Use of Tirosint®-SOL or Tablet Formulations of Levothyroxine in Pediatric Patients With Congenital Hypothyroidism (CH)

A Randomized Comparative Study Between Liquid (Tirosint®-SOL) and Tablet Formulations of Levothyroxine in Neonates and Infants With Congenital Hypothyroidism

This is a multi-center, prospective, parallel-group, open-label, randomized clinical study in one hundred and twenty-six (126) neonates and infants diagnosed with CH.

Subjects will be randomized in a 2:1 ratio to Treatment (Tirosint®-SOL) or Control (conventional therapy with levothyroxine sodium crushed tablets).

Study Overview

• Status: Active, not recruiting
• Conditions: Congenital Hypothyroidism
• Intervention / Treatment: Drug: Tirosint®-SOL; Drug: Levothyroxine Sodium

Detailed Description

Newly diagnosed neonates will be randomly assigned to start therapy with LT4 at the initial dose recommended by the Standard of Care (SOC). Infants already on LT4 therapy will continue at the same daily dose within the randomly assigned treatment group (dose adjustments are allowed, if needed based on laboratory parameters and clinical response). Once enrolled, subjects will be treated and followed for 12 months (±1.5 months), participating in 7-8 study visits, consisting of 6-7 inclinic and 1-2 (or more if follow-up visits are required) telemedicine (TM) visits. The total number of visits depends on the age at inclusion.

• Study Type: Interventional
• Enrollment (Estimated): 126
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital of Los Angeles
    • Orange, California, United States, 92868
      • CHOC Children's Hospital
    • San Francisco, California, United States, 94143
      • University of California San Francisco
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale University
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Children's Hospital of Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital of Chicago
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Children's Mercy Hospital and Clinics
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Children's Hospital Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Health Care Systems

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 9 months (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male and female patient aged 0 to 9 months

• Primary CH diagnosis with elevated TSH and low or normal FT4, requiring treatment with LT4, under either of the following conditions:

  • Neonates newly diagnosed with primary CH and needing to initiate LT4 therapy, or
  • Infants previously diagnosed with primary CH and who are already on LT4 therapy for at least 3 weeks;
• Provide and comply with the informed consent.

Exclusion Criteria:

• Preterm neonates with a gestational age < 37 weeks;
• Low birth weight (LBW) or very low birth weight (VLBW) neonates (weight < 2.5 kg) or VLBW infants (weight < 1.5 kg);
• Neonates in neonatal intensive care units or requiring admission to NICU or neonates/infants hospitalized or requiring hospitalization or in fragile health conditions (e.g. with serious health problems or complications);
• Neonates with CH diagnosis > 4 weeks after delivery;

• Diagnosis of primary gastrointestinal disease:

  • Gastroesophageal reflux requiring medical therapy (beyond thickening of formula or position);
  • Anatomic defects (e.g. intestinal atresia, malrotation, tracheoesophageal fistula, pyloric stenosis, Hirschsprung's disease, gastroschisis);
  • Dietary allergy (e.g. cow's milk protein allergy);
  • Malabsorption related to cystic fibrosis, celiac disease and others;
  • Necrotizing enterocolitis requiring surgical resection;
• Known or suspected adrenal insufficiency (e.g. congenital adrenal hyperplasia, hypopituitarism);
• Diagnosis of congenital cardiac disease, cardiac insufficiency or risk for cardiac failure;
• Diagnosis of chromosomopathy;
• Diagnosis of central hypothyroidism;
• Hypersensitivity to glycerol;
• Concomitant anticonvulsant medications, liothyronine, combination of LT4 and liothyronine, thyroid extracts and/or chronic or long-term use of systemic glucocorticoids
• History of nonadherence with medication or medical visit schedule; or
• Any condition for which, participation would not be in the best interest of the patient or that could limit protocol specified assessments.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control; Crushed levothyroxine sodium tablets	Drug: Levothyroxine Sodium; Tablets will be crushed and dissolved in solution. Dosage will be according to the USPI and Standard of Care.; Other Names: levothyroxine sodium tablets
Experimental: Treatment; Tirosint®-SOL (levothyroxine sodium) oral solution (IBSA Pharma Inc.) at the following strengths: 13, 25, 37.5, 44, 50, 62.5, 75, 88, 100 mcg.	Drug: Tirosint®-SOL; Dosage will be according to the USPI and Standard of Care.; Other Names: levothyroxine sodium oral solution (liquid)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LT4 dose required to maintain TSH in target range (unit: mcg/kg/day)	The LT4 dose is calculated based on the daily LT4 dose (mcg) used in the time period preceding the visit (or the average daily dose on a weekly basis if more than one strength is used over the course of the week) and the body weight (kg) measured during the visit.	Up to 22 months based on age group

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of dose adjustments	Percent number of subjects (%) who need a dose adjustment in the long-term follow up phase	Up to 22 months based on age group
Hormonal profile for TSH	TSH (unit mU/L)	Up to 22 months based on age group
Hormonal profile for FT4	FT4 (unit ng/dL)	Up to 22 months based on age group
Number of events of TSH values above 4.5 mU/L	TSH value above 4.5 mU/L	Up to 22 months based on age group
Number of events of FT4 values below the middle of the laboratory normal range	FT4 value below the middle of the laboratory normal range	Up to 22 months based on age group
Growth pattern for length of body	Subject growth measurements in Length (cm) of body	Up to 22 months based on age group
Growth pattern for body weight	Subject growth measurements in Body weight (kg)	Up to 22 months based on age group
Growth pattern for head circumference	Subject growth measurements in Head circumference (cm)	Up to 22 months based on age group
Parent/caregiver reports of satisfaction and ease of administration	Parents Satisfaction Questionnaire is a study-specific tool measuring coping and mental well-being and satisfaction Score: 1-Strongly disagree, 2-Disagree, 3-Neutral, 4-Agree, 5-Strongly agree.	Up to 22 months based on age group
Subject acceptance of the treatment (CareCAT)	Caregiver Administered Children's Acceptance Tool (CareCAT) is a 5-point nominal scale used to assess the acceptance of oral medicines in infants and toddlers who are unable to verbally give their opinion about a medicine	Up to 22 months based on age group
Signs and symptoms of hypothyroidism	Total number of subjects experiencing hypothyroidism's signs and symptoms	Up to 22 months based on age group
Signs and symptoms of hyperthyroidism	Total number of subjects experiencing hyperthyroidism's signs and symptoms	Up to 22 months based on age group

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to normalize TSH in neonates	Time to normalize TSH into reference range (unit: days)	Up to 28 days
Time to normalize FT4 in neonates	Time to normalize FT4 into the upper half of the laboratory normal FT4 range (unit: days)	Up to 28 days

Collaborators and Investigators

• Sponsor: IBSA Institut Biochimique SA
• Collaborators: Cromsource
• Investigators: Study Director: Giuseppe Mautone, IBSA Head of R&D Scientific Affairs

Study record dates

Study Major Dates

• Study Start (Actual): January 21, 2022
• Primary Completion (Estimated): April 30, 2025
• Study Completion (Estimated): April 30, 2025

Study Registration Dates

• First Submitted: December 21, 2021
• First Submitted That Met QC Criteria: January 27, 2022
• First Posted (Actual): February 8, 2022

Study Record Updates

• Last Update Posted (Estimated): April 15, 2024
• Last Update Submitted That Met QC Criteria: April 12, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Genetic Diseases, Inborn; Musculoskeletal Diseases; Thyroid Diseases; Bone Diseases; Bone Diseases, Endocrine; Dwarfism; Bone Diseases, Developmental; Hypothyroidism; Congenital Hypothyroidism
• Other Study ID Numbers: 20US-T414

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No