Clinical trial NCT05652205: A Study to Assess Adverse Events and Change in Symptoms With Linaclotide Versus Placebo in Pediatric Subjects, Ages 2 to 5 Years, With Functional Constipation
Official title: A Phase 3, Multicenter, Randomized, Double-blind, Parallel-group, Safety and Efficacy Study of Linaclotide Versus Placebo in Pediatric Subjects, Ages 2 to 5 Years, With Functional Constipation (FC) With a 24-week Open-label Treatment Extension
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Functional Constipation (FC)
Chronic Idiopathic Constipation (CIC)
Keywords: Functional Constipation (FC)
Linaclotide
AGN-182139
Linzess
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
Collaborators: name: Ironwood Pharmaceuticals, Inc.
First posted: 2022-12-15
Enrollment: 123
Sex: ALL
Minimum age (years): 2
Maximum age (years): 5
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, ages 2 to 5, who meet modified Rome IV criteria for childhood FC. In Part 1 of this study, participants are placed in 1 of 2 groups, called treatment arms. Each group receives a different treatment. There is a 1 in 2 chance that participants will be assigned to placebo. All participants in Part 2 will receive linaclotide. Approximately 116 participants aged 2 to 5 years with FC will be enrolled in this study at around 45 sites worldwide.

Participants will receive daily doses of oral Linaclotide capsules or matching placebo for 12 weeks in Part 1 of the study. In Part 2, the open label long-term safety extension, participants with FC who completed study intervention in Part 1 of Study M21-572 or the Phase 2 Study LIN-MD-67 will receive linaclotide for 24 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 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:

* Caregiver/parent/guardian/legally authorized representative (LAR) is willing and able to comply with procedures required in this protocol, prior to the initiation of any screening or study-specific procedures. In addition, the caregiver/parent/guardian/LAR who will be completing the electronic diary (eDiary) must be able to read and understand the assessments in the eDiary device and undergo training.
* Participant meets modified Rome IV criteria for FC: For at least 1 month before Screening (Visit 1), the participant has had 2 or fewer defecations (with each defecation occurring in the absence of any laxative, suppository, or enema use during the preceding 24 hours) per week. In addition, at least once per week, participant must meet 1 or more of the following:

  * History of retentive posturing or excessive volitional stool retention.
  * History of painful or hard bowel movements (BMs).
  * Presence of a large fecal mass in the rectum.
  * History of large diameter stools.
  * At least 1 episode of fecal incontinence per week after the acquisition of toileting skills, if applicable.

Exclusion Criteria:

* Participant 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 (i.e., participant reports having streaks of blood on the stool or on toilet paper and/or pain/crying with BM 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 modified Rome IV FC criteria, the participant 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
  * Childhood functional abdominal pain syndrome
  * Poorly treated or poorly controlled psychiatric disorders that might influence his or her ability to participate in the study
  * 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 Randomization (Visit 2). A complete remission is defined as the disappearance of all signs of cancer in response to treatment.)
* Has conditions that could interfere with drug absorption including but not limited to short bowel syndrome.

