Dose-Selection, Safety and Efficacy Study with Open-Label Extension of Choline Chloride for Injection in Adolescent and Adult Patients with Intestinal Failure Receiving Long-Term Parenteral Support

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Protara Therapeutics Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18], Diseases [C] - Digestive System Diseases [C06]

Trial duration

25 Sep 2025 → ongoing

Decision date (initial)

2025-07-23

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Protara Therapeutics Inc.

External identifiers

EU CT number

2024-519496-26-00

ClinicalTrials.gov

NCT06910943

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety, Pharmacokinetic

Dose-Selection (DS)
1. Description of PK parameters following treatment with Choline Chloride for Injection by rich PK sampling
2. To assess the safety of Choline Chloride for Injection

Double-Blind (DB)
1. To demonstrate Choline Chloride for Injection as a source of choline at Week 8
2. Safety: To assess the safety of Choline Chloride for Injection versus Placebo

Open-Label (OL)
1. To describe plasma free choline concentrations following treatment with Choline Chloride for Injection
2. Safety: To assess the safety of Choline Chloride for Injection

Secondary objectives 17

1. Dose-Selection (DS) 1. To assess the change in liver enzymes, CPK, and homocysteine after treatment with Choline Chloride for Injection
2. Dose-Selection (DS) 2. To describe QTc changes following treatment with Choline Chloride for Injection
3. Dose-Selection (DS) 3. To describe plasma free choline concentration increases following treatment with Choline Chloride for Injection
4. Dose-Selection (DS) 4. To describe maintenance of normal plasma free choline concentration increases following treatment with Choline Chloride for Injection
5. Dose-Selection (DS) 5. To assess anthropomorphic change after treatment with Choline Chloride for Injection
6. Dose Selection (DS) 6. To assess the change in hepatic steatosis after treatment with Choline Chloride for Injection
7. Double-Blind (DB) 1. To demonstrate Choline Chloride for Injection as a source of choline at Week 24
8. Double-Blind (DB) 2. To describe plasma free choline concentration increases following treatment with Choline Chloride for Injection versus Placebo
9. Double-Blind (DB) 3. To describe maintenance of normal plasma free choline concentrations increases following treatment with Choline Chloride for Injection versus Placebo
10. Double-Blind (DB) 4. To assess anthropomorphic change after treatment with Choline Chloride for Injection versus Placebo
11. Double-Blind (DB) 5. To assess the change in liver enzymes, CPK, and homocysteine after treatment with Choline Chloride for Injection versus Placebo
12. Double-Blind (DB) 6. To assess the change in hepatic steatosis and fibrosis after treatment with Choline Chloride for Injection versus Placebo
13. Double-Blind (DB) 7. To explore the effect of Choline Chloride for Injection versus Placebo on patient-reported quality of life
14. Open-Label (OL) 1. To assess the change in liver enzymes, CPK, and homocysteine after treatment with Choline Chloride for Injection
15. Open-Label (OL) 2. To assess anthropomorphic change after treatment with Choline Chloride for Injection
16. Open-Label (OL) 3. To assess the change in hepatic steatosis and fibrosis after treatment with Choline Chloride for Injection
17. Open-Label (OL) 4. To explore the effect of Choline Chloride on patient-reported quality of life during the OLE

Conditions and MedDRA coding

Intestinal Failure

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. 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.
2. 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.
3. 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
4. 4. Females of childbearing potential must have a negative urine pregnancy test at screening

Exclusion criteria 13

1. 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
2. 10. Participation in an interventional clinical study with drugs within 6 weeks prior to screening
3. 2. Evidence of systemic active infection at the time of dosing
4. 3. Participants intending to take non-study intervention choline supplements or choline-containing multivitamins during the course of the study
5. 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
6. 5. Women who are nursing, pregnant or intending to become pregnant during the study
7. 6. Active malignancy (excluding basal cell skin tumor, low or very low risk prostate cancer, cervical carcinoma in situ and local resected cervical cancer)
8. 7. Clinically significant renal disease (defined as estimated glomerular filtration rate [eGFR] ≤ 30 mL/min/1.73 m²)
9. 8. Low B12 or low serum folic acid levels that are less than the normal range
10. 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
11. 11. Planned surgery during the study period (eg. bowel resection or fistula repair)
12. 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
13. 13. Any reason which, in the opinion of the Principal Investigator (PI), would make participation in the study against the participant’s best interests

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 7

1. 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
2. Dose-Selection (DS) 2. Change from Baseline in time-matched plasma free choline concentrations at Week 8
3. Dose-Selection (DS) 3. Safety: Incidence and severity of TEAEs; Incidence of TESAEs
4. 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
5. Double-Blind (DB) 2. Safety: Incidence and severity of TEAEs; Incidence of TESAEs
6. 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
7. Open-Label (OL) 2. Safety: Incidence and severity of TEAEs; Incidence of TESAEs

Secondary endpoints 19

1. 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
2. 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
3. Dose-Selection (DS) 3. Percentage of participants achieving plasma free choline concentration Cmax ≥ 9.5 nmol/mL at Week 8
4. Dose-Selection (DS) 4. Percentage of participants maintaining plasma free choline concentration Cmax ≥ 9.5 nmol/mL at Week 8
5. Dose-Selection (DS) 5. Change from Baseline to Week 8 in height, weight, and BMI
6. 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
7. 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
8. Double-Blind (DB) 2. Percentage of participants achieving plasma free choline concentration Cmax ≥ 9.5 nmol/mL at Week 8
9. 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)
10. Double-Blind (DB) 4. Change from Baseline to Week 8 and Week 24 in height, weight, and BMI
11. 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
12. 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
13. 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
14. 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
15. 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
16. 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
17. 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;
18. 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
19. 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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Protara Therapeutics Inc.

Sponsor organisation

Protara Therapeutics Inc.

Address

345 Park Avenue South South Floor 3rd

City

New York

Postcode

10010-1707

Country

United States

Scientific contact point

Organisation

Protara Therapeutics Inc.

Contact name

R&D

Public contact point

Organisation

Protara Therapeutics Inc.

Contact name

R&D

Third parties 12

Locations

5 EU/EEA countries · 16 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 48 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications