History of NI-03
The TACTIC clinical study is investigating a drug compound, NI-03, a serine protease inhibitor that may potentially act in several ways to ease symptoms associated with chronic pancreatitis (CP) or prevent the further progression of the disease.
NI-03 has been approved in Japan since 1985 for the remission of acute symptoms of CP. It has also been used for the same indication in South Korea since 1989.
In nine open-label and three double-blind randomized parallel-group studies from Japan, NI-03 has been shown to relieve the symptoms associated with CP with minimal adverse events. However, several were non-comparative, uncontrolled studies and many responses were graded subjectively and not presented as objective findings. All three double-blind studies noted some level of improved efficacy of NI-03 vs placebo.
Additional Japanese studies have suggested that NI-03 may reduce the risk of developing diabetes. Subsequent post-marketing surveillance revealed no problems with efficacy or safety in the 30 years that NI-03 has been available.
These anecdotal findings are not robust enough to obtain U.S. Food and Drug Administration (FDA) approval, therefore the TACTIC study was designed to support regulatory approval of NI-03 in the US. The FDA has granted NI-03 with orphan drug status, provided to drugs and biologics that are intended for the safe and effective treatment, diagnosis, or prevention of rare diseases or disorders. In addition, FDA Fast Track Designation was granted to NI-03, which is intended to accelerate the marketing application review process. Fast Track Designation is given to drugs that treat serious conditions and are intended to fill an unmet medical need when a serious condition doesn’t have an approved treatment.
Current treatment landscape and unmet need
There are no currently approved medications in the United States for the relief of pain associated with CP. There are treatment guidelines on how to manage the symptoms of CP including lifestyle changes (abstaining from tobacco and alcohol, and adopting a low-fat diet), the three step analgesic ladder laid out by the World Health Organization (beginning with non-opioids, progressing to mild opioids, then strong opioids), and pancreatic enzymes replacement therapy. Non-medication options include nerve blocks, endoscopic therapy, and various surgical procedures; all of which provide no guarantee of pain relief.
It is common for patients to progress to opioid use to manage the pain associated with CP, however, there is a lack of evidence showing a long-term benefit of opioids in pain and function. Furthermore, there is extensive evidence regarding the harms associated with opioid use, including opioid misuse, overdose, and motor vehicle injury. With the opioid epidemic in the United States, it is crucial to find other treatments that are more effective at managing pain without the associated risks for long-term use.
A multidisciplinary approach with current treatments may ameliorate symptoms and improve patient outcomes, however, these treatments only provide temporary pain relief and manage complications, but are incapable of arresting or slowing the progression of this disease. Treatment failure or only partial success is common with the current medication options.
The TACTIC study is currently enrolling subjects for a phase 2, randomized, double- blind, parallel-group, dose-ranging study to evaluate the efficacy and safety of NI-03 compared to placebo in subjects with Chronic Pancreatitis, including PK assessments. All subjects will complete a five-week treatment period to one of four blinded treatments (placebo, 100 mg, 200 mg or 300 mg) self-administered TID.
Screening Period: A 7-day Run-In period will be conducted to establish subject baseline assessments of pain and to familiarize participants with the 11-point numeric rating scale (NRS). Safety lab assessments along with ECG, PE and other study related procedures will be performed to assess the study baseline.
Dosing Period: After Screening, subjects will be randomized to 1 of 4 treatment groups according to their level of the daily opiate use. Study drug will be self-administered three-times daily with food. At each visit, dosing compliance will be reviewed, safety assessments will be performed, and blood samples will be collected.
There will be two visits which require serial PK collection (6 time points over 6 hours). Subjects will be asked to remain at the clinic until all PK collection is completed.
Follow-Up Period: Subjects will have an End of Study (EOS) Visit for safety assessments. For subjects who discontinue early from the study, these assessments should be completed within 7 days of the subject receiving their last dose of study medication.
To learn more about the participating clinical sites & physicians, please see more details at Clinicaltrials.gov.
Primary & Secondary Objectives
The primary objective of the TACTIC study is to determine the efficacy, PK, and safety of three doses of NI-03 (100 mg, 200 mg, and 300 mg) as compared to placebo when administered three times daily (TID) in subjects with Chronic Pancreatitis.
Secondary objectives are to evaluate the safety of NI-03 compared to placebo in subjects with Chronic Pancreatitis and to compare the PK profiles of the three doses of NI-03 in this population. Using the PANQOLI and Brief Pain Inventory, the study will also examine the impact of NI-03 on the quality of life (QOL) of subjects with Chronic Pancreatitis.
During the TACTIC study, patients will have an initial clinic visit to establish eligibility, followed by 4 clinic visits over the next 5 weeks to ensure there are no unanticipated effects during the trial, and to assess efficacy. At each clinic visit at least one blood sample will be taken, and on two occasions patients will be asked to remain at the clinic for up to 5 hours to measure concentration of remains drug in the patient’s blood. Before receiving any study drug during the Double-Blind Phase and at pre-specified post-dose time points, vital signs will be measured, adverse events (AEs) and concomitant medication use will be queried, an ECG will be performed, blood and urine samples will be collected for clinical laboratory tests, urine pregnancy test (for female subjects of child-bearing potential) will be performed, blood samples will be collected for determination of PK parameters, and the BPI and PANQOLI will be completed. Subjects will return to the study clinic on Days 15, and 29 for completion of study assessments.
Key Eligibility Criteria
- Males or females aged 18-85 years of age
- Clinical diagnosis of Chronic Pancreatitis through EUS, CT, MRI, MRCP, ERCP which confirms the Rosemont and/or Cambridge criteria
- Experiencing an average, daily worst pain score of at least 4 on an 11-point scale (0 = No pain and 10= worst pain imaginable)
- On a non-opioid analgesic regimen that is expected to remain stable during the study period, or an opioid regimen with an oral morphine-equivalent dose of ≤ 100 mg daily
- Not pregnant, planning to become pregnant or breast feeding, and not have a positive serum or urine pregnancy test result during the study
- No current history of active heavy alcohol use (defined as more than 2 alcoholic drinks per day or 14 alcoholic drinks per week)
(Please contact our TACTIC clinical team for a comprehensive list of participant inclusion & exclusion requirements @ firstname.lastname@example.org. You may also access the participant pre-screener to find out if your patient might be eligible)
Current Study Data
The ongoing phase 2 trial-in-progress poster was presented at the annual meeting of the American Pancreatic Association (APA) 2019. Below is the poster that was presented.
Study Site Locations
TACTIC currently has clinical study sites enrolling participants, nationwide. If you may have eligible patients diagnosed with Chronic Pancreatitis or are interested in learning more about participating as a study site, please contact the TACTIC study team at email@example.com.