Clinical trial NCT05587322: A Study to Evaluate the Efficacy and Safety of BLI5100 in Patients With Non-Erosive Reflux Disease
Official title: A Phase 3, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of BLI5100 in Patients With Non-Erosive Reflux Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non-erosive Reflux Disease
Lead sponsor: Braintree Laboratories
Sponsor class: INDUSTRY
First posted: 2022-10-20
Enrollment: 800
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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 .

Primary outcomes:
measure: Percentage of 24-hour heartburn-free days
timeFrame: 4 Weeks
Secondary outcomes:
measure: Percentage of patients with complete resolution of main symptoms (heartburn and regurgitation)
timeFrame: 4 Weeks
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Research Site 24
state: Alabama
city: Peoria
country: United States
facility: Research Site 132
state: Arizona
city: Phoenix
country: United States
facility: Research Site 62
state: Arizona
city: Tucson
country: United States
facility: Research Site 27
state: Arizona
city: Little Rock
country: United States
facility: Research Site 87
state: Arkansas
city: North Little Rock
country: United States
facility: Research Site 117
state: Arkansas
city: Arcadia
country: United States
facility: Research Site 51
state: California
city: Bakersfield
country: United States
facility: Research Site 126
state: California
city: Bell Gardens
country: United States
facility: Research Site 66
state: California
city: Canoga Park
country: United States
facility: Research Site 19
state: California
city: Chula Vista
country: United States
facility: Research Site 94
state: California
city: Huntington Park
country: United States
facility: Research Site 10
state: California
city: La Mesa
country: United States
facility: Research Site 55
state: California
city: Long Beach
country: United States
facility: Research Site 120
state: California
city: Los Angeles
country: United States
facility: Research Site 72
state: California
city: Los Angeles
country: United States
facility: Research Site 54
state: California
city: Mission Viejo
country: United States
facility: Research Site 18
state: California
city: San Diego
country: United States
facility: Research Site 14
state: California
city: Santa Ana
country: United States
facility: Research Site 85
state: California
city: Santa Ana
country: United States
facility: Research Site 13
state: California
city: Santa Maria
country: United States
facility: Research Site 41
state: California
city: Aurora
country: United States
facility: Research Site 112
state: Colorado
city: Littleton
country: United States
facility: Research Site 89
state: Colorado
city: Boca Raton
country: United States
facility: Research Site 74
state: Florida
city: Cooper City
country: United States
facility: Research Site 108
state: Florida
city: Doral
country: United States
facility: Research Site 91
state: Florida
city: Hialeah
country: United States
facility: Research Site 03
state: Florida
city: Homestead
country: United States
facility: Research Site 78
state: Florida
city: Lake City
country: United States
facility: Research Site 09
state: Florida
city: Maitland
country: United States
facility: Research Site 23
state: Florida
city: Miami Lakes
country: United States
facility: Research Site 42
state: Florida
city: Miami
country: United States
facility: Research Site 38
state: Florida
city: Miami
country: United States
facility: Research Site 43
state: Florida
city: Miami
country: United States
facility: Research Site 81
state: Florida
city: Miami
country: United States
facility: Research Site 67
state: Florida
city: Miami
country: United States
facility: Research Site 92
state: Florida
city: Miami
country: United States
facility: Research Site 31
state: Florida
city: Miami
country: United States
facility: Research Site 71
state: Florida
city: New Port Richey
country: United States
facility: Research Site 17
state: Florida
city: Ocoee
country: United States
facility: Research Site 90
state: Florida
city: Orlando
country: United States
facility: Research Site 107
state: Florida
city: Palmetto Bay
country: United States
facility: Research Site 05
state: Florida
city: Saint Petersburg
country: United States
facility: Research Site 95
state: Florida
city: Sunrise
country: United States
facility: Research Site 11
state: Florida
city: Viera
country: United States
facility: Research Site 46
state: Florida
city: Marietta
country: United States
facility: Research Site 04
state: Georgia
city: Sandy Springs
country: United States
facility: Research Site 59
state: Georgia
city: Idaho Falls
country: United States
facility: Research Site 101
state: Idaho
city: Downers Grove
country: United States
facility: Research Site 102
state: Illinois
city: Gurnee
country: United States
facility: Research Site 01
state: Illinois
city: Northbrook
country: United States
facility: Research Site 113
state: Illinois
city: Oak Lawn
country: United States
facility: Research Site 02