Primary outcomes:
measure: Change from baseline in the spontaneous bowel movement (SBM) frequency rate (SBMs/week) observed by the primary caregiver during the double-blind study intervention period.
timeFrame: Baseline to Week 12
measure: Number of Participants with Adverse Events (AEs)
timeFrame: Up to Approximately 36 Weeks
Secondary outcomes:
measure: Change from baseline in stool consistency observed by the primary caregiver during the double blind study intervention period
timeFrame: Baseline to Week 12
measure: Change from baseline in straining observed by the primary caregiver during the double-blind study intervention period
timeFrame: Baseline to Week 12
measure: Change from baseline in proportion of days with fecal incontinence during the double-blind study intervention period (for participants who have acquired toileting skills during daytime and nighttime or acquired toileting skills during daytime only)
timeFrame: Baseline to Week 12
Other outcomes:
Locations:
city: Foley
country: United States
facility: G & L Research, LLC /ID# 250658
state: Alabama
city: Phoenix
country: United States
facility: Velocity Clinical Research Phoenix /ID# 266280
state: Arizona
city: Hot Springs
country: United States
facility: HealthStar Research of Hot Springs PLLC /ID# 249481
state: Arkansas
city: Little Rock
country: United States
facility: Applied Research Center of Arkansas /ID# 249764
state: Arkansas
city: Anaheim
country: United States
facility: Advanced Research Center /ID# 249412
state: California
city: Corona
country: United States
facility: Kindred Medical Institute - Corona /ID# 249485
state: California
city: San Diego
country: United States
facility: Medical Ctr for Clin Research /ID# 254386
state: California
city: Doral
country: United States
facility: Prohealth Research Center /ID# 249420
state: Florida
city: Hollywood
country: United States
facility: KIDZ Medical Services - Hollywood /ID# 250823
state: Florida
city: Jacksonville
country: United States
facility: Nemours Children's Health System /ID# 250881
state: Florida
city: Kissimmee
country: United States
facility: Kissimmee Clinical Research /ID# 252206
state: Florida
city: Miami Springs
country: United States
facility: South Florida Research Ph I-IV /ID# 252350
state: Florida
city: Miami
country: United States
facility: South Miami Medical & Research Group Inc. /ID# 249418
state: Florida
city: Miami
country: United States
facility: Valencia Medical & Research Center /ID# 250452
state: Florida
city: Miami
country: United States
facility: Palmetto Professional Research /ID# 250875
state: Florida
city: Macon
country: United States
facility: Velocity Clinical Research Macon /ID# 266516
state: Georgia
city: Union City
country: United States
facility: Rophe Adult and Pediatric Medicine/SKYCRNG /ID# 250663
state: Georgia
city: Lexington
country: United States
facility: Michael W. Simon, MD, PSC /ID# 250664
state: Kentucky
city: Lafayette
country: United States
facility: Velocity Clinical Research - Lafayette /ID# 266751
state: Louisiana
city: New Market
country: United States
facility: Frederick County Pediatrics /ID# 249483
state: Maryland
city: Farmington Hills
country: United States
facility: Michigan Center of Medical Research /ID# 251088
state: Michigan
city: Minneapolis
country: United States
facility: MNGI Digestive Health, P. A. /ID# 249676
state: Minnesota
city: Hastings
country: United States
facility: Velocity Clinical Research- Hastings Nebraska /ID# 252132
state: Nebraska
city: Newark
country: United States
facility: Rutgers New Jersey Medical School Campus, Doctors Office Center /ID# 250876
state: New Jersey
city: Chapel Hill
country: United States
facility: Univ NC Chapel Hill /ID# 252044
state: North Carolina
city: Cleveland
country: United States
facility: UH Cleveland Medical Center /ID# 250893
state: Ohio
city: Oklahoma City
country: United States
facility: IPS Research Company /ID# 250822
state: Oklahoma
city: Scottdale
country: United States
facility: Frontier Clinical Research, LLC - Scottdale /ID# 250656
state: Pennsylvania
city: Smithfield
country: United States
facility: Frontier Clinical Research /ID# 250657
state: Pennsylvania
city: Charleston
country: United States
facility: Coastal Pediatric Research - West Ashley B /ID# 249413
state: South Carolina
city: Greenville
country: United States
facility: Tribe Clinical Research LLC /ID# 255656
state: South Carolina
city: Summerville
country: United States
facility: Coastal Pediatric Research - Summerville /ID# 249423
state: South Carolina
city: Tullahoma
country: United States
facility: Tullahoma Pediatrics /ID# 250892
state: Tennessee
city: Houston
country: United States
facility: Houston Clinical Research Associates /ID# 250779
state: Texas
city: Mansfield
country: United States
facility: Prime Clinical Research - Mansfield - East Broad Street /ID# 266236
state: Texas
city: Waxahachie
country: United States
facility: ClinPoint Trials /ID# 250448
state: Texas
city: Roanoke
country: United States
facility: Carilion Medical Center /ID# 249790
state: Virginia
city: Kingwood
country: United States
facility: Frontier Clinical Research - Kingwood /ID# 251154
state: West Virginia
city: Tsentar
country: Bulgaria
facility: University Hospital Plovdiv /ID# 250814
state: Plovdiv
city: Ruse
country: Bulgaria
facility: UMHAT Kanev /ID# 250815
city: Sofia
country: Bulgaria
facility: Acibadem City Clinic Tokuda University Hospital EAD /ID# 251234
city: Sofiya
country: Bulgaria
facility: Specialized Hospital For Active Treatment Of Children Diseases Prof. Ivan Mitev /ID# 251233
city: Varna
country: Bulgaria
facility: Nova Clinic /ID# 250816
city: Breda
country: Netherlands
facility: Amphia Ziekenhuis /ID# 251698
state: Noord-Brabant
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, locatie AMC /ID# 251295
state: Noord-Holland
city: London
country: United Kingdom
facility: Barts Health NHS Trust /ID# 251179
state: Greater London
city: Armthorpe Road
country: United Kingdom
facility: Doncaster Royal Infirmary /ID# 252080
city: Grimsby
country: United Kingdom
facility: Northern Licolnshire and Goole NHS Foundation Trust /ID# 252007
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: