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

Phase 3RecruitingNCT06910943

Protara Therapeutics129 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

129

Conditions

Choline Deficiency Liver Injury

Interventions

Choline Chloride for InjectionDRUG

Intravenous use

PlaceboDRUG

Intravenous use

Eligibility

Sex: ALLMin age: 12 Years

Medical Language ↔ Plain English

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

Locations (14)

University of Colorado School of Medicine

Aurora, Colorado, United States

RECRUITING

Columbia University Medical Center/ New York Presbyterian Hospital

New York, New York, United States

NOT_YET_RECRUITING

Duke Clinic - Abdominal Transplant Research Office

Durham, North Carolina, United States

RECRUITING

Cleveland Clinic

Cleveland, Ohio, United States

RECRUITING

University Hospitals Leuven, Campus Gasthuisberg

Leuven, Belgium

NOT_YET_RECRUITING

Aalborg University Hospital, Department of Medical Gastroenterology

Aalborg, Denmark

NOT_YET_RECRUITING

Rigshospitalet - University Hospital Copenhagen

Copenhagen, Denmark

RECRUITING

Beaujon Hospital - APHP

Clichy, France

NOT_YET_RECRUITING

Rennes University Hospital Center - Pontchaillou Site

Rennes, France

NOT_YET_RECRUITING

CHRU Nancy - Barbois Hospital

Vandœuvre-lès-Nancy, France

NOT_YET_RECRUITING

...and 4 more locations

Outcomes

Primary Outcomes

Open-Label Dose-Selection Phase: PK of plasma free choline (Cmax) during Week 1 and Week 8 Visits

Cmax = maximum concentration

Time frame: 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

Time frame: 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

Time frame: Week 1 to Week 8

Open-Label Dose-Selection Phase: Change from Baseline in plasma free choline concentrations at Week 8

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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)

Time frame: 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

Time frame: 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

Time frame: Week 8 to Week 64

Secondary Outcomes

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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Central Contacts

Chief Scientific Operations Officer

CONTACT

16468440337 clinicaltrials@protaratx.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Time frame: Week 1 to Week 8

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

Time frame: Week 1 to Week 24

Double-Blind, Placebo-Controlled Phase: Percentage of participants achieving plasma free choline concentration Cmax ≥ 9.5 nmol/mL at Week 8

Cmax = maximum concentration

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Week 64