Performance and Safety of Afluxin® in Patients With Gastroesophageal Reflux Disease

Devintec Sagl208 enrolled

Overview

Gastroesophageal Reflux Disease (GERD) is a chronic condition in which stomach acid flows back into the esophagus, causing irritation and inflammation. GERD is categorized into Nonerosive Reflux Disease (NERD), Erosive Esophagitis (EE), and Barrett's esophagus (BE). Common symptoms include heartburn and acid regurgitation. Lifestyle factors such as smoking, obesity, and Helicobacter pylori infection can increase the risk of developing GERD. The clinical management of GERD typically involves Proton Pump Inhibitors (PPIs) therapy, which, although effective, may not benefit all patients and can be associated with long-term risks. The American College of Gastroenterology (ACG) suggests PPIs discontinuation or on-demand therapy for uncomplicated GERD after an 8-week trial. However, evidence indicates that PPIs are used more frequently, often long-term and in high doses, and not necessarily according to recommendations. Moreover, the availability of Over-The-Counter (OTC) PPIs has led to prolonged use by patients without medical guidance. Concerns have been raised due to potential side effects of long-term PPIs use, including enteric, respiratory, and urinary tract infections, as well as an increased risk of vitamin and mineral deficiencies and osteoporosis. Alternatives to PPIs include Histamine-2 Receptor Antagonists (H2RAs), antacids and alginate-based formulations. Among OTC treatments, medical devices formulated with natural components are also gaining attention for their potential performance and tolerability in managing mild to moderate GERD symptoms. These alternatives could address the unmet needs of NERD patients, especially those with a low response to PPIs treatment and provide an option without the potential side effects of prolonged PPIs use. Afluxin® is a class III medical device, containing functional substances (tamarind seed polysaccharide, pea protein and polyacrylic acid), formulated for the treatment of mild to moderate GERD. Preclinical data have shown that Afluxin® is able to create a protective barrier over the gastroesophageal epithelium, preventing reflux damage. In vitro studies suggest that Afluxin® effectively binds to the esophageal and gastric mucosa, reducing abnormal permeability caused by acid reflux. Moreover, in vivo evidence shows that Afluxin® can increase gastric pH, reduce epigastric pain, esophageal damage, and inflammatory markers associated with GERD. Given the encouraging results obtained in preclinical investigations, this study is designed to provide clinical evidence to support the performance and safety of Afluxin® in reducing gastrointestinal symptoms of patients with mild to moderate GERD in a multicenter, randomized, double-blind, parallel-group, Afluxin® stick pack vs. inactive control clinical investigation.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Male and female patients, aged ≥ 18 years and ≤ 75 years. 2. Evidence of symptomatic GERD: patients with ongoing heartburn and/or regurgitation (with or without dyspepsia symptoms of epigastric pain and/or burning) of at least mild to moderate severity or experienced during the least 7 days before starting the treatment, as assessed on a clinical basis by the Investigator. 3. Patients not pre-treated with PPIs, even for problems different from GERD (e.g., gastroprotection, PPI-based triple or quadruple therapy for eradication of H. pylori), H2RAs, and/or with antiacids, alginates or medical devices made of substances (i.e., substance-based medical devices to treat GERD, gastroesophageal reflux and similar conditions) in the last week prior to screening. 4. Patient has provided written informed consent after being informed of the study procedures and risks prior to any study-related events. 5. Patients are able to understand and adhere to the study procedures. 6. Females of childbearing potential must have a negative urine pregnancy test (dipstick) at Visit 1 and currently use or agree to use consistently and correctly (i.e., perfect use) a highly effective or acceptable effective contraceptive method for the individual subject and her partner(s) throughout the study treatment period. Exclusion Criteria: 1. Patient with hypersensitivity to any Afluxin® or inactive control components. 2. Rhinosinusitis or bronchitis. 3. Patients with a: 1. history and/or 2. symptom profile and/or 3. discovered on endoscopy suggestive of the following: any other Gastrointestinal (GI) disease, erosive GERD, BE, acute peptic ulcer and/or ulcer complications, hiatus hernia with a diameter which exceeds 3 cm, Zollinger-Ellison syndrome, esophageal or gastric cancer, pyloric stenosis, esophageal or gastric surgery, intestinal obstruction, current pernicious anemia, indication for H. pylori eradication therapy, known gastro-intestinal bleeding (hematochezia or hematemesis) within the last 12 months. 4. Patients diagnosed with functional dyspepsia characterized by postprandial distress syndrome (i.e., bothersome postprandial fullness and/or early satiation). 5. Patients with a history of gastro-esophageal surgery, anti-reflux, or bariatric procedure. 6. Presence of any active malignancy (except for non-invasive basal or squamous cell carcinoma of the skin). 7. Patients using any drug that could affect symptoms or affecting the gastrointestinal tract during the last week prior to screening: 1. prokinetics 2. systemic glucocorticosteroids 3. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) 8. Patients who are pregnant or lactating. 9. Patients who are enrolled in or have participated in other clinical trials or investigations within 30 days prior to screening. 10. Clinically significant or unstable concurrent diseases whose sequelae or treatment might contraindicate study participation or interfere with the study evaluation parameters, as judged by the Investigator.