state: Illinois
city: South Bend
country: United States
facility: Research Site 135
state: Indiana
city: Covington
country: United States
facility: Research Site 125
state: Louisiana
city: Houma
country: United States
facility: Research Site 45
state: Louisiana
city: Marrero
country: United States
facility: Research Site 12
state: Louisiana
city: Metairie
country: United States
facility: Research Site 124
state: Louisiana
city: Metairie
country: United States
facility: Research Site 48
state: Louisiana
city: New Orleans
country: United States
facility: Research Site 34
state: Louisiana
city: West Monroe
country: United States
facility: Research Site 25
state: Louisiana
city: Chesterfield
country: United States
facility: Research Site 93
state: Michigan
city: Chesterfield
country: United States
facility: Research Site 111
state: Missouri
city: Columbia
country: United States
facility: Research Site 137
state: Missouri
city: Las Vegas
country: United States
facility: Research Site 06
state: Nevada
city: Las Vegas
country: United States
facility: Research Site 73
state: Nevada
city: Las Vegas
country: United States
facility: Research Site 127
state: Nevada
city: Reno
country: United States
facility: Research Site 64
state: Nevada
city: Englewood
country: United States
facility: Research Site 129
state: New Jersey
city: Freehold
country: United States
facility: Research Site 130
state: New Jersey
city: Jackson
country: United States
facility: Research Site 131
state: New Jersey
city: Brooklyn
country: United States
facility: Research Site 35
state: New York
city: Great Neck
country: United States
facility: Research Site 07
state: New York
city: Hartsdale
country: United States
facility: Research Site 28
state: New York
city: New York
country: United States
facility: Research Site 58
state: New York
city: New York
country: United States
facility: Research Site 49
state: New York
city: Rochester
country: United States
facility: Research Site 40
state: New York
city: Fayetteville
country: United States
facility: Research Site 75
state: North Carolina
city: Mount Airy
country: United States
facility: Research Site 69
state: North Carolina
city: Salisbury
country: United States
facility: Research Site 116
state: North Carolina
city: Columbus
country: United States
facility: Research Site 20
state: Ohio
city: Columbus
country: United States
facility: Research Site 88
state: Ohio
city: Mentor
country: United States
facility: Research Site 109
state: Ohio
city: Springboro
country: United States
facility: Research Site 118
state: Ohio
city: Westlake
country: United States
facility: Research Site 110
state: Ohio
city: North Charleston
country: United States
facility: Research Site 61
state: South Carolina
city: Hermitage
country: United States
facility: Research Site 128
state: Tennessee
city: Kingsport
country: United States
facility: Research Site 114
state: Tennessee
city: Nashville
country: United States
facility: Research Site 60
state: Tennessee
city: Nashville
country: United States
facility: Research Site 103
state: Tennessee
city: Shelbyville
country: United States
facility: Research Site 50
state: Tennessee
city: Beaumont
country: United States
facility: Research Site 115
state: Texas
city: Bellaire
country: United States
facility: Research Site 100
state: Texas
city: Dallas
country: United States
facility: Research Site 98
state: Texas
city: Forney
country: United States
facility: Research Site 99
state: Texas
city: Katy
country: United States
facility: Research Site 68
state: Texas
city: Lewisville
country: United States
facility: Research Site 29
state: Texas
city: Pearland
country: United States
facility: Research Site 32
state: Texas
city: Red Oak
country: United States
facility: Research Site 30
state: Texas
city: San Antonio
country: United States
facility: Research Site 22
state: Texas
city: San Antonio
country: United States
facility: Research Site 26
state: Texas
city: San Antonio
country: United States
facility: Research Site 21
state: Texas
city: Tomball
country: United States
facility: Research Site 80
state: Texas
city: Waco
country: United States
facility: Research Site 134
state: Texas
city: Wichita Falls
country: United States
facility: Research Site 121
state: Texas
city: Ogden
country: United States
facility: Research Site 105
state: Utah
city: Salt Lake City
country: United States
facility: Research Site 57
state: Utah
city: Salt Lake City
country: United States
facility: Research Site 106
state: Utah
city: Sandy
country: United States
facility: Research Site 65
state: Utah
city: South Ogden
country: United States
facility: Research Site 16
state: Utah
city: Chesapeake
country: United States
facility: Research Site 77
state: Virginia
city: Richmond
country: United States
facility: Research Site 136
state: Virginia
city: Morgantown
country: United States
facility: Research Site 97
state: West Virginia
Study officials:
affiliation: Braintree Laboratories / Sebela Pharmaceuticals
name: Leah Hollins
role: STUDY_DIRECTOR
References: