Efficacy and Safety Evaluation of Esomeprazole Magnesium in Maintaining Healing of Erosive Esophagitis in Pediatric Patients Aged 1 to 11 Years
- Trial ID
- 2023-505454-18-00
- Protocol
- D9612C09998
- Sponsor
- AstraZeneca AB
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this Phase III study is to evaluate the **efficacy** and **safety** of NEXIUM for the maintenance of healing of **Erosive Esophagitis** (EE) in pediatric patients aged 1 to 11 years. This is clinically relevant as maintaining healing in EE is crucial to prevent complications such as strictures and to improve the quality of life in affected children.
Secondary objectives include:
- Healing phase: To assess the efficacy and safety of NEXIUM for the healing of EE in pediatric patients aged 1 to 11 years.
- Maintenance phase: To assess symptoms during the 16-week maintenance phase.
Participants
The clinical trial involves a total of **46 participants** diagnosed with **Erosive Esophagitis**. The study population consists of pediatric patients aged 1 to 11 years, inclusive, with both male and female subjects being eligible. Participants are required to have a history of gastroesophageal reflux disease (GERD) for at least three months prior to the study and must have confirmed healing of Erosive Esophagitis at the end of the healing phase. The trial includes a vulnerable population, as it involves children. Participants must weigh at least 10 kg, and postmenarcheal female patients are required to have a negative pregnancy test before starting treatment. The selection process ensures that all participants have completed the healing phase and have endoscopy-verified healed Erosive Esophagitis. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The sponsor has not provided additional information regarding the selection criteria beyond the inclusion of both genders and the specified age range.
Plans and Procedures
The clinical trial is designed to evaluate the **efficacy** and safety of NEXIUM for the maintenance of healing of **erosive esophagitis** in pediatric patients aged 1 to 11 years. This is a Phase III, randomized, double-blind, controlled study. The trial is structured into two main phases: an 8-week healing phase followed by a 16-week maintenance phase, resulting in a total trial duration of 24 weeks. Participants will be randomly assigned to receive either NEXIUM or a control treatment, with neither the participants nor the investigators aware of the treatment assignments, ensuring a double-blind methodology.
The study will commence with an inclusion (screening) visit, where eligibility criteria will be assessed, including a history of gastroesophageal reflux disease (GERD) for at least three months and confirmation of erosive esophagitis via endoscopy. Participants must weigh at least 10 kg and meet other specific criteria, such as a negative pregnancy test for postmenarcheal females. Following the screening, eligible participants will enter the healing phase, during which the presence or absence of erosive esophagitis will be evaluated at the end of the 8-week period through endoscopic assessment.
Upon successful completion of the healing phase, participants with endoscopy-verified healed erosive esophagitis will transition into the maintenance phase. The primary endpoint for this phase is the presence or absence of erosive esophagitis at the end of the 16-week period, assessed through endoscopy. Safety and tolerability will be monitored throughout the trial, with assessments including adverse events, vital signs, and clinical laboratory variables. Follow-up visits will occur at regular intervals to monitor these parameters and ensure participant safety.
The expected length of participant involvement is approximately 24 weeks, encompassing both the healing and maintenance phases. Conditions that may lead to early termination from the study include the occurrence of serious adverse events, non-compliance with study procedures, or withdrawal of consent by the participant's guardian. The trial is anticipated to conclude by August 2026, with recruitment having started in July 2022. The study aims to provide valuable insights into the long-term management of erosive esophagitis in the pediatric population.
Treatment
The clinical trial involves the administration of **NEXIUM 10 mg gastro-resistant granules for oral suspension, sachet**. This experimental medication contains the active substance **esomeprazole magnesium**, a chemical compound. The pharmaceutical form is gastro-resistant granules intended for oral suspension, provided in sachets. The maximum daily dose is 10 mg, with a total maximum dose of 1680 mg over a treatment period of 24 weeks. The route of administration is oral, and the medication is manufactured by AstraZeneca UK Limited. The product has undergone secondary packaging and labeling specifically for the clinical trial.
Another experimental treatment in the study is **Esomeprazole Magnesium** in the form of an oral suspension. This formulation also contains **esomeprazole magnesium** as the active ingredient, produced by AstraZeneca AB. The maximum daily dose for this formulation is 20 mg, with a total maximum dose of 3360 mg over the same 24-week treatment period. The administration route is oral, and the formulation is chemically derived.
The study also includes a lower dosage form of **Esomeprazole Magnesium** oral suspension, containing the same active substance, **esomeprazole magnesium**. This formulation is also produced by AstraZeneca AB. The maximum daily dose for this variant is 5 mg, with a total maximum dose of 840 mg over 24 weeks. The administration is oral, and the formulation is chemically based.
Throughout the trial, participant compliance with the dosing schedule will be monitored to ensure adherence to the prescribed treatment regimen. No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified in the trial data provided.
Efficacy
Efficacy in this clinical trial will be assessed through the evaluation of the presence or absence of **Erosive Esophagitis (EE)** in pediatric patients aged 1 to 11 years. The primary endpoint for the maintenance phase is the assessment of EE via esophagogastroduodenoscopy (EGD) at the end of the 16-week maintenance phase. Secondary endpoints include the presence or absence of EE at the end of the 8-week healing phase and the percentage of days without rescue medication during both the 8-week healing phase and the 16-week maintenance phase.
Safety and tolerability will also be evaluated as part of the efficacy assessment. This includes monitoring adverse events (AEs), vital signs, and clinical laboratory variables. The parameters for AEs include occurrence, frequency, relationship to the investigational medicinal product (IMP), intensity, seriousness, and any AEs leading to discontinuation of the IMP. Vital signs will be measured by assessing systolic and diastolic blood pressure, pulse, and body weight.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Patient must be 1 to 11 years of age, inclusive, at the time of their guardian signing the informed consent and the patient signing the informed assent (if applicable).
- Patients must have a history of GERD for at least 3 months before the start of study treatment in the healing phase, as judged by the Investigator.
- For the healing phase: Patients must have confirmed presence of EE at endoscopy performed within one week of the start of the healing phase.
- For the maintenance phase: Patients must have completed the healing phase and have endoscopy-verified healed EE (Grade 0 ie, no LA Grade A, B, C, or D) at the 8-week endoscopy visit.
- Patients must weigh ≥ 10 kg.
- Patients may be male or female.
- All postmenarcheal female patients must have a negative pregnancy test (urine) before starting treatment. Sexually active patients must be abstinent or maintain effective contraception from informed consent day up to the last day of IMP treatment. Sexually active postmenarcheal female patients must agree to the simultaneous use of 2 medically accepted methods of contraception from Day 1 until 3 days after the last dose of study medication. At least one method of contraception must be highly reliable (ie, can achieve a failure rate of < 1% per year), such as stable oral, implanted, transdermal, or injected contraceptive hormones associated with inhibition of ovulation, or an intrauterine device in place for at least 3 months. The other method of contraception must be a barrier method, such as a diaphragm with spermicide or male partner's use of male condom with spermicide. NOTE: Prior to menarche, pregnancy testing is not required. However, the patient and their parent/guardian must be advised that, immediately upon menarche, the patient will be required to begin pregnancy testing and, if deemed necessary by the Investigator, initiate contraceptive use.
- Patient’s guardian must be capable of giving signed informed consent as described in Appendix A, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. Assent forms will be signed by patients who are old enough to express their general understanding of the study as per local regulations.
Exclusion Criteria
- Presence of other diseases, such as severe heart, lung, liver, renal, blood, or neurological disease or similar, that the Investigator judges could be a risk for the patient or impact the ability to participate in the study (patients with neurological disabilities or hiatal hernia may be included if the Investigator considers it appropriate).
- Significant clinical illness within 4 weeks prior to the start of treatment, eg, unintentional weight loss, gastrointestinal bleeding requiring abstinence from food, jaundice, or any other signs indicating serious or malignant diseases
- Any conditions that are predicted to require a surgery during the study period (from the day of informed consent to the day of the last scheduled visit).
- Previous total gastrectomy.
- Anticipated need for concomitant therapy with any of the following after enrollment in this study: − PPIs (except for the IMPs) − H2-receptor antagonists − Anticholinergic agents for gastrointestinal-related diseases or symptoms − Prostaglandin analog indicated for peptic ulcers (eg, misoprostol) − Gastrointestinal promotility drugs − Bismuth-containing drugs − Mucosal protectants (antacids are accepted as rescue medication) − Any drug known to have the potential for a drug-drug interaction with NEXIUM (eg, atazanavir sulfate, nelfinavir mesylate, saquinavir mesylate, ritonavir, rilpivirine hydrochloride, diazepam, phenytoin, cilostazol, high-dose methotrexate, warfarin, tacrolimus hydrate [except external use], digoxin, methyldigoxin, itraconazole, ketoconazole, voriconazole, erlotinib, gefitinib, nilotinib, clopidogrel, rifampicin, clarithromycin, cisapride, citalopram, imipramine, clomipramine, and St John’s wort, etc). If relevant, please consult the current IB for details.
- Participation in another clinical study with an IMP administered in the last 4 weeks before enrollment.
- Patients with a known hypersensitivity to NEXIUM, or any other PPI, or any of the excipients of the product
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
- Judgment by the Investigator that the patient should not participate in the study if the patient or guardian is unlikely to comply with study procedures, restrictions, and requirements.
- Previous screening, or enrollment and randomization in the present study.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Recruiting | 01 Jul 2022 | 4 |
 Greece | Not Recruiting | 01 Jul 2022 | 10 |
 Italy | Not Recruiting | 01 Jul 2022 | 18 |
 Lithuania | Not Recruiting | 01 Jul 2022 | 4 |
 Portugal | Not Recruiting | 01 Jul 2022 | 12 |
 Spain | Not Recruiting | 01 Jul 2022 | 6 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Esomeprazole Magnesium | Test | ORAL SUSPENSION | ORAL USE | 20 | 24 | PRD10361845 |
Esomeprazole Magnesium | Test | ORAL SUSPENSION | ORAL USE | 5 | 24 | PRD10361843 |
NEXIUM 10 mg gastro-resistant granules for oral suspension, sachet | Test | GASTRO-RESISTANT GRANULES FOR ORAL SUSPENSION, SACHET | ORAL USE | 10 | 24 | PRD400466 |