Clinical Outcomes, Tolerability and Safety of Oral Pantoprazole in Pediatric Participants

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pfizer Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

5 Oct 2021 → 16 Dec 2025

Decision date (initial)

2023-12-21

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Pfizer Inc.

External identifiers

EU CT number

2023-508770-28-00

EudraCT number

2020-005030-15

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To explore the maintenance of healing of erosive esophagitis in participants aged 1 to 11 years and 12 to 17 years.

Secondary objectives 1

1. To explore safety and tolerability of oral pantoprazole.

Conditions and MedDRA coding

EROSIVE ESOPHAGITIS

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Participants must have a documented erosive lesion with an LA Grade of A to D prior to starting PPI treatment: a. A participant who enters the study before the diagnostic EGD has been performed must have recorded a CSS ≥16 on the GASP-Q or a CSS ≥8 on the GSQ-YC as appropriate, at Screening, in order to enter the study. Once enrolled, this participant will undergo an initial EGD to confirm the presence of EE. Note: If an EE lesion is confirmed by the initial diagnostic EGD, the participant can be enrolled in the study. If no EE lesion is confirmed by the initial endoscopy, the participant will be terminated from the study. b. The following criteria apply to a participant who undergoes screening for the study after a diagnostic EGD has already confirmed the presence of an EE lesion: - The initial diagnostic EGD must have been performed no more than 12 weeks prior to study entry; - The EGD report must be available and must indicate the presence of anEE lesion; - If the participant has already started PPI treatment to heal the lesion before entering the study, but has not completed at least 8 weeks of healing therapy, the participant must continue treatment with the same PPI for a total of up to 8 weeks, after which follow-up EGD will be performed at the end of Week 8 to confirm healing of the lesion; - If the participant began healing treatment with a PPI other than pantoprazole prior to study enrollment, that PPI must be approved for the treatment of erosive esophagitis in pediatric participants and the dose being taken must be according to the local prescribing information; - If the participant began healing treatment with pantoprazole prior to study enrollment, the dose of pantoprazole being taken must be consistent with the dosing scheme for the Healing Phase of the protocol. c. The following criteria apply to a participant who undergoes screening for the study after a diagnostic EGD has already confirmed the presence of an EE lesion and after they have completed at least 8 weeks of healing therapy with a PPI: - The initial diagnostic EGD must have been performed no more than 12 weeks prior to study entry; - The EGD report must be available and must indicate the presence of an EE lesion, including photographic evidence of the lesion; - The participant will enter the study at the end of Week 8 and will undergo follow-up EGD to confirm lesion healing, if that has not already been done, prior to being randomized into the Maintenance Phase of the study.
2. Capable of giving signed informed consent/assent, which includes compliance with the requirements and restrictions listed in the ICD and in the protocol.
3. Willingness and ability of the participant or parent/legal guardian to complete the eDiary including the GASPQ or GSQ-YC, PGIS or P-RGIS, study intervention log, and rescue medicine log, throughout the study.
4. Willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures, including the use of the eDiary.
5. Male and female participants aged 1 to 17 years.
6. Minimum body weight 7 kg
7. Females of childbearing or non-childbearing potential may be enrolled in the study: To be considered a female of non-childbearing potential, the participant must meet at least 1 of the following criteria: - Premenarchal: The investigator (or other appropriate staff) must discuss the participant's premenarchal status with the participant and parent/legal guardian at office visits and during telephone contacts, as participants who achieve menarche during the study would no longer be considered "female participants of non-childbearing potential" and must comply with the protocol requirements applicable to women of childbearing potential.

Exclusion criteria 17

1. Previous administration of an investigational drug or vaccine within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer). Note: local regulations or other factors may require more than 30 days.
2. Children that may be at high risk from procedural sedation should be carefully evaluated. Participants with a history of complications during prior procedural sedation (eg, for upper endoscopy) should be excluded. Participants graded as ASA Classification System I or II only should be included (See Section 8.1.3.8 of the protocol).
3. History or presence of upper gastrointestinal anatomic or motor disorders, including the following: • Esophageal strictures, webs, diverticula, or other gastroduodenal pathology seen on EGD. • Gastrointestinal strictures of any kind. • Esophageal or gastric motor disorders (eg, scleroderma). • Barrett's esophagus. • Peptic ulcer disease, erosive gastritis and/or erosive duodenitis. • Eosinophilic esophagitis by histology (eosinophils per high powered field). • Gastrointestinal malabsorption. • H. pylori infection within the past 6 months. • Cystic Fibrosis
4. Family history of malignant hyperthermia
5. Known hypersensitivity to any PPI, including pantoprazole or to any substituted benzimidazole or to any of the excipients.
6. Any disorder requiring chronic (daily) use of warfarin, heparin, other anticoagulants, methotrexate, atazanavir or nelfinavir, clopidogrel, or potent inhibitors or inducers of CYP2C19 (eg, phenytoin, sulfamethoxazole, valproic acid, carbamazepine, and griseofulvin).
7. Serum creatine kinase levels >3 x upper limit of normal.
8. Known history of human immunodeficiency virus or clinical manifestations of acquired immune deficiency syndrome.
9. Active malignancy of any type, or history of a malignancy. Participants with a history of malignancies that have been surgically removed or eradicated by irradiation or chemotherapy and who have no evidence of recurrence for at least 5 years before Screening are acceptable.
10. Diagnosed as having or has received treatment for esophageal, gastric, pyloric channel, or duodenal ulceration within 30 days before the Screening visit.
11. ALT or BUN >2.0 ULN or estimated creatinine >1.5 X ULN for age or any other laboratory abnormality considered by the Investigator to be clinically significant within 14 days before the Baseline Visit (Day 1).
12. Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or study intervention administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.
13. Has, in the Investigator's opinion, a serious chronic condition (eg, diabetes, epilepsy), which is either not stable or not well controlled and may interfere with the conduct of the study.
14. Has any condition possibly affecting drug absorption (eg, gastrectomy).
15. Frequent, repeated use of oral or parenteral glucocorticoids (eg, prednisone, prednisolone, dexamethasone). Steroid inhalers and topical steroids may be used.
16. Pregnant female participants; breastfeeding female participants.
17. Is unwilling or unable to comply with the Lifestyle Considerations section (Section 5.3) described in the protocol.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Endoscopically confirmed maintenance of healing of erosive esophagitis at Week 24

Secondary endpoints 1

1. Safety and tolerability will be assessed by physical examinations, AE monitoring, clinical laboratory measurements, blood pressure, and pulse rate.

Investigational products

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

Test 4

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pfizer Inc.

Sponsor organisation

Pfizer Inc.

Address

66 Hudson Boulevard East

City

New York

Postcode

10001-2189

Country

United States

Scientific contact point

Organisation

Pfizer Inc.

Contact name

Nancy Sherman

Public contact point

Organisation

Pfizer Inc.

Contact name

Nancy Sherman

Third parties 3

Locations

2 EU/EEA countries · 4 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 18 files

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

Application history

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