Clinical trial NCT05760313: A Study to Assess Adverse Events and Change in Disease Activity in Pediatric Participants (Age 6 Months to <2 Years) With Functional Constipation Who Are Treated With Linaclotide
Official title: 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 With Functional Constipation (FC).
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Functional Constipation
Keywords: Linaclotide
pediatric functional constipation
Linzess
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
Collaborators: name: Ironwood Pharmaceuticals, Inc.
First posted: 2023-03-08
Enrollment: 19
Sex: ALL
Minimum age (years): 6
Maximum age (years): 23
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: Functional constipation (FC) is a common healthcare problem in children of all ages, potentially due to genetic predisposition, inadequate fiber and fluid intake, and immobility. Currently, there are no pharmacological therapies approved for the treatment of FC. This study will assess adverse events and change in disease activity with linaclotide therapy in participants with FC.

Linaclotide is an approved drug being developed for the treatment of FC in pediatric patients who meet modified Rome IV criteria for childhood FC. In Part 1 of this study, participants are placed in 3 groups, which occur consecutively. Each group receives a different dosage of linaclotide. In Part 2 of the study, participants will be randomly assigned to receive either linaclotide or placebo. There is a 1 in 2 chance that participants will be assigned to placebo. Up to 30 and at least 18 pediatric participants 6 months to less than 2 years of age with FC will be enrolled in the study at approximately 36 sites worldwide.

Participants will receive oral solution of linaclotide prepared from capsule by parent/guardian once daily for 4 weeks.

There may be higher treatment burden for participants in this trial compared to their standard of care (due to study procedures). Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.


Eligibility criteria: Inclusion Criteria:

* Individuals must be 6 months to less than 1 year and 11 months old,, at the time the legally authorized representative (LAR)/parent/guardian signs the informed consent in alignment with local requirements.
* The LAR/parent/guardian who will be completing the electronic diary (eDiary) is able to read and understand the assessments in the eDiary device and must undergo training.
* Participant meets Rome IV criteria for functional constipation (FC): for at least 1 month before Screening (Visit 1), the participant must meet 2 or more of the following:

  * 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)
  * History of excessive stool retention
  * History of painful or hard bowel movements (BMs)
  * History of large-diameter stools
  * Presence of a large fecal mass in the rectum
* LAR/Parent/Guardian is willing to discontinue any laxatives used before the Preintervention Visit in favor of the protocol-permitted rescue medicine.

Exclusion Criteria:

* Participant has conditions that could interfere with drug absorption, including, but not limited to, short bowel syndrome.
* History of clinically significant medical conditions or any other reason that the investigator determines would interfere with the individual's participation in this study or would make the participant an unsuitable candidate to receive study drug.
* Participant has history of:

  * Celiac disease, or positive serological test for celiac disease or the condition is suspected but has not been ruled out by endoscopic biopsy
  * Cystic fibrosis
  * Hypothyroidism that is untreated or treated with thyroid hormone at a dose that has not been stable for at least 3 months prior to Screening (Visit 1)
  * Down's syndrome or any other chromosomal disorder
  * Active anal fissure (investigator has confirmed an active anal fissure and participant reports known anal fissure symptoms \[i.e., streaks of blood on the stool or on diaper or toilet paper and pain/crying with bowel movement within 2 weeks prior to Screening\]). (Note: Anal fissures that have resolved at least 2 weeks prior to screening would not be exclusionary). However, if in the investigator's opinion, an anal fissure(s) may be the primary cause of participant's Rome IV FC criteria, the subject would not be eligible to participate in the study.
  * Anatomic malformations (e.g., imperforate anus, anal stenosis, anterior displaced anus)
  * Intestinal nerve or muscle disorders (e.g., Hirschprung disease, visceral myopathies, visceral neuropathies)
  * Neuropathic conditions (e.g., spinal cord abnormalities, neurofibromatosis, tethered cord, spinal cord trauma)
  * Lead toxicity, hypercalcemia
  * Inflammatory bowel disease
  * Lactose intolerance that is associated with symptoms which could confound the assessments in this study
  * History of cancer. (Note: Participants with a history of cancer are allowed provided that the malignancy has been in a complete remission before enrollment/randomization (Visit 3). A complete remission is defined as the disappearance of all signs of cancer in response to treatment)

Primary outcomes:
measure: Change from baseline in overall Spontaneous Bowel Movement (SBM) frequency rate (SBMs/week) during the Study Intervention Period
timeFrame: Baseline to Week 4
measure: Change from baseline in stool consistency (Bristol Stool Form Scale) during the Study Intervention Period
timeFrame: Baseline to Week 4
measure: Change from baseline in straining during the Study Intervention Period
timeFrame: Baseline to Week 4
measure: Number of Participants with Adverse Events (AEs)
timeFrame: Up to Week 5
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Velocity Clinical Research - Phoenix /ID# 263871
state: Arizona
city: Hot Springs
country: United States
facility: HealthStar Research of Hot Springs PLLC /ID# 251553
state: Arkansas
city: Anaheim
country: United States
facility: Advanced Research Center /ID# 248763
state: California
city: Corona
country: United States
facility: Kindred Medical Institute - Corona /ID# 251535
state: California
city: Washington
country: United States
facility: Velocity Clinical Research Washington DC /ID# 263872
state: District of Columbia
city: Doral
country: United States
facility: Prohealth Research Center /ID# 248696
state: Florida
city: Miami
country: United States
facility: South Miami Medical & Research Group Inc. /ID# 248765
state: Florida
city: Miami
country: United States
facility: Valencia Medical & Research Center /ID# 251533
state: Florida
city: Macon
country: United States
facility: Velocity Clinical Research Macon /ID# 263959
state: Georgia
city: Lafayette
country: United States
facility: Velocity Clinical Research - Lafayette /ID# 263873
state: Louisiana
city: New Market
country: United States
facility: Frederick County Pediatrics /ID# 251555
state: Maryland
city: Farmington Hills
country: United States
facility: Michigan Center of Medical Research /ID# 253536
state: Michigan
city: Hastings
country: United States
facility: Velocity Clinical Research- Hastings Nebraska /ID# 260932
state: Nebraska
city: Charleston
country: United States
facility: Coastal Pediatric Research - West Ashley B /ID# 248693
state: South Carolina
city: Summerville
country: United States
facility: Coastal Pediatric Research - Summerville /ID# 253534
state: South Carolina
city: Houston
country: United States
facility: Houston Clinical Research Associates /ID# 261571
state: Texas
city: Mansfield
country: United States
facility: Prime Clinical Research - Mansfield - East Broad Street /ID# 262947
state: Texas
city: Waxahachie
country: United States
facility: ClinPoint Trials /ID# 251534
state: Texas
city: Plovdiv
country: Bulgaria
facility: UMHAT Sveti Georgi /ID# 250808
city: Ruse
country: Bulgaria
facility: UMHAT Kanev /ID# 248931
city: Sofia
country: Bulgaria
facility: Acibadem City Clinic Tokuda University Hospital EAD /ID# 251232
city: Sofiya
country: Bulgaria
facility: Specialized Hospital For Active Treatment Of Children Diseases Prof. Ivan Mitev /ID# 251229
city: Varna
country: Bulgaria
facility: Nova Clinic /ID# 249023
city: Zagreb
country: Croatia
facility: Klinicki bolnicki centar Sestre milosrdnice /ID# 252798
state: Grad Zagreb
city: Zagreb
country: Croatia
facility: Klinicki bolnicki centar Zagreb /ID# 252796
state: Grad Zagreb
city: Zagreb
country: Croatia
facility: Klinika za dječje bolesti Zagreb /ID# 252792
state: Grad Zagreb
city: Osijek
country: Croatia
facility: Klinicki bolnicki centar Osijek /ID# 252795
state: Osjecko-baranjska Zupanija
city: Muenster
country: Germany
facility: Universitaetsklinikum Muenster /ID# 251965
state: Nordrhein-Westfalen
city: Forchheim
country: Germany
facility: Kinderarztpraxis Dr. Froehlich /ID# 252050
city: Wuppertal
country: Germany
facility: HELIOS Klinikum Wuppertal /ID# 249022
city: Debrecen
country: Hungary
facility: Debreceni Egyetem-Klinikai Kozpont /ID# 250793
state: Hajdu-Bihar
city: Belgrade
country: Serbia
facility: University Children's Hospital 'Tirsova' /ID# 252483
state: Beograd
city: Beograd
country: Serbia
facility: Institut za zdravstvenu zastitu majke i deteta Srbije Dr Vukan Cupic /ID# 252485
city: Novi Sad
country: Serbia
facility: Institute for Child and Youth Health Care of Vojvodina /ID# 252482
city: London
country: United Kingdom
facility: Barts Health NHS Trust /ID# 252298
state: Greater London
city: London
country: United Kingdom
facility: Great Ormond Street Children's Hospital /ID# 253333
state: Greater London
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospitals NHS Foundation Trust /ID# 252299
state: Norfolk
city: Dudley
country: United Kingdom
facility: Russells Hall Hospital /ID# 252660
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: