CHOLINE CHLORIDE for Intestinal failure

Inclusion criteria

• {"criterion_text":"- 1. Male or female 12 years of age or older at the time of signing the informed consent. Adolescent (12 to <18 year of age) participants will not be enrolled in Denmark, France, or Poland.\n- 2. Individuals or their parents/legally authorized representatives (LARs) who have voluntarily given written informed consent and participants who provided assent (if applicable) after the nature of the study has been explained according to applicable requirements, prior to study entry. Parent(s)/LAR(s) may provide written consent if the participant is under the age of 18. Written assent from adolescents is applicable if required per local regulations.\n- 3. 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 (ie, signing of ICF) and for the duration of the study • Receiving a stable amount of lipid emulsion, dextrose, amino acids at least 4 weeks prior to screening • Receiving B12 and folic acid\n- 4. Females of childbearing potential must have a negative urine pregnancy test at screening"}

Exclusion criteria

• {"criterion_text":"- 1. Participants taking steatogenic medications for ≥ 12 weeks in the past 12 months (eg, amiodarone, tamoxifen, methotrexate, tetracycline, glucocorticoids, anabolic steroids, over the usual dose of estrogen for hormone replacement therapy, and valproate); those taking any medicine (eg, metformin, thiazolidinediones, ursodeoxycholic acid, pentoxifylline, S-adenosyl-L-Methionine, betaine, and resmetirom) that could affect the measurement of hepatic steatosis within 12 weeks prior to study entry\n- 9. Fulminant liver failure, with active bleeding and/or encephalopathy. “A CTP class C” would be acceptable if there was no active bleeding or encephalopathy impairing ability to give consent\n- 11. Planned surgery during the study period (eg. bowel resection or fistula repair)\n- 12. Concurrent or planned therapy which, in the opinion of the Investigator, interferes with the participant’s ability to complete participation in the study or produce evaluable data\n- 13. Any reason which, in the opinion of the Principal Investigator (PI), would make participation in the study against the participant’s best interests\n- 10. Participation in an interventional clinical study with drugs within 6 weeks prior to screening\n- 2. Evidence of systemic active infection at the time of dosing\n- 3. Participants intending to take non-study intervention choline supplements or choline-containing multivitamins during the course of the study\n- 4. 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\n- 5. Women who are nursing, pregnant or intending to become pregnant during the study\n- 6. Active malignancy (excluding basal cell skin tumor, low or very low risk prostate cancer, cervical carcinoma in situ and local resected cervical cancer)\n- 7. Clinically significant renal disease (defined as estimated glomerular filtration rate [eGFR] ≤ 30 mL/min/1.73 m²)\n- 8. Low B12 or low serum folic acid levels that are less than the normal range"}

Primary endpoints

• {"endpoint_text":"- Dose-Selection (DS) 1. Non-compartmental plasma free choline PK parameters during Week 1 and Week 8 Visits, and changes in PK parameters from Baseline to Week 8\n- Dose-Selection (DS) 2. Change from Baseline in time-matched plasma free choline concentrations at Week 8\n- Dose-Selection (DS) 3. Safety: Incidence and severity of TEAEs; Incidence of TESAEs\n- Double-Blind (DB) 1. Change from Baseline in peak plasma free choline concentrations at Week 8 in participants receiving Choline Chloride for Injection versus Placebo\n- Double-Blind (DB) 2. Safety: Incidence and severity of TEAEs; Incidence of TESAEs\n- Open-Label (OL) 1. Percentage of participants with plasma free choline concentrations of ≥ 9.5 nmol/mL at Week 64 ; Percentage of participants maintaining plasma free choline concentrations of ≥ 9.5 nmol/mL at Week 8 (, Week 24 depending on cohort) and Week 64\n- Open-Label (OL) 2. Safety: Incidence and severity of TEAEs; Incidence of TESAEs","definition_or_measurement_approach":"DS 1: Non-compartmental PK analysis of plasma free choline at Week 1 and Week 8; changes from Baseline to Week 8. DS 2: Change from Baseline in time-matched plasma free choline concentrations at Week 8. DS 3 / DB 2 / OL 2: Safety assessed by incidence and severity reporting of TEAEs and TESAEs. DB 1: Between-group comparison of change from Baseline in peak plasma free choline concentrations at Week 8 (Choline Chloride vs Placebo). OL 1: Proportion of participants achieving and maintaining plasma free choline ≥ 9.5 nmol/mL at specified weeks (Week 8/24/64) as measured by plasma assays."}

Secondary endpoints

• {"endpoint_text":"- Dose-Selection (DS) 1. Change from Baseline to Week 8 in ALP, AST, ALT, GGT, VLDL, total bilirubin, and direct bilirubin levels; Change from Baseline to Week 8 in CPK levels; Change from Baseline to Week 8 in homocysteine and albumin levels\n- Dose-Selection (DS) 2. Triplicate QTc measurements collected during Week 1 and Week 8, and changes from pre-infusion QTc at Week 1 to all post-baseline timepoints\n- Dose-Selection (DS) 3. Percentage of participants achieving plasma free choline concentration Cmax ≥ 9.5 nmol/mL at Week 8\n- Dose-Selection (DS) 4. Percentage of participants maintaining plasma free choline concentration Cmax ≥ 9.5 nmol/mL at Week 8\n- Dose-Selection (DS) 5. Change from Baseline to Week 8 in height, weight, and BMI\n- Dose-Selection (DS) 6. Percentage of participants with no worsening of steatosis from Baseline to Week 8 as measured by MRI-PDFF; Percentage of participants with any improvement of steatosis from Baseline to Week 8 as measured by MRI-PDFF\n- Double-Blind (DB) 1. Change from Baseline and Week 8 in peak plasma free choline concentrations at Week 24 in participants receiving Choline Chloride for Injection versus Placebo\n- Double-Blind (DB) 2. Percentage of participants achieving plasma free choline concentration Cmax ≥ 9.5 nmol/mL at Week 8\n- Double-Blind (DB) 3. Percentage of participants maintaining plasma free choline concentration Cmax ≥ 9.5 nmol/mL at Week 8 and Week 24 (ie, through Week 24)\n- Double-Blind (DB) 4. Change from Baseline to Week 8 and Week 24 in height, weight, and BMI\n- Double-Blind (DB) 5. Change from Baseline to Week 8 and Week 24 in ALP, AST, ALT, GGT, VLDL, total bilirubin, and direct bilirubin levels; Change from Baseline to Week 8 and Week 24 in CPK levels ; Change from Baseline to Week 8 and Week 24 in homocysteine and albumin levels\n- Double-Blind (DB) 6a. Percentage of participants with no worsening of steatosis from Baseline to Week 24 as measured by MRI-PDFF; Percentage of participants with any improvement of steatosis from Baseline on MRI-PDFF at Week 24; Percentage of participants with no worsening in fibrosis grade from Baseline to Week 24, as measured by MRE and ELF test\n- Double-Blind (DB) 6b. Percentage of participants with improvement in fibrosis grade from Baseline to Week 24, as measured by MRE and ELF test; Percentage of participants with improvement of steatosis from Baseline on MRI-PDFF with improvement of ALP from Baseline to Week 24; Percentage of participants with improvement of steatosis from Baseline on MRI-PDFF with improvement of ALT or AST from Baseline to Week 24\n- Double-Blind (DB) 7. Assessment of Quality of Life based on CLDQ at Baseline and Week 24; Assessment of Quality of Life based on PGIS at Baseline and PGIC at Week 24\n- Open-Label (OL) 1. Change from Baseline (Week 1 for Dose-Selection Phase) (Week 1 or Week 24 for Double-Blind Phase) to Week 64 in ALP, AST, ALT, GGT, VLDL, total bilirubin, and direct bilirubin levels; Change from Baseline (Week 1 for Dose-Selection Phase) (Week 1 or Week 24 for Double-Blind Phase) to Week 64 in CPK levels; Change from Baseline (Week 1 for Dose-Selection Phase) (Week 1 or Week 24 for Double-Blind Phase) to Week 64 in in homocysteine and albumin levels\n- Open-Label (OL) 2. Change from Baseline (Week 1 for Dose-Selection Phase) (Week 1 or 24 for Double-Blind Phase) to Week 64 in height, weight and BMI\n- Open-Label (OL) 3a. Percentage of participants with no worsening of steatosis as measured by MRI-PDFF from Baseline (Week 1 for Dose-Selection Phase) (Week 1 or 24 for Double-Blind Phase) to Week 64; Percentage of participants with improvement of steatosis as measured by MRI-PDFF from Baseline (Week 1 for Dose-Selection Phase) (Week1 or 24 for Double-Blind Phase) to Week 64;\n- Open-Label (OL) 3b. Percentage of participants with no worsening in fibrosis grade as measured by MRE and ELF test from Baseline (Week 1 or 24 for Double-Blind Phase) to Week 64; Percentage of participants with improvement in fibrosis grade as measured by MRE and ELF test from Baseline (Week 1 or 24 for Double-Blind Phase) to Week 64\n- Open-Label (OL) 4. Assessment of Quality of Life based on CLDQ at Week 64 for Double-Blind Phase; Assessment of Quality of Life based on PGIC at Week 64 for Double-Blind Phase","definition_or_measurement_approach":"Secondary endpoints include laboratory biomarker changes (ALP, AST, ALT, GGT, VLDL, bilirubins, CPK, homocysteine, albumin) measured at specified weeks versus Baseline; triplicate QTc measures and changes from pre-infusion; proportions achieving or maintaining plasma free choline Cmax ≥ 9.5 nmol/mL; MRI-PDFF, MRE and ELF test measures to evaluate steatosis and fibrosis; anthropometrics (height, weight, BMI); and patient-reported QoL assessments using CLDQ/PGIS/PGIC at specified timepoints. Measurements are by standard clinical laboratory assays, ECG (QTc triplicate), MRI-PDFF/MRE imaging and validated QoL instruments as specified."}

France

Earliest CTIS Part Ii Submission Date

04-07-2025

Latest Decision Or Authorization Date

16-01-2026

Processing Time Days

196

Number Of Sites

5

Number Of Participants

33

Denmark

Earliest CTIS Part Ii Submission Date

04-07-2025

Latest Decision Or Authorization Date

16-01-2026

Processing Time Days

196

Number Of Sites

2

Number Of Participants

30

Germany

Earliest CTIS Part Ii Submission Date

30-06-2025

Latest Decision Or Authorization Date

19-01-2026

Processing Time Days

203

Number Of Sites

3

Number Of Participants

14

Poland

Earliest CTIS Part Ii Submission Date

03-07-2025

Latest Decision Or Authorization Date

20-01-2026

Processing Time Days

201

Number Of Sites

4

Number Of Participants

25

Belgium

Earliest CTIS Part Ii Submission Date

03-07-2025

Latest Decision Or Authorization Date

16-01-2026

Processing Time Days

197

Number Of Sites

2

Number Of Participants

15

Primary sponsor

Full Name

Protara Therapeutics Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Psi Cro AG

Responsibilities

sponsorDuties codes: 1,10,11,12,13,2,5,6,9 (various operational trial responsibilities as listed in submission)

Name

Premier Research Group S.L.

Responsibilities

sponsorDuties code: 8

Name

Almac Clinical Services Limited

Responsibilities

sponsorDuties code: 14

Name

4g Clinical LLC

Responsibilities

sponsorDuties code: 3

Name

Medical Research Network Limited

Responsibilities

Site Professional Support

Third parties

• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"sponsorDuties codes: 4; email: support@clario.com","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"sponsorDuties codes: 4; email: support@clario.com","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"Medical Research Network Limited","duties_or_roles":"Site Professional Support","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Pharmapace Inc.","duties_or_roles":"sponsorDuties codes: 10","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Participant reimbursement","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"eCOA and code 7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Psi Cro AG","duties_or_roles":"sponsorDuties codes: 1,10,11,12,13,2,5,6,9","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"CluePoints","duties_or_roles":"Risk Based Monitoring","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Premier Research Group S.L.","duties_or_roles":"sponsorDuties code: 8","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"sponsorDuties code: 14","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"4g Clinical LLC","duties_or_roles":"sponsorDuties code: 3","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Pharmaceutical company"}