Efficacy and Safety of TD-1473 in Crohn's Disease | NCT03635112

ID	Type	Description	Link
2018-001272-37	EudraCT Number

Status Module

Description Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Active Treatment TD-1473 with Dose A	Active Comparator	1 oral Dose A daily of TD-1473 for 12 weeks in subjects with moderately to-severely active CD. Subjects who complete Induction will continue to receive TD-1473 at Dose A in the Active Treatment Arm for up to 48 additional weeks.	Drug: TD-1473
Active Treatment TD-1473 with Dose B	Active Comparator	1 oral Dose B daily of TD-1473 for 12 weeks in subjects with moderately to-severely active CD. Subjects who complete Induction will continue to receive TD-1473 at Dose B in the Active Treatment Arm for up to 48 additional weeks.	Drug: TD-1473
Placebo	Placebo Comparator	1 oral dose daily of placebo for 12 weeks in subjects with moderately to-severely active CD. Subjects who complete Induction will receive TD-1473 at Dose A in the Active Treatment Arm for up to 48 additional weeks.	Drug: Placebo Drug: TD-1473

Name	Type	Description	Arm Group Labels	Other Names
Placebo	Drug	Placebo will be taken daily by mouth (orally) for up to 12 weeks in the morning before eating.	Placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in Crohn's Disease Activity Index (CDAI) Score	The CDAI score was generated using regression coefficients for eight different predictors of disease activity: severity of abdominal pain, general well-being, very soft/liquid stool frequency, extra-intestinal symptoms, need for antidiarrheal drugs, presence of an abdominal mass, body weight and hematocrit. Participants reported information regarding symptoms using a diary. The subscores of abdominal pain (0-3), general well-being (0-4), and number of very soft or liquid stools were then summed over the 7 days prior to each visit. Additionally, the remaining predictors were also noted and weighted to create the total CDAI score which ranged from 0-600 with a higher score indicating a worse outcome. Benchmarks for disease activity as measured by the CDAI were: <150, clinical remission; 150 to 219, mildly active disease; 220-450, moderately active disease; and >450, very severe disease.	Baseline to Week 12

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants Who Demonstrated a Clinical Response as Measured by CDAI	The CDAI score was generated using regression coefficients for eight different predictors of disease activity: severity of abdominal pain, general well-being, very soft/liquid stool frequency, extra-intestinal symptoms, need for antidiarrheal drugs, presence of an abdominal mass, body weight and hematocrit. Participants reported information regarding symptoms using a diary. The subscores of abdominal pain (0-3), general well-being (0-4), and number of very soft or liquid stools were then summed over the 7 days prior to each visit. Additionally, the remaining predictors were also noted and weighted to create the total CDAI score which ranged from 0-600 with a higher score indicating a worse outcome. Benchmarks for disease activity as measured by the CDAI were: <150, clinical remission; 150 to 219, mildly active disease; 220-450, moderately active disease; and >450, very severe disease. Clinical response was defined as a reduction from baseline of ≥100 points or CDAI <150

Eligibility Module

Name	Affiliation	Role
Medical Monitor	Theravance Biopharma	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Theravance Biopharma Investigational Site		Birmingham	Alabama	35233-2110	United States
Theravance Biopharma Investigational Site

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Participants were randomized to receive once-daily oral administrations of placebo for 12 weeks during the Induction Period. Participants who completed the Induction Period received once-daily oral administrations of TD-1473 80 mg in the Active Treatment Extension period for up to 48 additional weeks.
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jun 9, 2020	Dec 30, 2022

Arm/Group Information

ID	Title	Description
BG000	Placebo	Participants were randomized to receive once-daily oral administrations of placebo for 12 weeks during the Induction Period. Participants who completed the Induction Period received once-daily oral administrations of TD-1473 80 mg in the Active Treatment Extension period for up to 48 additional weeks.
BG001	TD-1473 80 mg	Participants were randomized to receive once-daily oral administrations of TD-1473 80 mg for 12 weeks during the Induction Period. Participants who completed the Induction Period received once-daily oral administrations of TD-1473 80 mg in the Active Treatment Extension period for up to 48 additional weeks.
BG002	TD-1473 200 mg	Participants were randomized to receive once-daily oral administrations of TD-1473 200 mg for 12 weeks during the Induction Period. Participants who completed the Induction Period received once-daily oral administrations of TD-1473 200 mg in the Active Treatment Extension period for up to 48 additional weeks.
BG003	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00039.5± 14.85 BG00137.1± 12.45 BG00240.0± 13.64 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00018 BG00128 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Hispanic or Latino

Title	Measurements
	BG0002 BG0011 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in Crohn's Disease Activity Index (CDAI) Score

The CDAI score was generated using regression coefficients for eight different predictors of disease activity: severity of abdominal pain, general well-being, very soft/liquid stool frequency, extra-intestinal symptoms, need for antidiarrheal drugs, presence of an abdominal mass, body weight and hematocrit. Participants reported information regarding symptoms using a diary. The subscores of abdominal pain (0-3), general well-being (0-4), and number of very soft or liquid stools were then summed over the 7 days prior to each visit. Additionally, the remaining predictors were also noted and weighted to create the total CDAI score which ranged from 0-600 with a higher score indicating a worse outcome.

Benchmarks for disease activity as measured by the CDAI were: <150, clinical remission; 150 to 219, mildly active disease; 220-450, moderately active disease; and >450, very severe disease.

Modified Intent-to-Treat Analysis Set: Comprised all randomized evaluable participants who received at least 1 dose of study drug, had at least one postbaseline CDAI score and had non-missing values at both baseline and postbaseline visit.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline to Week 12

ID	Title	Description
OG000	Placebo	Participants were randomized to receive once-daily oral administrations of placebo for 12 weeks during the Induction Period. Participants who completed the Induction Period received once-daily oral administrations of TD-1473 80 mg in the Active Treatment Extension period for up to 48 additional weeks.
OG001	TD-1473 80 mg	Participants were randomized to receive once-daily oral administrations of TD-1473 80 mg for 12 weeks during the Induction Period. Participants who completed the Induction Period received once-daily oral administrations of TD-1473 80 mg in the Active Treatment Extension period for up to 48 additional weeks.
OG002	TD-1473 200 mg	Participants were randomized to receive once-daily oral administrations of TD-1473 200 mg for 12 weeks during the Induction Period. Participants who completed the Induction Period received once-daily oral administrations of TD-1473 200 mg in the Active Treatment Extension period for up to 48 additional weeks.

Units	Counts
Participants	OG00033 OG00147 OG00250

Title

Denominators

Categories

Title	Measurements
	OG000-104.86± 15.496 OG001-105.62± 12.713 OG002-117.99± 12.423

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Mixed Model Repeated Measures Analysis		0.970		Least Square Mean Difference	-0.76			2-Sided	95	-40.62	39.11					Superiority
OG000 OG002		Mixed Model Repeated Measures Analysis		0.510

Secondary

Number of Participants Who Demonstrated a Clinical Response as Measured by CDAI

Benchmarks for disease activity as measured by the CDAI were: <150, clinical remission; 150 to 219, mildly active disease; 220-450, moderately active disease; and >450, very severe disease.

Clinical response was defined as a reduction from baseline of ≥100 points or CDAI <150

Modified Intent-to-Treat Analysis Set: Comprised all randomized evaluable participants who received at least 1 dose of study drug and had at least one postbaseline CDAI score.

Posted

Count of Participants

Participants

Week 12

ID	Title	Description
OG000	Placebo	Participants were randomized to receive once-daily oral administrations of placebo for 12 weeks during the Induction Period. Participants who completed the Induction Period received once-daily oral administrations of TD-1473 80 mg in the Active Treatment Extension period for up to 48 additional weeks.

Secondary

Number of Participants Who Demonstrated CDAI Clinical Remission

Benchmarks for disease activity as measured by the CDAI were: <150, clinical remission; 150 to 219, mildly active disease; 220-450, moderately active disease; and >450, very severe disease.

CDAI clinical remission was defined as a CDAI score less than 150 at Week 12.

Modified Intent-to-Treat Analysis Set: Comprised all randomized evaluable participants who received at least 1 dose of study drug and had at least one postbaseline CDAI score.

