Clinical trial NCT06910943: Study of Choline Chloride for Injection in Adolescent and Adult Patients With Intestinal Failure Receiving Long Term Parenteral Support
Official title: A Phase 2b/3 Randomized Open-Label Dose-Selection Study With Open-Label Extension and Randomized Double-Blind, Placebo-Controlled Study With Open-Label Extension to Evaluate the Safety and Efficacy of Choline Chloride for Injection (Low Dose and High Dose) Versus Placebo in Adolescents and Adults With Intestinal Failure Receiving Long-Term Parenteral Support
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Choline Deficiency
Liver Injury
Keywords: Intestinal Failure
Parenteral Nutrition
Parenteral Support
Choline Chloride
choline deficiency
Lead sponsor: Protara Therapeutics
Sponsor class: INDUSTRY
First posted: 2025-04-04
Enrollment: 144
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: TARA-001-301 is a Phase 2b/3 randomized Open-Label Dose-Selection study with an Open-Label Extension and randomized Double-Blind, Placebo-Controlled Study with Open-Label Extension to investigate the safety and efficacy of Choline Chloride for Injection (Low Dose and High Dose) versus Placebo in adolescents (ages 12 to \< 18 years of age) and adults (≥ 18 years of age) with intestinal failure receiving long-term PS when oral or enteral nutrition is not possible, insufficient, or contraindicated.

Participants will be enrolled in one of 2 parts, each part will be followed by an open-label extension period of approximately a year.

Part 1: Open-Label Dose-Selection Phase Part 2: Double-Blind, Placebo-Controlled Phase

The purpose of the Open-Label Dose-Selection Phase is to evaluate the safety, tolerability, how Choline Chloride for Injection (study drug) is distributed in the body, and to select 2 of 3 doses for testing in the Double-Blind, Placebo-Controlled Phase.

The purpose of the Double-Blind, Placebo-Controlled Phase is to assess the safety of the study drug and how well the study drug works at the 2 selected dose levels.


Eligibility criteria: Key Inclusion Criteria:

* Male or female 12 years of age or older at the time of signing the informed consent
* Individuals who have voluntarily given written informed consent after the nature of the study has been explained according to applicable requirements, prior to study entry.
* Individuals with intestinal failure receiving long-term PS when oral or enteral nutrition is not possible, insufficient, or contraindicated who are receiving stable PS at time of screening and for the duration of the study; Note: Long-Term PS = Participant must have been receiving PS for at least 6 months prior to screening and requiring PS at least 3 times per week
* Females of childbearing potential must have a negative urine pregnancy test at screening

Key Exclusion Criteria:

* Patients taking steatogenic medications for ≥ 12 weeks in the past 12 months; those taking any medicine that could affect the measurement of hepatic steatosis within 12 weeks prior to study entry
* Evidence of systemic active infection at the time of dosing
* Participants intending to take non-study drug choline supplements or choline-containing multivitamins during the course of the study
* Participants unwilling to limit alcohol intake to no more than 20/g a day for 24 hours prior to their screening visit and for the duration of the study
* Active malignancy (excluding basal cell skin tumor, low or very low risk prostate cancer, cervical carcinoma in situ and local resected cervical cancer)
* Clinically significant renal disease
* Low B12 or low serum folic acid levels that are less than the normal range
* Fulminant liver failure, with active bleeding and/or encephalopathy

