A Study to Evaluate the Efficacy and Safety of BLI5100 in Patients With Non-Erosive Reflux Disease

A Phase 3, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of BLI5100 in Patients With Non-Erosive Reflux Disease

The objective of the Treatment Phase of the study is to evaluate the safety and efficacy of 4 weeks of once daily oral administration of BLI5100 low dose, BLI5100 high dose, or placebo in patients with NERD. The objective of the Extension Phase of the study is to evaluate the safety of extended exposure to once daily oral administration of BLI5100 low dose and BLI5100 high dose in patients with NERD.

Study Overview

• Status: Completed
• Conditions: Non-erosive Reflux Disease
• Intervention / Treatment: Drug: BLI5100; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 800
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
      • Research Site 24
  • Arizona
    • Peoria, Arizona, United States, 85381
      • Research Site 132
    • Phoenix, Arizona, United States, 85018
      • Research Site 62
    • Tucson, Arizona, United States, 85712
      • Research Site 27
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Research Site 87
    • North Little Rock, Arkansas, United States, 72117
      • Research Site 117
  • California
    • Arcadia, California, United States, 91006
      • Research Site 51
    • Bakersfield, California, United States, 93309
      • Research Site 126
    • Bell Gardens, California, United States, 90201
      • Research Site 66
    • Canoga Park, California, United States, 91304
      • Research Site 19
    • Chula Vista, California, United States, 91910
      • Research Site 94
    • Huntington Park, California, United States, 90255
      • Research Site 10
    • La Mesa, California, United States, 91942
      • Research Site 55
    • Long Beach, California, United States, 90808
      • Research Site 120
    • Los Angeles, California, United States, 90017
      • Research Site 72
    • Los Angeles, California, United States, 90057
      • Research Site 54
    • Mission Viejo, California, United States, 92691
      • Research Site 18
    • San Diego, California, United States, 92120
      • Research Site 14
    • Santa Ana, California, United States, 92704
      • Research Site 13
    • Santa Ana, California, United States, 92703
      • Research Site 85
    • Santa Maria, California, United States, 93458
      • Research Site 41
  • Colorado
    • Aurora, Colorado, United States, 80012
      • Research Site 112
    • Littleton, Colorado, United States, 80120
      • Research Site 89
  • Florida
    • Boca Raton, Florida, United States, 33434
      • Research Site 74
    • Cooper City, Florida, United States, 33024
      • Research Site 108
    • Doral, Florida, United States, 33172
      • Research Site 91
    • Hialeah, Florida, United States, 33013
      • Research Site 03
    • Homestead, Florida, United States, 33030
      • Research Site 78
    • Lake City, Florida, United States, 32055
      • Research Site 09
    • Maitland, Florida, United States, 32751
      • Research Site 23
    • Miami, Florida, United States, 33136
      • Research Site 43
    • Miami, Florida, United States, 33134
      • Research Site 38
    • Miami, Florida, United States, 33142
      • Research Site 81
    • Miami, Florida, United States, 33155
      • Research Site 67
    • Miami, Florida, United States, 33173
      • Research Site 92
    • Miami, Florida, United States, 33185
      • Research Site 31
    • Miami, Florida, United States, 33186
      • Research Site 71
    • Miami Lakes, Florida, United States, 33014
      • Research Site 42
    • New Port Richey, Florida, United States, 34653
      • Research Site 17
    • Ocoee, Florida, United States, 34761
      • Research Site 90
    • Orlando, Florida, United States, 32807
      • Research Site 107
    • Palmetto Bay, Florida, United States, 33157
      • Research Site 05
    • Saint Petersburg, Florida, United States, 33709
      • Research Site 95
    • Sunrise, Florida, United States, 33351
      • Research Site 11
    • Viera, Florida, United States, 32940
      • Research Site 46
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Research Site 04
    • Sandy Springs, Georgia, United States, 30328
      • Research Site 59
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Research Site 101
  • Illinois
    • Downers Grove, Illinois, United States, 60515
      • Research Site 102
    • Gurnee, Illinois, United States, 60031
      • Research Site 01
    • Northbrook, Illinois, United States, 60062
      • Research Site 113
    • Oak Lawn, Illinois, United States, 60453
      • Research Site 02
  • Indiana
    • South Bend, Indiana, United States, 46635
      • Research Site 135
  • Louisiana
    • Covington, Louisiana, United States, 70433
      • Research Site 125
    • Houma, Louisiana, United States, 70363
      • Research Site 45
    • Marrero, Louisiana, United States, 70072
      • Research Site 12
    • Metairie, Louisiana, United States, 70006
      • Research Site 48
    • Metairie, Louisiana, United States, 70006
      • Research Site 124
    • New Orleans, Louisiana, United States, 70127
      • Research Site 34
    • West Monroe, Louisiana, United States, 71291
      • Research Site 25
  • Michigan
    • Chesterfield, Michigan, United States, 48047
      • Research Site 93
  • Missouri
    • Chesterfield, Missouri, United States, 63005
      • Research Site 111
    • Columbia, Missouri, United States, 65201
      • Research Site 137
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Research Site 06
    • Las Vegas, Nevada, United States, 89109
      • Research Site 73
    • Las Vegas, Nevada, United States, 89128
      • Research Site 127
    • Reno, Nevada, United States, 89511
      • Research Site 64
  • New Jersey
    • Englewood, New Jersey, United States, 07631
      • Research Site 129
    • Freehold, New Jersey, United States, 07728
      • Research Site 130
    • Jackson, New Jersey, United States, 08527
      • Research Site 131
  • New York
    • Brooklyn, New York, United States, 11235
      • Research Site 35
    • Great Neck, New York, United States, 11023
      • Research Site 07
    • Hartsdale, New York, United States, 10530
      • Research Site 28
    • New York, New York, United States, 10021
      • Research Site 58
    • New York, New York, United States, 10033
      • Research Site 49
    • Rochester, New York, United States, 14609
      • Research Site 40
  • North Carolina
    • Fayetteville, North Carolina, United States, 28304
      • Research Site 75
    • Mount Airy, North Carolina, United States, 27030
      • Research Site 69
    • Salisbury, North Carolina, United States, 28144
      • Research Site 116
  • Ohio
    • Columbus, Ohio, United States, 43213
      • Research Site 20
    • Columbus, Ohio, United States, 43215
      • Research Site 88
    • Mentor, Ohio, United States, 44060
      • Research Site 109
    • Springboro, Ohio, United States, 45066
      • Research Site 118
    • Westlake, Ohio, United States, 44145
      • Research Site 110
  • South Carolina
    • North Charleston, South Carolina, United States, 29405
      • Research Site 61
  • Tennessee
    • Hermitage, Tennessee, United States, 37076
      • Research Site 128
    • Kingsport, Tennessee, United States, 37663
      • Research Site 114
    • Nashville, Tennessee, United States, 37203
      • Research Site 60
    • Nashville, Tennessee, United States, 37211
      • Research Site 103
    • Shelbyville, Tennessee, United States, 37160
      • Research Site 50
  • Texas
    • Beaumont, Texas, United States, 77701
      • Research Site 115
    • Bellaire, Texas, United States, 77401
      • Research Site 100
    • Dallas, Texas, United States, 75230
      • Research Site 98
    • Forney, Texas, United States, 75126
      • Research Site 99
    • Katy, Texas, United States, 77494
      • Research Site 68
    • Lewisville, Texas, United States, 75057
      • Research Site 29
    • Pearland, Texas, United States, 77584
      • Research Site 32
    • Red Oak, Texas, United States, 75154
      • Research Site 30
    • San Antonio, Texas, United States, 78209
      • Research Site 22
    • San Antonio, Texas, United States, 78229
      • Research Site 26
    • San Antonio, Texas, United States, 78249
      • Research Site 21
    • Tomball, Texas, United States, 77375
      • Research Site 80
    • Waco, Texas, United States, 76710
      • Research Site 134
    • Wichita Falls, Texas, United States, 76301
      • Research Site 121
  • Utah
    • Ogden, Utah, United States, 84403
      • Research Site 105
    • Salt Lake City, Utah, United States, 84107
      • Research Site 57
    • Salt Lake City, Utah, United States, 84124
      • Research Site 106
    • Sandy, Utah, United States, 84092
      • Research Site 65
    • South Ogden, Utah, United States, 84405
      • Research Site 16
  • Virginia
    • Chesapeake, Virginia, United States, 23320
      • Research Site 77
    • Richmond, Virginia, United States, 23236
      • Research Site 136
  • West Virginia
    • Morgantown, West Virginia, United States, 26505
      • Research Site 97

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged ≥18 years at the time of signing informed consent;
2. Have experienced heartburn (burning sensation, pain at posterior bony thorax) for at least 6 months prior to Screening;
3. Have documented history of symptomatic GERD;
4. Have no mucosal break(s) on the upper GI endoscopy performed during Screening;
5. Have reported heartburn on ≥4 days during any consecutive 7-day period of the Screening Period as recorded in the eDiary;
6. Able to understand and comply with the protocol requirements;
7. Willing and able to provide written informed consent at Screening;
8. A female of reproductive potential defined as a non-post-menopausal female who has not had a bilateral oophorectomy or medically documented ovarian failure; or If a female of childbearing potential, agrees to use an acceptable form of birth control and avoid egg donation from the Screening Visit until 6 months after the last dose of study drug.
9. If a male, agrees to use an acceptable form of birth control from the Screening Visit until 3 months after the last dose of study drug.
10. If a male, agrees to abstain from sperm donation through 3 months after administration of the last dose of study drug.

Exclusion Criteria:

1. Unable to undergo an upper GI endoscopy;

2. Presence of esophageal stricture, gastroesophageal varix (including post sclerotherapy or ligation), untreated Barrett's esophagus, gastric bleeding, infection, tumor, or gastric or duodenal ulcer on the upper GI endoscopy;

   o Note: Patients with diagnosis of Schatzki's ring (mucosal tissue ring around lower esophageal sphincter) are eligible to participate.

3. Diagnosed with erosive gastroesophageal reflux disease, acute upper GI bleeding, gastric ulcer or duodenal ulcer, or acute gastritis within 2 months prior to the upper GI endoscopy;
4. Alarm symptoms such as odynophagia, severe dysphagia, upper GI bleeding, weight loss, anemia, or hematochezia within 4 weeks prior to Screening, unless the presumed malignancy is ruled out;

5. History or suspicion of functional upper gastrointestinal disorders, such as:

   • Functional heartburn, as described in the Rome IV criteria, or
   • Functional dyspepsia, as described in the Rome IV criteria.
6. History of a connective tissue disorder associated with GI symptoms (eg, scleroderma or systemic lupus erythematous) or inflammatory bowel disease, or documented history of delayed gastric emptying;

7. History of acid-suppressive, esophageal, or gastric surgery;

   o Note: This is not applicable to appendectomy, cholecystectomy, or endoscopic excision of benign tumor.

8. History of malignancy within the past 5 years (with the exception of resected basal cell or squamous cell carcinoma of the skin);

   o Note: This is not applicable to patients who had complete response or pathological complete response and whose tumor had not recurred for at least 5 years from the date of last treatment, or patients whose tumor had been removed by endoscopic resection without any findings indicating recurrence of the tumor within 3 years.

9. History of an allergic disease, or hypersensitivity or intolerance to the active ingredient or excipients of the study drug;

10. History of alcoholism, chronic opiate use, or substance addiction in the 12 months before Screening or a positive urine drug screen for opiates or substances of abuse;

    • Note: Patients on prescribed opioids are eligible to participate if they have been on a stable dose for >3 months prior to Screening.
    • Note: Retesting of a positive urine drug screen requires Medical Monitor approval. Positive urine drug screen for all drugs will require verification of prescription for the positive tested substance.

11. Presence of manic-depression, anxiety disorder, panic disorder, somatoform disorder, personality disorder, or other psychological disorder;

    o Note: A diagnosis of manic-depression, anxiety disorder, panic disorder, somatoform disorder, personality disorder, or other psychological disorder is not exclusionary, as long as the patient is asymptomatic and well-controlled on stable treatment (ie, stable dose for >6 months prior to Screening), including non-medical therapy.

12. Current use of antipsychotics, antidepressants, anxiolytics, or prescription sleeping medications, with the exception of a stable dose for >6 months prior to Screening;
13. Use of any gastric acid-suppressive agents, including PPIs, within 2 weeks prior to the upper GI endoscopy at Screening;
14. Use of 2 or more commercial doses of reflux esophagitis-related medications (including H2 blockers, prostaglandins, mucosal protective agents, prokinetics, and antacids) within 1 week prior to the upper GI endoscopy at Screening;

15. Requirement of persistent (>3 times per week for >30 days) use of non-steroidal anti-inflammatory drugs (NSAIDs) during the course of the study;

    o Note: Low-dose (≤100 mg/day) aspirin is allowed provided that it has been used for prophylaxis prior to study participation.

16. If a female, is pregnant, breastfeeding, or planning to become pregnant during the study or within 6 months after the last dose of study drug;
17. Positive test result for human immunodeficiency virus, hepatitis B surface antigen, or hepatitis C virus at Screening;

18. Positive test result for H. pylori at Screening or diagnosis and treatment of H. pylori within 4 to 6 weeks prior to Randomization;

    o Note: Patients who test positive for H. pylori at Screening will be offered treatment according to local standard of care and may be re-screened for eligibility following completion of treatment.

19. Abnormal laboratory results with clinical relevance at Screening as follows:

    • Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase level of ≥2 × upper limit of normal (ULN);
    • Total bilirubin level of ≥2 × ULN, unless Gilbert's syndrome is confirmed when direct bilirubin is ≤0.3 mg/dL;
    • Estimated glomerular filtration rate <30 mL/min; or
    • Serum magnesium <lower limit of normal.
20. Abnormal ECG of clinical significance (eg, major arrhythmia, multifocal premature ventricular contractions, or 2° atrioventricular block anomaly);
21. Presence of any gastric acid hypersecretory conditions, such as Zollinger-Ellison syndrome;
22. Involvement in another clinical study within 4 weeks of initiation of study drug; or
23. Any other clinically relevant condition that would confound study endpoints or adversely affect patient compliance with the study procedures in the medical judgment of the Investigator or Medical Monitor based on previous medical history or findings on Screening assessments .

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BLI5100 Low Dose; During the Treatment Period, patients will take BLI5100 low dose once daily, orally, for 8 weeks. During the Extension Period, patients will continue to take BLI5100 low dose once daily, orally, for 20 weeks.	Drug: BLI5100; Orally via tablet
Experimental: BLI5100 High Dose; During the Treatment Period, patients will take BLI5100 high dose once daily, orally, for 8 weeks. During the Extension Period, patients will continue to take BLI5100 high dose once daily, orally, for 20 weeks.	Drug: BLI5100; Orally via tablet
Placebo Comparator: Placebo; During the Treatment Period, patients will take placebo once daily, orally, for 8 weeks. In the Extension Phase, patients who received placebo in the Treatment Phase will be re-randomized to receive either BLI5100 low dose or BLI5100 high dose to take once daily, orally, for 20 weeks.	Drug: Placebo; Orally via tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of 24-hour heartburn-free days	4 Weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of patients with complete resolution of main symptoms (heartburn and regurgitation)	4 Weeks

Collaborators and Investigators

• Sponsor: Braintree Laboratories
• Investigators: Study Director: Leah Hollins, Braintree Laboratories / Sebela Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): September 6, 2022
• Primary Completion (Actual): October 13, 2023
• Study Completion (Actual): April 23, 2024

Study Registration Dates

• First Submitted: October 17, 2022
• First Submitted That Met QC Criteria: October 17, 2022
• First Posted (Actual): October 20, 2022

Study Record Updates

• Last Update Posted (Actual): July 24, 2024
• Last Update Submitted That Met QC Criteria: July 23, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastroesophageal Reflux; Non-Erosive Reflux Disease
• Other Study ID Numbers: BLI5100-302

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No