Posted

Count of Participants

Participants

Week 12

ID	Title	Description
OG000	Placebo	Participants were randomized to receive once-daily oral administrations of placebo for 12 weeks during the Induction Period. Participants who completed the Induction Period received once-daily oral administrations of TD-1473 80 mg in the Active Treatment Extension period for up to 48 additional weeks.

Secondary

Change From Baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD) at Week 12

The SES-CD incorporated 4 descriptors: the ulcer size, the proportion of surface covered by ulcer, the proportion of surface covered by other lesions, and the presence of stenosis. Each descriptor was scored in 5 segments (ileum, right colon, transverse colon, left colon, and rectum). The total score ranged from 0 to 56, with higher scores indicating a worse outcome.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline to Week 12

ID	Title	Description
OG000	Placebo	Participants were randomized to receive once-daily oral administrations of placebo for 12 weeks during the Induction Period. Participants who completed the Induction Period received once-daily oral administrations of TD-1473 80 mg in the Active Treatment Extension period for up to 48 additional weeks.
OG001	TD-1473 80 mg	Participants were randomized to receive once-daily oral administrations of TD-1473 80 mg for 12 weeks during the Induction Period. Participants who completed the Induction Period received once-daily oral administrations of TD-1473 80 mg in the Active Treatment Extension period for up to 48 additional weeks.

Secondary

Number of Participants With Endoscopic Response at Week 12

Endoscopic Response was defined as a reduction of SES-CD score or Endoscopic Remission (defined as SES-CD ≤ 2) at Week 12.

Modified Intent-to-Treat Analysis Set: Comprised all randomized evaluable participants who received at least 1 dose of study drug and had at least one postbaseline CDAI score.

Posted

Count of Participants

Participants

Week 12

ID	Title	Description
OG000	Placebo	Participants were randomized to receive once-daily oral administrations of placebo for 12 weeks during the Induction Period. Participants who completed the Induction Period received once-daily oral administrations of TD-1473 80 mg in the Active Treatment Extension period for up to 48 additional weeks.
OG001	TD-1473 80 mg	Participants were randomized to receive once-daily oral administrations of TD-1473 80 mg for 12 weeks during the Induction Period. Participants who completed the Induction Period received once-daily oral administrations of TD-1473 80 mg in the Active Treatment Extension period for up to 48 additional weeks.
OG002	TD-1473 200 mg	Participants were randomized to receive once-daily oral administrations of TD-1473 200 mg for 12 weeks during the Induction Period. Participants who completed the Induction Period received once-daily oral administrations of TD-1473 200 mg in the Active Treatment Extension period for up to 48 additional weeks.

Secondary

Number of Participants With Stool Frequency and Abdominal Pain (SFAP) Clinical Remission

SFAP clinical remission was defined as an abdominal pain score ≤1 (on a scale of 0-3 with 0 representing 'no pain' and 3 representing 'severe pain'), stool frequency ≤2.8, and both not worse than baseline at Week 12.

Modified Intent-to-Treat Analysis Set: Comprised all randomized evaluable participants who received at least 1 dose of study drug and had at least one postbaseline CDAI score.

Posted

Count of Participants

Participants

Week 12

ID	Title	Description
OG000	Placebo	Participants were randomized to receive once-daily oral administrations of placebo for 12 weeks during the Induction Period. Participants who completed the Induction Period received once-daily oral administrations of TD-1473 80 mg in the Active Treatment Extension period for up to 48 additional weeks.
OG001	TD-1473 80 mg	Participants were randomized to receive once-daily oral administrations of TD-1473 80 mg for 12 weeks during the Induction Period. Participants who completed the Induction Period received once-daily oral administrations of TD-1473 80 mg in the Active Treatment Extension period for up to 48 additional weeks.
OG002	TD-1473 200 mg

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Participants were randomized to receive once-daily oral administrations of placebo for 12 weeks during the Induction Period. Participants who completed the Induction Period received once-daily oral administrations of TD-1473 80 mg in the Active Treatment Extension period for up to 48 additional weeks.	1	38	3	38	11	38
EG001	TD-1473 80 mg	Participants were randomized to receive once-daily oral administrations of TD-1473 80 mg for 12 weeks during the Induction Period. Participants who completed the Induction Period received once-daily oral administrations of TD-1473 80 mg in the Active Treatment Extension period for up to 48 additional weeks.	0	58	9	58	23	58
EG002	TD-1473 80mg Post-Placebo	Participants who were treated with placebo in Induction Period and switched to TD-1473 80mg in Active Treatment Extension period.	0	33	3	33	7	33
EG003	TD-1473 200 mg	Participants were randomized to receive once-daily oral administrations of TD-1473 200 mg for 12 weeks during the Induction Period. Participants who completed the Induction Period received once-daily oral administrations of TD-1473 200 mg in the Active Treatment Extension period for up to 48 additional weeks.	0	63	10	63	22	63

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Crohn's Disease	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected38 at risk EG0016 affected58 at risk EG0021 affected33 at risk EG0038 affected63 at risk
Intestinal perforation	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected38 at risk EG0011 affected58 at risk EG0020 affected33 at risk EG003
Intussusception	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected38 at risk EG0010 affected58 at risk EG0021 affected33 at risk EG003
Pancreatitis acute	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0001 affected38 at risk EG0010 affected58 at risk EG0020 affected33 at risk EG003
COVID-19 pneumonia	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0001 affected38 at risk EG0010 affected58 at risk EG0020 affected33 at risk EG003
Rectal abscess	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 affected38 at risk EG0010 affected58 at risk EG0020 affected33 at risk EG003
Granuloma	General disorders	MedDRA 24.1	Systematic Assessment	EG0001 affected38 at risk EG0010 affected58 at risk EG0020 affected33 at risk EG003
Drug hypersensitivity	Immune system disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected38 at risk EG0010 affected58 at risk EG0021 affected33 at risk EG003
Intentional overdose	Injury, poisoning and procedural complications	MedDRA 24.1	Systematic Assessment	EG0000 affected38 at risk EG0010 affected58 at risk EG0020 affected33 at risk EG003
Transaminases increased	Investigations	MedDRA 24.1	Systematic Assessment	EG0001 affected38 at risk EG0010 affected58 at risk EG0020 affected33 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected38 at risk EG0011 affected58 at risk EG0020 affected33 at risk EG003
Depression	Psychiatric disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected38 at risk EG0011 affected58 at risk EG0020 affected33 at risk EG003
Vasculitis	Vascular disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected38 at risk EG0011 affected58 at risk EG0020 affected33 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0001 affected38 at risk EG0011 affected58 at risk EG0021 affected33 at risk EG0034 affected63 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected38 at risk EG0014 affected58 at risk EG0020 affected33 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 24.1	Systematic Assessment	EG0002 affected38 at risk EG0011 affected58 at risk EG0021 affected33 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected38 at risk EG0013 affected58 at risk EG0020 affected33 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 24.1	Systematic Assessment	EG0002 affected38 at risk EG0011 affected58 at risk EG0020 affected33 at risk EG003
Crohn's disease	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0003 affected38 at risk EG0018 affected58 at risk EG0022 affected33 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected38 at risk EG0013 affected58 at risk EG0020 affected33 at risk EG003
Headache	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0003 affected38 at risk EG0013 affected58 at risk EG0021 affected33 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 affected38 at risk EG0010 affected58 at risk EG0021 affected33 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0001 affected38 at risk EG0011 affected58 at risk EG0022 affected33 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 24.1	Systematic Assessment	EG0002 affected38 at risk EG0014 affected58 at risk EG0020 affected33 at risk EG003
SARS-CoV-2 test positive	Investigations	MedDRA 24.1	Systematic Assessment	EG0000 affected38 at risk EG0011 affected58 at risk EG0020 affected33 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0001 affected38 at risk EG0014 affected58 at risk EG0020 affected33 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0001 affected38 at risk EG0011 affected58 at risk EG0022 affected33 at risk EG003

ID	Term
D003424	Crohn Disease
D015212	Inflammatory Bowel Diseases

ID	Term
D005759	Gastroenteritis
D005767	Gastrointestinal Diseases
D004066	Digestive System Diseases
D007410	Intestinal Diseases