Functional Constipation: A Phase 2 Dose Finding Study Evaluating the Safety and Efficacy of Linaclotide in Pediatric Subjects 6 Months to Less Than 2 Years of Age

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Abbvie Deutschland GmbH & Co. KG

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

5 Dec 2023 → 9 Jun 2025

Decision date (initial)

2023-10-11

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AbbVie Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

Objective for Part 1: To identify a tolerable, safe, and efficacious dose of linaclotide administered for 4 weeks in pediatric subjects, 6 months to less than 2 years of age, with FC for Part 2.

Objective for Part 2: To evaluate the safety and efficacy of 4 weeks of study intervention with linaclotide in pediatric participants, 6 months to less than 2 years of age, with FC.

Conditions and MedDRA coding

Functional Constipation (FC)

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-000927-PIP01-10

Plan to share IPD

Yes

IPD plan description

AbbVie is committed to responsible clinical trial data sharing. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information. To learn more about the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/ For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. The Subjects' LAR/parent/guardian must voluntarily sign and date an informed consent, approved by an independent ethics committee (IEC)/institutional review board (IRB), prior to the initiation of any screening or study-specific procedures.
2. Individuals must be 6 months to less than 1 year and 11 months old, at the time the LAR/parent/guardian signs the informed consent in alignment with local requirements.
3. Subject has weight-for-height/length ratio of ≥ 3rd percentile for age 6 months to less than 24 months at the time the LAR/parent/guardian has provided signed consent. (Investigators can choose to use CDC or WHO growth charts based on their current clinical practice).
4. Subject meets Rome IV criteria for FC as outlined below: For at least 1 month before Screening (Visit 1), the subject must meet 2 or more of the following (a-e): a) 2 or fewer defecations per week (with each defecation occurring in the absence of any laxative, suppository, or enema use during the preceding 24 hours) b) History of excessive stool retention c) History of painful or hard bowel movements (BMs) d) History of large-diameter stools e) Presence of a large fecal mass in the rectum Accompanying symptoms may include irritability, decreased appetite, and/or early satiety.
5. Based on the eDiary, the Subject has an average of ≤ 2 spontaneous bowel movements (SBMs) per week during the 14 days before the enrollment/randomization day and up to the enrollment/randomization (including the morning eDiary assessments reported before administration of first dose of study intervention on the enrollment/randomization day). An SBM is defined as a bowel movement (BM) that occurs in the absence of laxative, enema, or suppository use on the calendar day of the BM or the calendar day before the BM.

Exclusion criteria 6

1. Subjects with conditions that could interfere with drug absorption including but not limited to short bowel syndrome.
2. Subjects with history of clinically significant medical conditions or any other reason that the investigator determines would interfere with the subject's participation in this study or would make the subject an unsuitable candidate to receive study drug.
3. Subjects with conditions of unexplained AND clinically significant alarm symptoms (lower gastrointestinal [GI] bleeding [rectal bleeding or heme-positive stool], iron-deficiency anemia, or any unexplained anemia, or weight loss) and systemic signs of infection or colitis, or any neoplastic process
4. Subjects with suspected mechanical bowel obstruction or pseudo-obstruction
5. Subject did not use a protocol-specified prohibited medicine before the start of the Preintervention Period (Visit 2) or failed to meet the stable-dose requirements of certain medications
6. Subject must not have been treated with any investigational drug within 30 days or 5 half-lives of the drug (whichever is longer) prior to Screening (Visit 1) or is currently or planning to enroll in another clinical study or was previously enrolled in this study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Change from baseline in 4-week overall SBM frequency rate (SBMs/week) during the Study Intervention Period
2. Change from baseline in 4-week stool consistency (Bristol Stool Form Scale) reported by legally authorized representative (LAR)/parent/guardian/caregiver during the Study Intervention Period
3. Change from baseline in 4-week straining reported by LAR/parent/guardian/caregiver during the Study Intervention Period

Investigational products

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

Test 3

Placebo 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Abbvie Deutschland GmbH & Co. KG

Sponsor organisation

Abbvie Deutschland GmbH & Co. KG

Address

Knollstrasse

City

Ludwigshafen Am Rhein

Postcode

67061

Country

Germany

Scientific contact point

Organisation

Abbvie Deutschland GmbH & Co. KG

Contact name

Global Clinical Trials Helpdesk

Public contact point

Organisation

Abbvie Deutschland GmbH & Co. KG

Contact name

Global Clinical Trials Helpdesk

Third parties 7

Locations

4 EU/EEA countries · 13 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 20 files

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

Application history

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