Locations (7)

IRCCS Policlinico San Martino

Genova, Italy

RECRUITING

IRCCS Ca' Granda Ospedale Maggiore Policlinico Foundation

Milan, Italy

RECRUITING

AOU Federico II di Napoli

Naples, Italy

RECRUITING

Azienda Ospedale Università Padova

Padova, Italy

RECRUITING

S. Andrea Ospedale Universitario

Roma, Italy

RECRUITING

Humanitas Research Hospital

Rozzano (MI), Italy

RECRUITING

A.O.U. Città della Salute e della Scienza di Torino

Torino, Italy

RECRUITING

Outcomes

Primary Outcomes

Assess the superiority of a 7-day treatment course with Afluxin® over inactive control in terms of difference between treatment groups in terms of proportion of responders

The primary endpoint is the difference between treatment groups (Afluxin® and placebo) in terms of proportion of responders, defined as patients who report a reduction in the GERD dimension of the RDQ (Reflux Disease Questionnaire) equal to 1.5 points (clinically significant difference, according to Wilkinson et al., 2019), between baseline and the end of the 7-day treatment. In the RDQ questionnaire validated in Italian language, patients are asked to rate GERD-related symptoms they have been experiencing over the past 7 days. The questionnaire consists of 12 items to report the frequency and severity of heartburn, regurgitation and dyspepsia. In this study the two subscales for heartburn and regurgitation will be combined into the GERD dimension. Symptom frequency and severity will be measured on 6-point scales (ranging from 0=none to 5 =daily/severe).

Time frame: From enrollment to the end of the 7-day treatment

Secondary Outcomes

RDQ GERD dimension, including single item scores

GERD dimension evaluated through the RDQ (Reflux Disease Questionnaire) and evaluation of the single item scores, at the baseline and at the end of the 7-day treatment. In the RDQ questionnaire validated in Italian language, patients are asked to rate GERD-related symptoms they have been experiencing over the past 7 days. The self-assessed questionnaire will consist of 12 items to report the frequency and severity of heartburn, regurgitation and dyspepsia. The two subscales for heartburn and regurgitation will be combined into the GERD dimension. Symptom frequency and severity will be measured on 6-point scales (ranging from 0=none to 5 =daily/severe).

Time frame: Baseline and at the end of the 7-day treatment

RDQ dyspepsia dimension total and single item scores

Dyspepsia dimension evaluated through the RDQ (Reflux Disease Questionnaire) total and single item scores, at the baseline and at the end of the 7-day treatment. In the RDQ questionnaire validated in Italian language, patients are asked to rate GERD-related symptoms they have been experiencing over the past 7 days. The self-assessed questionnaire will consist of 12 items to report the frequency and severity of heartburn, regurgitation and dyspepsia (burning/pain in the upper stomach). Symptom frequency and severity will be measured on 6-point scales (ranging from 0=none to 5 =daily/severe).

