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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Open-Label, Dose-Selection: Dose 1 | Experimental |
| |
| Open-Label, Dose-Selection: Dose 2 | Experimental |
| |
| Open-Label, Dose-Selection: Dose 3 | Experimental |
| |
| Double-Blind, Placebo-Controlled: High Dose | Experimental |
| |
| Double-Blind, Placebo-Controlled: Low Dose | Experimental |
| |
| Double-Blind, Placebo-Controlled: Placebo | Placebo Comparator |
| |
| Open Label Extension: High Dose | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Choline Chloride for Injection | Drug | Intravenous use |
|
| 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 |
| 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 |
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Key Inclusion Criteria:
Key Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Chief Scientific Operations Officer | Contact | 16468440337 | clinicaltrials@protaratx.com |
| Name | Affiliation | Role |
|---|---|---|
| Chief Scientific Operations Officer | Protara Therapeutics | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Colorado School of Medicine | Recruiting | Aurora | Colorado | 80045 | United States |
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The Open-Label Dose Selection Phase will be open label, and the Double-Blind, Placebo-Controlled Phase will be double blind. The Open Label Extension Phase will be open label.
| Open Label Extension: Low Dose | Experimental |
|
| Placebo | Drug | Intravenous use |
|
| 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 |
| 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: 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: 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: 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 |
| Floridian Clinical Research | Recruiting | Miami Lakes | Florida | 33016 | United States |
|
| Nebraska Medicine | Not yet recruiting | Omaha | Nebraska | 68105 | United States |
|
| Columbia University Medical Center/ New York Presbyterian Hospital | Not yet recruiting | New York | New York | 10032 | United States |
|
| Duke Clinic - Abdominal Transplant Research Office | Recruiting | Durham | North Carolina | 27710 | United States |
|
| Cleveland Clinic | Recruiting | Cleveland | Ohio | 44195 | United States |
|
| Pinnacle Clinical Research- San Antonio | Recruiting | San Antonio | Texas | 78229 | United States |
|
| University Hospitals Leuven, Campus Gasthuisberg | Recruiting | Leuven | 3000 | Belgium |
|
| Aalborg University Hospital, Department of Medical Gastroenterology | Recruiting | Aalborg | 9100 | Denmark |
|
| Rigshospitalet - University Hospital Copenhagen | Recruiting | Copenhagen | 2100 | Denmark |
|
| Beaujon Hospital - APHP | Recruiting | Clichy | 92110 | France |
|
| Rennes University Hospital Center - Pontchaillou Site | Not yet recruiting | Rennes | 35000 | France |
|
| CHRU Nancy - Barbois Hospital | Not yet recruiting | Vandœuvre-lès-Nancy | 54511 | France |
|
| Charite - University Hospital Berlin | Recruiting | Berlin | 13353 | Germany |
|
| University Duisburg-Essen, University Hospital Essen | Not yet recruiting | Essen | 45147 | Germany |
|
| M. Pirogow Provincial Specialized Hospital in Lodz, Nutritional Treatment Center | Recruiting | Lodz | 90-532 | Poland |
|
| Czerniakowski Hospital Sp. z o.o. (LCC) | Recruiting | Warsaw | 00-739 | Poland |
|
| ID | Term |
|---|---|
| D002796 | Choline Deficiency |
| D000090124 | Intestinal Failure |
| D006963 | Hyperphagia |
| ID | Term |
|---|---|
| D014804 | Vitamin B Deficiency |
| D001361 | Avitaminosis |
| D003677 | Deficiency Diseases |
| D044342 | Malnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D007410 | Intestinal Diseases |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D012817 | Signs and Symptoms, Digestive |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D002794 | Choline |
| D007267 | Injections |
| ID | Term |
|---|---|
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D000588 | Amines |
| D050337 | Trimethyl Ammonium Compounds |
| D000644 | Quaternary Ammonium Compounds |
| D009861 | Onium Compounds |
| D004333 | Drug Administration Routes |
| D004358 | Drug Therapy |
| D013812 | Therapeutics |
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