Clinical Trials

Date: 2017-03-20

Type of information: Results

phase: 3

Announcement: results

Company: Nektar Therapeutics (USA - CA)

Product: NKTR-181

Action mechanism: mu-opioid agonist. NKTR-181 is a first-in-class, mu-opioid analgesic investigational drug candidate with a novel molecular structure designed to provide potent pain relief with a slow rate of entry into the brain. This slow rate of entry is designed to reduce the euphoria that can lead to the abuse of current opioid analgesics.

Disease: patients with chronic low back pain who are also opioid-naïve

Therapeutic area: CNS diseases

Country: USA

Trial details:

• The SUMMIT-07 Phase 3 trial utilizes an enriched-enrollment, randomized withdrawal (EERW) design and will enroll opioid-naïve patients ages 18 to 75 years who have had moderate to severe non-neuropathic chronic low back pain for at least six months. The study includes an open-label, dose titration period followed by a randomized, double-blind, placebo-controlled 12 week treatment period. During the open-label titration phase, study participants will be titrated on NKTR-181 tablets administered orally twice daily until they experience an adequate and sustained pain response. Patients who achieve this will then be randomized on a 1:1 basis to either continue to receive their analgesic dose of NKTR-181 or to receive placebo during the double-blind 12 week treatment period. A total of 208 patients will be randomized to each arm. No background NSAIDs are allowed throughout the study.
• The primary endpoint of the study is a change in pain as measured by the change in a patient\'s weekly pain score from baseline to week 12 of the randomized, double-blind treatment period.
• The SUMMIT Phase 3 program will also include a Phase 3 efficacy and safety trial in patients who are opioid-experienced (SUMMIT-12) as well as a 52-week long-term safety study (SUMMIT-LTS). (NCT02362672)

Latest news:

• • On March 20, 2017, Nektar Therapeutics announced positive results from the SUMMIT-07 Phase 3 efficacy study of NKTR-181, a first-in-class opioid analgesic.  The study compared twice-daily dosing of NKTR-181 tablets to placebo in the treatment of over 600 patients with moderate to severe chronic low back pain who were new to opioid therapy. The clinical trial met the primary efficacy endpoint of the study in demonstrating significantly improved chronic back pain relief with NKTR-181 compared to placebo (p=0.0019). Key secondary endpoints of the study were also met with high statistical significance.
• The study used an enriched-enrollment randomized withdrawal (EERW) trial design in patients with moderate to severe chronic low back pain. The trial included an open-label titration period in which patients were titrated to a tolerated, effective dose of NKTR-181 (100 mg to 400 mg twice-daily). Following this open-label titration period, patients entered a double-blind, placebo-controlled treatment period in which they were randomized 1:1 to either continue to receive the tolerated, effective dose of NKTR-181 or to receive matching placebo (i.e. active drug was withdrawn) for a period of 12 weeks.
• During the open-label titration period of the trial in which patients were titrated to a tolerated, effective dose of NKTR-181, average pain scores dropped by 65% (from 6.73 at screening to 2.32 at randomization, n=610).
• The primary endpoint of the study was mean change in the weekly average pain score in the double-blind randomized treatment period from baseline (end of open-label titration period) to week 12 (end of double-blind randomized treatment period).
• Primary and key sensitivity analyses:
• During the double-blind randomized treatment period of the trial, average pain scores increased more in the placebo arm versus NKTR-181 at week 12 from randomization baseline (1.46, placebo versus 0.92, NKTR-181, p=0.0019, n=610). 83% of patients completed the 12-week double-blind randomized treatment period and for these study completers, average pain scores increased more in the placebo arm versus NKTR-181 at week 12 from baseline (1.25, placebo versus 0.56, NKTR-181, p < 0.0001, n=504).
• Key secondary endpoints:
• A statistically significant proportion of patients on NKTR-181 experienced pain reductions greater than 30% compared to placebo (71.2% versus 57.1%; p=0.0003). A statistically significant proportion of patients on NKTR-181 experienced pain reductions greater than 50% compared to placebo (51.1% versus 37.9%; p=0.001). A statistically significant proportion of patients on NKTR-181 reported their general overall status and quality of life as "improved" or "very much improved" compared to placebo as assessed by the Patient's Global Impression of Change (PGIC) of pain medication questionnaire (51.5% versus 33.2%; p < 0.0001).
• The study also demonstrated that NKTR-181 had a favorable safety profile and was well tolerated. During the double-blind randomized treatment period, the most commonly reported adverse events for patients ( > 5%) were nausea (10.4%) and constipation (8.7%) in the NKTR-181 arm as compared to nausea (6.0%) and constipation (3.0%) in the placebo arm.
• Patients randomized to NKTR-181 as compared to placebo reported more favorable sleep outcomes as measured by the validated Medical Outcomes Study (MOS) Sleep Scale, which captures debilitating aspects of sleep most strongly associated with chronic pain. Patients reported better overall quality of sleep with less sleep problems on NKTR-181 versus placebo. There were no differences in daytime sleepiness on NKTR-181 versus placebo.
• Full data from the SUMMIT-07 study will be presented at a medical meeting in the second half of 2017.
• • On February 25, 2015, Nektar Therapeutics announced the enrollment of the first patient in SUMMIT-07, its initial Phase 3 study of NKTR-181, a first-in-class, opioid analgesic molecule with a slow rate of entry into the brain. This slow rate of entry is designed to reduce the euphoria that can lead to the abuse of current opioid analgesics. SUMMIT-07 will evaluate the efficacy, safety and tolerability of NKTR-181 in patients with chronic low back pain who are also opioid-naïve (new to treatment).NKTR-181 has been granted has been granted Fast Track designation for the treatment of moderate to severe chronic pain by the FDA.

Is general: Yes