Time frame: Baseline and at the end of the 7-day treatment

Total and single item scores of the Reflux Symptom Index (RSI)

Total and single item scores of the Reflux Symptom Index (RSI) at baseline and at the end of the 7-day treatment, assessing the severity of Laryngopharyngeal Reflux (LPR) symptoms. The RSI validated in Italian language, will be used for the evaluation of LPR symptoms that patients have been experiencing within the last month. The RSI examines 9 items, to be scored from 0 (no problem) to 5 (severe problem), with a higher score indicating a higher severity of the symptom (range of total score: 0-45) .

Time frame: Baseline and at the end of the 7-day treatment

Severity of GERD cardinal symptoms (i.e., heartburn and regurgitation)

Severity of GERD cardinal symptoms (i.e., heartburn and regurgitation) throughout the 7-day treatment, as self-assessed daily by patients using a 7-point Likert scale ranging from 1 = no discomfort to 7 = very severe discomfort.

Time frame: Throughout the 7-day treatment

Severity of LPR symptoms (i.e., hoarseness/clearing the throat and troublesome cough)

Severity of (Laryngopharyngeal Reflux) LPR symptoms (i.e., hoarseness/clearing the throat and troublesome cough) throughout the 7-day treatment, as self-assessed daily by patients using a 7-point Likert scale ranging from 1 = no discomfort to 7 = very severe discomfort.

Time frame: Throughout the 7-day treatment

Number and percentage of patients with occurrence of symptoms during the night

Number and percentage of patients with occurrence of symptoms during the night throughout the 7-day treatment

Time frame: Throughout the 7-day treatment

Mean time to alleviation of symptoms following treatment administration

Mean time to alleviation of symptoms following treatment administration throughout the 7-day treatment, as self-assessed daily by patients

Time frame: Throughout the 7-day treatment

Number and percentage of patients with complete remission of symptoms

Number and percentage of patients with complete remission of symptoms at the end of the 7-day treatment, defined as an RDQ (Reflux Disease Questionnaire) GERD dimension total score = 0 points. In the RDQ questionnaire validated in Italian language, patients are asked to rate GERD-related symptoms they have been experiencing over the past 7 days. The self-assessed questionnaire will consist of 12 items to report the frequency and severity of heartburn, regurgitation and dyspepsia. Symptom frequency and severity will be measured on 6-point scales (ranging from 0=none to 5 =daily/severe).

Time frame: At the end of the 7-day treatment

Mean score on the self-report measure Patient's Global Impression of Change (PGI-C)

Mean score on the self-report measure Patient's Global Impression of Change (PGI-C) at the end of the 7-day treatment, assessing the patient's overall perceived change in their condition. The self-report measure PGI-C will be used to assess the overall perceived improvement at the end of the 7-day treatment. Patients will reply to the general statement "Since the start of the study, my overall status is'", using the following 7-point scale: 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, and 7=very much worse.

Time frame: At the end of the 7-day treatment

Number and percentage of patients who take prohibited medications

Number and percentage of patients who take prohibited medications (Proton Pump Inhibitors, Histamine-2 Receptor Antagonists, antiacid, alginates or medical devices made of substances).

Time frame: Throughout the 7-day treatment

Patient's compliance with treatment

Patient's compliance with treatment protocol, in terms of adherence to the instructions and recommendations of the study treatment protocol. The information are recorded on the patient's diary and reviewed by the investigators. Patient differences in % compliance between the two treatments will be calculated.

Time frame: Throughout the 7-day treatment

Patient's satisfaction with treatment

Patient's satisfaction with treatment, as self-assessed by the patient using a 5-point response scale, at the end of the 7-day treatment. At the end of the 7-day treatment the patient will record his/her opinion of satisfaction with treatment in the e-diary, answering the question: "How satisfied are you with the study treatment you received?" with a 5-point response scale (1=unsatisfied, 2=somewhat unsatisfied, 3=neutral, 4=somewhat satisfied, 5=satisfied).

Time frame: At the end of the 7-day treatment

Safety: adverse events and device deficiencies

Incidence and type of AEs and DDs continuously monitored during the study

Time frame: Throughout the 7-day treatment

Performance and Safety of Afluxin® in Patients With Gastroesophageal Reflux Disease

Overview

Conditions

Interventions

Eligibility

Locations (7)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts