Study of Choline Chloride for Injection in Adolescent and Adult Patients With Intestinal Failure Receiving Long Term Parenteral Support (THRIVE-3)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Liver Injury; Choline Deficiency
• Intervention / Treatment: Drug: Choline Chloride for Injection; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 129
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Chief Scientific Operations Officer; Phone Number: 16468440337; Email: clinicaltrials@protaratx.com

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Recruiting
    • University Hospitals Leuven, Campus Gasthuisberg
    • Contact: Use Central Contact
• Denmark
  • Aalborg, Denmark, 9100
    • Recruiting
    • Aalborg University Hospital, Department of Medical Gastroenterology
    • Contact: Use Central Contact
  • Copenhagen, Denmark, 2100
    • Recruiting
    • Rigshospitalet - University Hospital Copenhagen
    • Contact: Use Central Contact
• France
  • Clichy, France, 92110
    • Not yet recruiting
    • Beaujon Hospital - APHP
    • Contact: Use Central Contact
  • Rennes, France, 35000
    • Not yet recruiting
    • Rennes University Hospital Center - Pontchaillou Site
    • Contact: Use Central Contact
  • Vandœuvre-lès-Nancy, France, 54511
    • Not yet recruiting
    • CHRU Nancy - Barbois Hospital
    • Contact: Use Central Contact
• Germany
  • Berlin, Germany, 13353
    • Recruiting
    • Charite - University Hospital Berlin
    • Contact: Use Central Contact
  • Essen, Germany, 45147
    • Not yet recruiting
    • University Duisburg-Essen, University Hospital Essen
    • Contact: Use Central Contact
• Poland
  • Lodz, Poland, 90-532
    • Recruiting
    • M. Pirogow Provincial Specialized Hospital in Lodz, Nutritional Treatment Center
    • Contact: Use Central Contact
  • Warsaw, Poland, 00-739
    • Recruiting
    • Czerniakowski Hospital Sp. z o.o. (LCC)
    • Contact: Use Central Contact
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado School of Medicine
      • Contact: Use Central Contact
  • Florida
    • Miami Lakes, Florida, United States, 33016
      • Recruiting
      • Floridian Clinical Research
      • Contact: Use Central Contact
  • Nebraska
    • Omaha, Nebraska, United States, 68105
      • Not yet recruiting
      • Nebraska Medicine
      • Contact: Use Central Contact
  • New York
    • New York, New York, United States, 10032
      • Not yet recruiting
      • Columbia University Medical Center/ New York Presbyterian Hospital
      • Contact: Use Central Contact
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke Clinic - Abdominal Transplant Research Office
      • Contact: Use Central Contact
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic
      • Contact: Use Central Contact
  • Texas
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • Pinnacle Clinical Research- San Antonio
      • Contact: Use Central Contact

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Open-Label, Dose-Selection: Dose 1	Drug: Choline Chloride for Injection; Intravenous use
Experimental: Open-Label, Dose-Selection: Dose 2	Drug: Choline Chloride for Injection; Intravenous use
Experimental: Open-Label, Dose-Selection: Dose 3	Drug: Choline Chloride for Injection; Intravenous use
Experimental: Double-Blind, Placebo-Controlled: High Dose	Drug: Choline Chloride for Injection; Intravenous use
Experimental: Double-Blind, Placebo-Controlled: Low Dose	Drug: Choline Chloride for Injection; Intravenous use
Placebo Comparator: Double-Blind, Placebo-Controlled: Placebo	Drug: Placebo; Intravenous use
Experimental: Open Label Extension: High Dose	Drug: Choline Chloride for Injection; Intravenous use
Experimental: Open Label Extension: Low Dose	Drug: Choline Chloride for Injection; Intravenous use

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Open-Label Dose-Selection Phase: PK of plasma free choline (Cmax) during Week 1 and Week 8 Visits	Cmax = maximum concentration	Week 1 to Week 8
Open-Label Dose-Selection Phase: Open-Label Dose-Selection Phase: PK of plasma free choline (Tmax) during Week 1 and Week 8 Visits	Tmax = time of maximum concentration	Week 1 to Week 8
Open-Label Dose-Selection Phase: PK of plasma free choline (AUC(0-TAU)) during Week 1 and Week 8 Visits	AUC = area under the curve, AUC(0-TAU) = AUC at end of dosing	Week 1 to Week 8
Open-Label Dose-Selection Phase: Change from Baseline in plasma free choline concentrations at Week 8		Week 1 to Week 8
Open-Label Dose-Selection Phase and Double-Blind, Placebo-Controlled Phase, Open-Label Extension Phase: Incidence and severity of TEAEs Incidence of TESAEs	TEAE = treatment emergent adverse event, TESAE = treatment emergent serious adverse event	Week 1 to Week 64
Double-Blind, Placebo-Controlled Phase: Change from Baseline in peak plasma free choline concentrations (Cmax) at Week 8 in participants receiving Choline Chloride for Injection versus Placebo	Tmax = time of maximum concentration	Week 1 to Week 8
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 64		Week 64
Open-Label Extension Phase: Percentage of participants maintaining plasma free choline concentrations of ≥ 9.5 nmol/mL at Week 8 and Week 64 (ie, both timepoints)		Week 8 to Week 64
Open-Label Extension Phase: Participants from Double-Blind, Placebo-Controlled Phase: % with plasma free choline concentrations of ≥9.5 nmol/mL at Week 64		Week 1 to Week 64
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 64 for participants who previously received Choline Chloride for Injection		Week 8 to Week 64

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	ALP = alkaline phosphatase, AST = aspartate aminotransferase, ALT = alanine transaminase, GGT = gamma-glutamyl transpeptidase, VLDL = very low-density lipoprotein, CPK = creatine phosphokinase	Week 1 to Week 8
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	QTc = QT corrected for heart rate	Week 1 to Week 8
Open-Label Dose-Selection Phase: Percentage of participants achieving plasma free choline concentration Cmax ≥ 9.5 nmol/mL at Week 8	Cmax = maximum concentration	Week 1 to Week 8
Open-Label Dose-Selection Phase: Percentage of participants maintaining plasma free choline concentration Cmax ≥ 9.5 nmol/mL at Week 8	Cmax = maximum concentration	Week 1 to Week 8
Open-Label Dose-Selection Phase: Change from Baseline to Week 8 in height, weight and BMI	BMI = body mass index Weight and height will be combined to report BMI in kg/m^2	Week 1 to Week 8
Open-Label Dose-Selection Phase: Percentage of participants with no worsening of steatosis from Baseline to Week 8 as measured by MRI-PDFF	MRI-PDFF = magnetic resonance imaging-estimated proton density fat fraction	Week 1 to Week 8
Open-Label Dose-Selection Phase: Percentage of participants with any improvement of steatosis from Baseline to Week 8 as measured by MRI-PDFF	MRI-PDFF = magnetic resonance imaging-estimated proton density fat fraction	Week 1 to Week 8
Double-Blind, Placebo-Controlled Phase: Percentage of participants achieving plasma free choline concentration Cmax ≥ 9.5 nmol/mL at Week 8	Cmax = maximum concentration	Week 1 to Week 8
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)	Cmax = maximum concentration	Week 1 to Week 24
Double-Blind, Placebo-Controlled Phase: Change from Baseline to Week 8 and Week 24 in height, weight and BMI	BMI = body mass index Weight and height will be combined to report BMI in kg/m^2	Week 1 to Week 24
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	ALP = alkaline phosphatase, AST = aspartate aminotransferase, ALT = alanine transaminase, GGT = gamma-glutamyl transpeptidase, VLDL = very low-density lipoprotein, CPK = creatine phosphokinase	Week 1 to Week 24
Double-Blind, Placebo-Controlled Phase: Percentage of participants with no worsening of steatosis from Baseline to Week 24 as measured by MRI-PDFF	MRI-PDFF = magnetic resonance imaging-estimated proton density fat fraction	Week 1 to Week 24
Double-Blind, Placebo-Controlled Phase: Percentage of participants with any improvement of steatosis from Baseline on MRI-PDFF at Week 24	MRI-PDFF = magnetic resonance imaging-estimated proton density fat fraction	Week 1 to Week 24
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	MRE = magnetic resonance elastography, ELF = enhanced liver fibrosis	Week 1 to Week 24
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	MRE = magnetic resonance elastography, ELF = enhanced liver fibrosis	Week 1 to Week 24
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	MRI-PDFF = magnetic resonance imaging-estimated proton density fat fraction, ALP = alkaline phosphatase	Week 1 to Week 24
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	MRI-PDFF = magnetic resonance imaging-estimated proton density fat fraction, ALT = alanine transaminase, AST = aspartate aminotransferase	Week 1 to Week 24
Double-Blind, Placebo-Controlled Phase: Assessment of Quality of Life based on CLDQ at Baseline and Week 24	CLDQ = chronic liver disease questionnaire	Week 1 to Week 24
Double-Blind, Placebo-Controlled Phase: Change from Baseline and Week 8 in peak plasma free choline concentrations (Cmax) at Week 24 in participants receiving Choline Chloride for Injection versus Placebo	Tmax = time of maximum concentration	Week 1 to Week 24
Double-Blind, Placebo-Controlled Phase: Assessment of Quality of Life based on PGIS at Baseline and PGIC at Week 24	PGIC = patient global impression of change	Week 1 to Week 24
Open-Label Extension Phase: Participants from Open-Label Dose-Selection Phase: Change from Baseline (Week 1) to Week 64 in ALP, AST, ALT, GGT, VLDL, total bilirubin, direct bilirubin levels, CPK, homocysteine and albumin levels	ALP = alkaline phosphatase, AST = aspartate aminotransferase, ALT = alanine transaminase, GGT = gamma-glutamyl transpeptidase, VLDL = very low-density lipoprotein, CPK = creatine phosphokinase	Week 1 to Week 64
Open-Label Extension Phase: Double-Blind, Placebo-Controlled Phase: Change from W1 to W64 in Choline Chloride for Injection group, and change from W24 to W64 in Placebo group in ALP, AST, ALT, GGT, VLDL, TBIL, DBil levels, CPK, homocysteine and albumin	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	Week 1 to Week 64
Open-Label Extension Phase: Participants from Open-Label Dose-Selection Phase Change from Baseline (Week 1) to Week 64 in height, weight and BMI	BMI = body mass index Weight and height will be combined to report BMI in kg/m^2	Week 1 to Week 64
Open-Label Extension Phase: Participants from Double-Blind, Placebo-Controlled Phase: Change from W1 to W64 for participants in Choline Chloride for Injection group, and change from W24 to W64 for participants in Placebo group in height, weight and BMI	BMI = body mass index Weight and height will be combined to report BMI in kg/m^2	Week 1 to Week 64
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 64	MRI-PDFF = magnetic resonance imaging-estimated proton density fat fraction	Week 1 to Week 64
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 64	MRI-PDFF = magnetic resonance imaging-estimated proton density fat fraction	Week 1 to Week 64
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 W64 in Choline Chloride for Injection group, and from W24 to W64 in Placebo group	MRI-PDFF = magnetic resonance imaging-estimated proton density fat fraction	Week 1 to Week 64
Open-Label Extension Phase: Participants from Double-Blind, Placebo-Controlled Phase: % of participants with improvement of steatosis measured by MRI-PDFF from W1 to W64 in Choline Chloride for Injection group, and from W24 to W64 in Placebo group	MRI-PDFF = magnetic resonance imaging-estimated proton density fat fraction	Week 1 to Week 64
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 W64 in Choline Chloride for Injection group, and from W24 to W64 in Placebo group	MRE = magnetic resonance elastography, ELF = enhanced liver fibrosis	Week 1 to Week 64
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 W64 in Choline Chloride for Injection group, and W24 to W64 in Placebo group	MRE = magnetic resonance elastography, ELF = enhanced liver fibrosis	Week 1 to Week 64
Open-Label Extension Phase: Participants from Double-Blind Placebo-Controlled Phase: Assessment of QOL based on CLDQ at Week 64	QOL = quality of life, CLDQ = chronic liver disease questionnaire	Week 64
Open-Label Extension Phase: Participants from Double-Blind Placebo-Controlled Phase: Assessment of QOL based on PGIC at Week 64	QOL = quality of life, PGIC = patient global impression of change	Week 64

Collaborators and Investigators

• Sponsor: Protara Therapeutics
• Investigators: Study Director: Chief Scientific Operations Officer, Protara Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: March 18, 2025
• First Submitted That Met QC Criteria: March 27, 2025
• First Posted (Actual): April 4, 2025

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 14, 2026
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Parenteral Nutrition; Intestinal Failure; Parenteral Support; Choline Chloride; choline deficiency
• Additional Relevant MeSH Terms: Nutrition Disorders; Signs and Symptoms, Digestive; Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Avitaminosis; Deficiency Diseases; Malnutrition; Vitamin B Deficiency; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Intestinal Failure; Hyperphagia; Choline Deficiency; Organic Chemicals; Therapeutics; Drug Administration Routes; Drug Therapy; Amines; Alcohols; Amino Alcohols; Ethanolamines; Quaternary Ammonium Compounds; Onium Compounds; Trimethyl Ammonium Compounds; Choline; Injections
• Other Study ID Numbers: TARA-001-301

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