Endoscopic evidence of maintenance of healing with oral NEXIUM in patients 1 to 11 years old with erosive esophagitis.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Astrazeneca AB

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

24 Nov 2021 → ongoing

Decision date (initial)

2024-04-12

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Astrazeneca AB

External identifiers

EU CT number

2023-505454-18-00

EudraCT number

2020-002515-21

ClinicalTrials.gov

NCT05267613

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Dose response, Therapy, Efficacy

Maintenance phase:
• To assess the efficacy and safety of NEXIUM for the maintenance of healing of EE in pediatric patients 1 to 11 years of age

Secondary objectives 2

1. Healing phase: • To assess the efficacy and safety of NEXIUM for the healing of EE in pediatric patients 1 to 11 years of age
2. Maintenance phase: • To assess symptoms during the 16-week maintenance phase

Conditions and MedDRA coding

Erosive Esophagitis

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 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).
2. 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.
3. For the healing phase: Patients must have confirmed presence of EE at endoscopy performed within one week of the start of the healing phase.
4. 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.
5. Patients must weigh ≥ 10 kg.
6. Patients may be male or female.
7. 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.
8. 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 10

1. 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).
2. 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
3. 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).
4. Previous total gastrectomy.
5. 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.
6. Participation in another clinical study with an IMP administered in the last 4 weeks before enrollment.
7. Patients with a known hypersensitivity to NEXIUM, or any other PPI, or any of the excipients of the product
8. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
9. 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.
10. Previous screening, or enrollment and randomization in the present study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Maintenance phase: • Presence/absence of EE for all patients by assessment of EGD at the end of the 16-week maintenance phase
2. • Safety and tolerability will be evaluated in terms of AEs, vital signs, and clinical laboratory variables. Assessments related to AEs cover:  Occurrence/frequency  Relationship to IMP as assessed by the investigator  Intensity  Seriousness  Death  AEs leading to discontinuation of IMP Vital signs parameters include systolic and diastolic blood pressure, and pulse as well as body weight.

Secondary endpoints 4

1. Healing phase: • Presence/absence of EE for all patients by assessment of EGD at the end of the 8-week healing phase
2. • The percentage of days without rescue medication during the 8-week healing phase
3. • Safety and tolerability will be evaluated in terms of AEs, vital signs, and clinical laboratory variables Assessments related to AEs cover:  Occurrence/frequency  Relationship to IMP as assessed by the investigator  Intensity  Seriousness  Death  AEs leading to discontinuation of IMP Vital signs parameters include systolic and diastolic blood pressure, and pulse as well as body weight.
4. Maintenance phase: • The percentage of days without rescue medication during the 16-week maintenance phase

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Astrazeneca AB

Sponsor organisation

Astrazeneca AB

Address

Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

Astrazeneca AB

Contact name

Sarath Mundra

Public contact point

Organisation

Astrazeneca AB

Contact name

Sarath Mundra

Third parties 10

Locations

6 EU/EEA countries · 22 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 104 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

13 submissions — initial application plus substantial / non-substantial modifications