Stool Frequency, Rectal Bleeding, and Endoscopy sub-scores) was met in half (n=6) of all patients (3 of 6 in Cohort A; 3 of 6 in Cohort B).
    • Among the remaining patients (n=6) in Cohorts A and B not meeting all three criteria for Clinical Remission, two of the three criteria were achieved by all of these patients (defined as a Partial Response).
  Measurements of drug concentrations in plasma continued to show limited systemic absorption of Brilacidin, with all values registering less than 100 ng/mL for all six patients in Cohort A and averaging approximately 200 ng/mL maximum concentrations across the six patients in Cohort B.
• Patients for Cohort C (200 mg, the highest and final dosing group) are now being enrolled. Further detailed analyses, across all three cohorts once the trial is completed, will establish which dosing level provides the most favorable overall outcomes.• On February 22, 2017, Cellceutix announced progression of its ongoing phase 2 clinical trial of brilacidin to the third cohort (highest dose) for induction of remission of mild-to-moderate ulcerative colitis after satisfactory safety of prior cohorts was reported by the study’s Safety Committee. Patients included those with Ulcerative Proctitis/Ulcerative Proctosigmoiditis (UP/UPS), two types of Inflammatory Bowel Disease (IBD).
• • On January 17, 2017, Cellceutix announced that enrollment has been completed in the second cohort of the phase 2 open label proof-of-concept trial evaluating brilacidin for mild-to-moderate ulcerative proctitis/ulcerative proctosigmoiditis.
• • On December 7, 2016, Cellceutix announced initiation of the second cohort of patients treated with brilacidin for ulcerative proctitis/ulcerative proctosigmoiditis .
• • On October 10, 2016,  Cellceutix announced interim results observed for the first four patients treated with brilacidin for ulcerative proctitis/ulcerative proctosigmoiditis (UP/UPS). Four (4) of 6 patients to date in the lowest dosing cohort (50 mg) have completed the study. Comparison to baseline after 6 weeks of treatment showed:
• All 4 patients experienced a clinically meaningful response, as measured by the Modified Mayo Disease Activity Index (MMDAI).
• At Day 42, on the Partial MMDAI (accounting for Stool Frequency, Rectal Bleeding, and Physician’s Global Assessment scores), 2 of 4 patients achieved full response (100% reduction) and the other 2 patients had notable improvement (50% reduction).
• At Day 42, on the MMDAI (equivalent to Partial MMDAI + Endoscopy score; completed by 3 of 4 patients), 1 of 3 patients achieved full response (100% reduction) and 2 of 3 patients had notable improvement (50% reduction). One patient who had demonstrated a full response on the Partial MMDAI (as defined in first bullet point) did not consent to the final endoscopy, so their data cannot be included in these initial results.
• At Day 42, on the Partial MMDAI (accounting for Stool Frequency, Rectal Bleeding, and Physician’s Global Assessment scores), 2 of 4 patients achieved full response (100% reduction) and the other 2 patients had notable improvement (50% reduction).
• At Day 42, on the MMDAI (equivalent to Partial MMDAI + Endoscopy score; completed by 3 of 4 patients), 1 of 3 patients achieved full response (100% reduction) and 2 of 3 patients had notable improvement (50% reduction). One patient who had demonstrated a full response on the Partial MMDAI (as defined in first bullet point) did not consent to the final endoscopy, so their data cannot be included in these initial results.
• Patient quality of life, as assessed by the Short Inflammatory Bowel Disease Questionnaire (SIBDQ), was improved after 6-weeks of treatment with brilacidin. Brilacidin was generally well-tolerated and patients maintained stable normal vital signs during treatment. For all 4 patients, measurements of drug concentrations in plasma showed all levels, across all time points, to be below the lower limit of quantification (i.e., <100 ng/mL), which is consistent with very limited systemic exposure from administration per rectum by enema. In comparison, based on a previously completed and successful Phase 2b clinical trial of Brilacidin in the treatment of serious skin infections, maximum concentrations of the drug in plasma administered by intravenous (iv) dosing, ­­at 0.6 mg/kg and 0.8 mg/kg, were approximately 9,000 ng/mL and 12,000 ng/mL, respectively.
• • On July 18, 2016, Cellceutix provided additional information in the ongoing, open-label Phase 2 Proof-of-Concept (P-o-C) trial of brilacidin for the treatment of ulcerative proctitis or ulcerative proctosigmoiditis. Brilacidin is being evaluated in adults with active, mild to moderate UP or UPS present for at least three months prior to screening with disease extending at least five centimeters, but no further than 40 centimeters from the anal verge, as confirmed by sigmoidoscopic examination.
• Cellceutix has been advised that the first patient in Cohort A remains on study. The clinical site administering Brilacidin to this patient has informed the Company, “Both the patient and the site staff have been amazed how the study drug works as all the symptoms decreased significantly within the 1st week of treatment.”
• While impressed and optimistic about the initial feedback, Cellceutix needs to strongly caution that this is limited feedback from only the first patient in the trial and the initial results may not be durable for the patient or indicative of future outcomes in the study.
• • On June 15, 2016, Cellceutix announced that patients have been screened and the administration of brilacidin to patients is expected to begin this week in the Phase 2 Proof of Concept trial of brilacidin for the treatment of ulcerative proctitis.
• Given its robust anti-inflammatory properties, brilacidin offers patients a promising non-corticosteroid alternative to current clinical treatments. Long-term use of rectal corticosteroids should be avoided, as it can produce potentially serious side effects.
• Designed as a Proof of Concept trial based on considerable pre-clinical work, the study's primary goal is the remission of the condition. A successful Proof of Concept ulcerative proctitis trial would be a key step in advancing the Brilacidin franchise into other inflammatory bowel diseases. The trial is being conducted in an overseas hospital/clinic setting with brilacidin being administered with water in an enema. A foam formulation of brilacidin for use in further studies is in development.
• • On March 30, 2016, Cellceutix announced that the company has received initial approval for the planned Proof of Concept, Phase 2, clinical trial of brilacidin for ulcerative proctitis. The local ethics committee, responsible for oversight and allowance of the trial, granted this approval, so the trial can now move forward.
• Cellceutix is now awaiting the country’s Ministry of Health permission so it may begin exporting brilacidin into the country and directly to the clinical sites. The location of the trial isn’t currently being disclosed for competitive reasons.
• This clinical trial is the third indication for brilacidin.

Is general: Yes