Study of Choline Chloride for Injection in Adolescent and Adult Patients With Intestinal Failure Receiving Long Term Parenteral Support

Phase 2

Not yet recruiting

• Conditions: Choline Deficiency; Liver Injury
• Interventions: Drug: Choline Chloride for Injection; Drug: Placebo

• Registration Number: NCT06910943
• Lead Sponsor: Protara Therapeutics

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-03
• Study First Submitted: 2025-03-18
• Study First Submitted QC: 2025-03-27
• Last Update Submitted: 2025-03-27
• Study First Posted: 2025-04-04
• Last Update Posted: 2025-04-04
• Study Start: 2025-06
• Primary Completion: 2027-06
• Study Completion: 2028-06

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 144

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Open-Label, Dose-Selection: Dose 1	Choline Chloride for Injection	-
Open-Label, Dose-Selection: Dose 2	Choline Chloride for Injection	-
Open-Label, Dose-Selection: Dose 3	Choline Chloride for Injection	-
Double-Blind, Placebo-Controlled: High Dose	Choline Chloride for Injection	-
Double-Blind, Placebo-Controlled: Low Dose	Choline Chloride for Injection	-
Double-Blind, Placebo-Controlled: Placebo	Placebo	-
Open Label Extension: High Dose	Choline Chloride for Injection	-
Open Label Extension: Low Dose	Choline Chloride for Injection	-

Primary Outcome Measures

Name	Time	Method
Open-Label Dose-Selection Phase: Change from Baseline in plasma free choline concentrations at Week 8	Week 1 to Week 8
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)	Week 1 to Week 8	Tmax = time of maximum concentration
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)	Week 8 to Week 60
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	Week 1 to Week 60 or 76
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	Week 8 to Week 60
Open-Label Dose-Selection Phase: PK of plasma free choline (Cmax) during Week 1 and Week 8 Visits	Week 1 to Week 8	Cmax = maximum concentration
Open-Label Dose-Selection Phase: Open-Label Dose-Selection Phase: PK of plasma free choline (Tmax) during Week 1 and Week 8 Visits	Week 1 to Week 8	Tmax = time of maximum concentration
Open-Label Dose-Selection Phase: PK of plasma free choline (AUC(0-TAU)) during Week 1 and Week 8 Visits	Week 1 to Week 8	AUC = area under the curve, AUC(0-TAU) = AUC at end of dosing
Open-Label Dose-Selection Phase and Double-Blind, Placebo-Controlled Phase, Open-Label Extension Phase: Incidence and severity of TEAEs Incidence of TESAEs	Week 1 to Week 60	TEAE = treatment emergent adverse event, TESAE = treatment emergent serious adverse event
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	Week 60

Secondary Outcome Measures

Name	Time	Method
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	Week 1 to Week 60 or 76	MRI-PDFF = magnetic resonance imaging-estimated proton density fat fraction
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	Week 1 to Week 60 or 76	MRE = magnetic resonance elastography, ELF = enhanced liver fibrosis
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	Week 1 to Week 60 or 76	MRE = magnetic resonance elastography, ELF = enhanced liver fibrosis
Open-Label Extension Phase: Participants from Open-Label Dose-Selection Phase: Assessment of Quality of Life based on CLDQ at Week 60	Week 60	CLDQ = chronic liver disease questionnaire
Open-Label Extension Phase: Participants from Open-Label Dose-Selection Phase: Assessment of Quality of Life based on PGIC at Week 60	Week 60	PGIC = patient global impression of change
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	Week 60 or 76	QOL = quality of life, PGIC = patient global impression of change
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	Week 1 to Week 8	ALP = alkaline phosphatase, AST = aspartate aminotransferase, ALT = alanine transaminase, GGT = gamma-glutamyl transpeptidase, VLDL = very low-density lipoprotein, CPK = creatine phosphokinase
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	Week 1 to Week 8	QTc = QT corrected for heart rate
Open-Label Dose-Selection Phase: Percentage of participants achieving plasma free choline concentration Cmax ≥ 9.5 nmol/mL at Week 8	Week 1 to Week 8	Cmax = maximum concentration
Open-Label Dose-Selection Phase: Percentage of participants maintaining plasma free choline concentration Cmax ≥ 9.5 nmol/mL at Week 8	Week 1 to Week 8	Cmax = maximum concentration
Open-Label Dose-Selection Phase: Change from Baseline to Week 8 in height, weight and BMI	Week 1 to Week 8	BMI = body mass index Weight and height will be combined to report BMI in kg/m\^2
Open-Label Dose-Selection Phase: Percentage of participants with no worsening of steatosis from Baseline to Week 8 as measured by MRI-PDFF	Week 1 to Week 8	MRI-PDFF = magnetic resonance imaging-estimated proton density fat fraction
Open-Label Dose-Selection Phase: Percentage of participants with any improvement of steatosis from Baseline to Week 8 as measured by MRI-PDFF	Week 1 to Week 8	MRI-PDFF = magnetic resonance imaging-estimated proton density fat fraction
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)	Week 1 to Week 24	Tmax = time of maximum concentration
Double-Blind, Placebo-Controlled Phase: Percentage of participants achieving plasma free choline concentration Cmax ≥ 9.5 nmol/mL at Week 8	Week 1 to Week 8	Cmax = maximum concentration
Double-Blind, Placebo-Controlled Phase: Change from Baseline to Week 8 and Week 24 in height, weight and BMI	Week 1 to Week 24	BMI = body mass index Weight and height will be combined to report BMI in kg/m\^2
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	Week 1 to Week 24	ALP = alkaline phosphatase, AST = aspartate aminotransferase, ALT = alanine transaminase, GGT = gamma-glutamyl transpeptidase, VLDL = very low-density lipoprotein, CPK = creatine phosphokinase
Double-Blind, Placebo-Controlled Phase: Percentage of participants with no worsening of steatosis from Baseline to Week 24 as measured by MRI-PDFF	Week 1 to Week 24	MRI-PDFF = magnetic resonance imaging-estimated proton density fat fraction
Double-Blind, Placebo-Controlled Phase: Percentage of participants with any improvement of steatosis from Baseline on MRI-PDFF at Week 24	Week 1 to Week 24	MRI-PDFF = magnetic resonance imaging-estimated proton density fat fraction
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	Week 1 to Week 24	MRE = magnetic resonance elastography, ELF = enhanced liver fibrosis
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	Week 1 to Week 24	MRE = magnetic resonance elastography, ELF = enhanced liver fibrosis
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	Week 1 to Week 24	MRI-PDFF = magnetic resonance imaging-estimated proton density fat fraction, ALP = alkaline phosphatase
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	Week 1 to Week 24	MRI-PDFF = magnetic resonance imaging-estimated proton density fat fraction, ALT = alanine transaminase, AST = aspartate aminotransferase
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	Week 1 to Week 60 or 76	ALP = alkaline phosphatase, AST = aspartate aminotransferase, ALT = alanine transaminase, GGT = gamma-glutamyl transpeptidase, VLDL = very low-density lipoprotein, CPK = creatine phosphokinase, TBIL = total bilirubin, DBil = direct bilirubin
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	Week 1 to Week 60	MRI-PDFF = magnetic resonance imaging-estimated proton density fat fraction
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	Week 1 to Week 60	MRI-PDFF = magnetic resonance imaging-estimated proton density fat fraction
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	Week 1 to Week 60 or 76	MRI-PDFF = magnetic resonance imaging-estimated proton density fat fraction
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	Week 60 or 76	QOL = quality of life, CLDQ = chronic liver disease questionnaire
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)	Week 1 to Week 24	Cmax = maximum concentration
Double-Blind, Placebo-Controlled Phase: Assessment of Quality of Life based on CLDQ at Baseline and Week 24	Week 1 to Week 24	CLDQ = chronic liver disease questionnaire
Double-Blind, Placebo-Controlled Phase: Assessment of Quality of Life based on PGIC at Baseline and Week 24	Week 1 to Week 24	PGIC = patient global impression of change
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	Week 1 to Week 60	ALP = alkaline phosphatase, AST = aspartate aminotransferase, ALT = alanine transaminase, GGT = gamma-glutamyl transpeptidase, VLDL = very low-density lipoprotein, CPK = creatine phosphokinase
Open-Label Extension Phase: Participants from Open-Label Dose-Selection Phase Change from Baseline (Week 1) to Week 60 in height, weight and BMI	Week 1 to Week 60	BMI = body mass index Weight and height will be combined to report BMI in kg/m\^2
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	Week 1 to Week 60 or 76	BMI = body mass index Weight and height will be combined to report BMI in kg/m\^2