Primary outcomes:
measure: Open-Label Dose-Selection Phase: PK of plasma free choline (Cmax) during Week 1 and Week 8 Visits
timeFrame: Week 1 to Week 8
measure: Open-Label Dose-Selection Phase: Open-Label Dose-Selection Phase: PK of plasma free choline (Tmax) during Week 1 and Week 8 Visits
timeFrame: Week 1 to Week 8
measure: Open-Label Dose-Selection Phase: PK of plasma free choline (AUC(0-TAU)) during Week 1 and Week 8 Visits
timeFrame: Week 1 to Week 8
measure: Open-Label Dose-Selection Phase: Change from Baseline in plasma free choline concentrations at Week 8
timeFrame: Week 1 to Week 8
measure: Open-Label Dose-Selection Phase and Double-Blind, Placebo-Controlled Phase, Open-Label Extension Phase: Incidence and severity of TEAEs Incidence of TESAEs
timeFrame: Week 1 to Week 60
measure: Double-Blind, Placebo-Controlled Phase: Change from Baseline in plasma free choline concentrations at Week 8 in participants receiving Choline Chloride for Injection versus Placebo (measured at estimated Tmax)
timeFrame: Week 1 to Week 8
measure: Open-Label Extension Phase: Participants from Open-Label Dose-Selection Phase: Percentage of participants with plasma free choline concentrations of ≥ 9.5 nmol/mL at Week 60
timeFrame: Week 60
measure: Open-Label Extension Phase: Percentage of participants maintaining plasma free choline concentrations of ≥ 9.5 nmol/mL at Week 8 and Week 60 (ie, both timepoints)
timeFrame: Week 8 to Week 60
measure: Open-Label Extension Phase: Participants from Double-Blind, Placebo-Controlled Phase: % with plasma free choline concentrations of ≥9.5 nmol/mL approximately 12 months after start of treatment with Choline Chloride for Injection at Week 60 or Week 76
timeFrame: Week 1 to Week 60 or 76
measure: Open-Label Extension Phase: Participants from Double-Blind Placebo-Controlled Phase: % maintaining plasma free choline concentrations of ≥ 9.5 nmol/mL at Week 8, Week 24 and Week 60 for participants who previously received Choline Chloride for Injection
timeFrame: Week 8 to Week 60
Secondary outcomes:
measure: Open-Label Dose-Selection Phase: Change from Baseline to Week 8 in ALP, AST, ALT, GGT, VLDL, total bilirubin, direct bilirubin levels, CPK, homocysteine and albumin levels
timeFrame: Week 1 to Week 8
measure: Open-Label Dose-Selection Phase: Triplicate QTc measurements collected during Week 1 and Week 8, and changes from pre-infusion QTc at Week 1 to all post-baseline timepoints
timeFrame: Week 1 to Week 8
measure: Open-Label Dose-Selection Phase: Percentage of participants achieving plasma free choline concentration Cmax ≥ 9.5 nmol/mL at Week 8
timeFrame: Week 1 to Week 8
measure: Open-Label Dose-Selection Phase: Percentage of participants maintaining plasma free choline concentration Cmax ≥ 9.5 nmol/mL at Week 8
timeFrame: Week 1 to Week 8
measure: Open-Label Dose-Selection Phase: Change from Baseline to Week 8 in height, weight and BMI
timeFrame: Week 1 to Week 8
measure: Open-Label Dose-Selection Phase: Percentage of participants with no worsening of steatosis from Baseline to Week 8 as measured by MRI-PDFF
timeFrame: Week 1 to Week 8
measure: Open-Label Dose-Selection Phase: Percentage of participants with any improvement of steatosis from Baseline to Week 8 as measured by MRI-PDFF
timeFrame: Week 1 to Week 8
measure: Double-Blind, Placebo-Controlled Phase: Change from Baseline and Week 8 in plasma free choline concentrations at Week 24 in participants receiving Choline Chloride for Injection versus Placebo (measured at estimated Tmax)
timeFrame: Week 1 to Week 24
measure: Double-Blind, Placebo-Controlled Phase: Percentage of participants achieving plasma free choline concentration Cmax ≥ 9.5 nmol/mL at Week 8
timeFrame: Week 1 to Week 8
measure: Double-Blind, Placebo-Controlled Phase: Percentage of participants maintaining plasma free choline concentration Cmax ≥ 9.5 nmol/mL at Week 8 and Week 24 (ie, through Week 24)
timeFrame: Week 1 to Week 24
measure: Double-Blind, Placebo-Controlled Phase: Change from Baseline to Week 8 and Week 24 in height, weight and BMI
timeFrame: Week 1 to Week 24
measure: Double-Blind, Placebo-Controlled Phase: Change from Baseline to Week 8 and Week 24 in ALP, AST, ALT, GGT, VLDL, total bilirubin, direct bilirubin levels, CPK, homocysteine and albumin levels
timeFrame: Week 1 to Week 24
measure: Double-Blind, Placebo-Controlled Phase: Percentage of participants with no worsening of steatosis from Baseline to Week 24 as measured by MRI-PDFF
timeFrame: Week 1 to Week 24
measure: Double-Blind, Placebo-Controlled Phase: Percentage of participants with any improvement of steatosis from Baseline on MRI-PDFF at Week 24
timeFrame: Week 1 to Week 24
measure: Double-Blind, Placebo-Controlled Phase: Percentage of participants with no worsening in fibrosis grade from Baseline to Week 24, as measured by MRE and ELF test
timeFrame: Week 1 to Week 24
measure: Double-Blind, Placebo-Controlled Phase: Percentage of participants with improvement in fibrosis grade from Baseline to Week 24, as measured by MRE and ELF test
timeFrame: Week 1 to Week 24
measure: Double-Blind, Placebo-Controlled Phase: Percentage of participants with improvement of steatosis from Baseline on MRI-PDFF with improvement of ALP from Baseline to Week 24
timeFrame: Week 1 to Week 24
measure: Double-Blind, Placebo-Controlled Phase: Percentage of participants with improvement of steatosis from Baseline on MRI-PDFF with improvement of ALT or AST from Baseline to Week 24
timeFrame: Week 1 to Week 24
measure: Double-Blind, Placebo-Controlled Phase: Assessment of Quality of Life based on CLDQ at Baseline and Week 24
timeFrame: Week 1 to Week 24
measure: Double-Blind, Placebo-Controlled Phase: Assessment of Quality of Life based on PGIC at Baseline and Week 24
timeFrame: Week 1 to Week 24
measure: Open-Label Extension Phase: Participants from Open-Label Dose-Selection Phase: Change from Baseline (Week 1) to Week 60 in ALP, AST, ALT, GGT, VLDL, total bilirubin, direct bilirubin levels, CPK, homocysteine and albumin levels
timeFrame: Week 1 to Week 60
measure: Open-Label Extension Phase: Double-Blind, Placebo-Controlled Phase: Change from W1 to W60 in Choline Chloride for Injection group, and change from W24 to W76 in Placebo group in ALP, AST, ALT, GGT, VLDL, TBIL, DBil levels, CPK, homocysteine and albumin
timeFrame: Week 1 to Week 60 or 76
measure: Open-Label Extension Phase: Participants from Open-Label Dose-Selection Phase Change from Baseline (Week 1) to Week 60 in height, weight and BMI
timeFrame: Week 1 to Week 60
measure: Open-Label Extension Phase: Participants from Double-Blind, Placebo-Controlled Phase: Change from W1 to W60 for participants in Choline Chloride for Injection group, and change from W24 to W76 for participants in Placebo group in height, weight and BMI
timeFrame: Week 1 to Week 60 or 76
measure: Open-Label Extension Phase: Participants from Open-Label Dose-Selection Phase: Percentage of participants with no worsening of steatosis as measured by MRI-PDFF from Baseline (Week 1) to Week 60
timeFrame: Week 1 to Week 60
measure: Open-Label Extension Phase: Participants from Open-Label Dose-Selection Phase: Percentage of participants with improvement of steatosis as measured by MRI-PDFF from Baseline (Week 1) to Week 60
timeFrame: Week 1 to Week 60
measure: Open-Label Extension Phase: Participants from Double-Blind, Placebo-Controlled Phase: % of participants with no worsening of steatosis measured by MRI-PDFF from W1 to W60 in Choline Chloride for Injection group, and from W24 to W76 in Placebo group
timeFrame: Week 1 to Week 60 or 76
measure: Open-Label Extension Phase: Participants from Double-Blind, Placebo-Controlled Phase: % of participants with improvement of steatosis measured by MRI-PDFF from W1 to W60 in Choline Chloride for Injection group, and from W24 to W76 in Placebo group
timeFrame: Week 1 to Week 60 or 76
measure: Open-Label Extension Phase: Double-Blind, Placebo-Controlled Phase: % of participants with no worsening in fibrosis grade measured by MRE and ELF test from W1 to W60 in Choline Chloride for Injection group, and from W24 to W76 in Placebo group
timeFrame: Week 1 to Week 60 or 76
measure: Open-Label Extension Phase: Participants from Double-Blind, Placebo-Controlled Phase: % of participants with improvement in fibrosis measured by MRE and ELF test from W1 to W60 in Choline Chloride for Injection group, and W24 to W76 in Placebo group
timeFrame: Week 1 to Week 60 or 76
measure: Open-Label Extension Phase: Participants from Open-Label Dose-Selection Phase: Assessment of Quality of Life based on CLDQ at Week 60
timeFrame: Week 60
measure: Open-Label Extension Phase: Participants from Open-Label Dose-Selection Phase: Assessment of Quality of Life based on PGIC at Week 60
timeFrame: Week 60
measure: Open-Label Extension Phase: Participants from Double-Blind Placebo-Controlled Phase: Assessment of QOL based on CLDQ at Week 60 for participants who previously received Choline Chloride for Injection, and Week 76 for participants who received Placebo
timeFrame: Week 60 or 76
measure: Open-Label Extension Phase: Participants from Double-Blind Placebo-Controlled Phase: Assessment of QOL based on PGIC at Week 60 for participants who previously received Choline Chloride for Injection, and Week 76 for participants who received Placebo
timeFrame: Week 60 or 76
Other outcomes:
Locations:
Study officials:
affiliation: Protara Therapeutics
name: Chief Scientific Operations Officer
role: STUDY_DIRECTOR
References: