Trial Outcomes & Findings for A Randomized, Double-blind Study to Assess the Safety and Efficacy of EDP-305 in Subjects With Liver-biopsy Proven NASH (NCT NCT04378010)

Results Overview

Proportion of participants who achieve ≥1 stage improvement in fibrosis without worsening of steatohepatitis and/or resolution of steatohepatitis and no worsening of liver fibrosis as determined by liver biopsy.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

98 participants

Primary outcome timeframe

Week 72

Results posted on

2023-05-19

Participant Flow

Male and female subjects with liver biopsy proven NASH between the ages of 18 and 75 years, inclusive, and with a NAS of 4 or greater with a score of at least 1 in each component of the NAS (steatosis scored 0-3, lobular inflammation scored 0-3, ballooning scored 0-2) and fibrosis stage 2 or 3 using the NASH Clinical Research Network (CRN) Histologic Scoring System were eligible for inclusion. Subjects had to be negative for hepatitis B, hepatitis C, and human immunodeficiency virus (HIV).

Screening assessments were conducted within 70 days prior to the first dose of study drug (i.e., Study Days -70 to -1). Screening assessments were performed and confirmed sequentially as follows: a) medical history and other noninvasive assessments, b) laboratory assessments, c) MRI-PDFF and MRE and, lastly, d) liver biopsy.

Participant milestones

Participant milestones
Measure	EDP-305 1.5 mg Once a day orally for 72 weeks EDP-305 1.5 mg: Tablet	EDP-305 2 mg Once a day orally for 72 weeks EDP-305 2 mg: Tablet	Placebo Once a day orally for 72 weeks Placebo: Tablet
Overall Study STARTED	32	34	32
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	32	34	32

Reasons for withdrawal

Reasons for withdrawal
Measure	EDP-305 1.5 mg Once a day orally for 72 weeks EDP-305 1.5 mg: Tablet	EDP-305 2 mg Once a day orally for 72 weeks EDP-305 2 mg: Tablet	Placebo Once a day orally for 72 weeks Placebo: Tablet
Overall Study Adverse Event	8	14	4
Overall Study Withdrawal by Subject	0	2	1
Overall Study Protocol Violation	2	1	4
Overall Study Study terminated by Sponsor	22	16	22
Overall Study Subject inability to complete study visit	0	0	1
Overall Study Subject never dosed	0	1	0

Baseline Characteristics

A Randomized, Double-blind Study to Assess the Safety and Efficacy of EDP-305 in Subjects With Liver-biopsy Proven NASH

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	EDP-305 1.5 mg n=32 Participants Once a day orally for 72 weeks EDP-305 1.5 mg: Tablet	EDP-305 2 mg n=33 Participants Once a day orally for 72 weeks EDP-305 2 mg: Tablet	Placebo n=32 Participants Once a day orally for 72 weeks Placebo: Tablet	Total n=97 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	22 Participants n=5 Participants	27 Participants n=7 Participants	27 Participants n=5 Participants	76 Participants n=4 Participants
Age, Categorical >=65 years	10 Participants n=5 Participants	6 Participants n=7 Participants	5 Participants n=5 Participants	21 Participants n=4 Participants
Age, Continuous	55.7 Years STANDARD_DEVIATION 12.67 • n=5 Participants	56.2 Years STANDARD_DEVIATION 8.14 • n=7 Participants	52.7 Years STANDARD_DEVIATION 11.33 • n=5 Participants	56.0 Years STANDARD_DEVIATION 10.53 • n=4 Participants
Sex: Female, Male Female	20 Participants n=5 Participants	19 Participants n=7 Participants	19 Participants n=5 Participants	58 Participants n=4 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	14 Participants n=7 Participants	13 Participants n=5 Participants	39 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants
Race (NIH/OMB) White	29 Participants n=5 Participants	27 Participants n=7 Participants	28 Participants n=5 Participants	84 Participants n=4 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment Argentina	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Region of Enrollment Canada	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Region of Enrollment United States	30 Participants n=5 Participants	31 Participants n=7 Participants	31 Participants n=5 Participants	92 Participants n=4 Participants
Region of Enrollment United Kingdom	0 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants

PRIMARY outcome

Timeframe: Week 72

Population: Due to study termination, the biopsy at Week 72 was not performed for any participant. Hence, there were no results to report.

Proportion of participants who achieve ≥1 stage improvement in fibrosis without worsening of steatohepatitis and/or resolution of steatohepatitis and no worsening of liver fibrosis as determined by liver biopsy.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: ITT population: Intent-to-treat population (ITT) defined as all participants who randomized to treatment. Participants were analyzed according to the treatment to which they were randomized. The overall numbers of participants by group were N = 32, N = 33, and N = 32. The numbers of participants with available data for the specified time frame were n = 7, n = 6 and n = 7 for EDP-305 1.5, 2mg and Placebo groups, respectively, presented as LS Mean (95% CI).

5D-itch scale, change from baseline at Week 12. Change from baseline for 5D-itch scale was analyzed using a restricted maximum likelihood-based mixed model repeated measures (MMRM) technique. The model included treatment, visit, treatment-by-visit interaction as fixed effects along with baseline NAS score and baseline score for 5D-itch scale as covariate. A multidimensional 5D-itch scale developed by Elman (Elman et al., 2010) indicated sum of 0-2 = score of 1, sum of 3-5 = score of 2, sum of 6-10 = score of 3, sum of 11-13 = score of 4, and sum of 14-16 = score of 5. The total 5D score was obtained by summing up the five domain scores and ranges between 5 (no pruritus) and 25 (most severe pruritus).

Outcome measures

Outcome measures
Measure	EDP-305 1.5 mg n=7 Participants Once a day orally for 72 weeks EDP-305 1.5 mg: Tablet	EDP-305 2 mg n=6 Participants Once a day orally for 72 weeks EDP-305 2 mg: Tablet	Placebo n=7 Participants Once a day orally for 72 weeks Placebo: Tablet
Change in 5D-itch Scale From Baseline	2.275 score on a scale Interval -1.227 to 5.777	4.594 score on a scale Interval 0.676 to 8.513	2.714 score on a scale Interval -0.955 to 6.384

SECONDARY outcome

Timeframe: Week 72

Population: Due to study termination, the biopsy at Week 72 was not performed for any participants. Hence, there were no results to report.

Description of endpoint is Proportion of participants with improvement of fibrosis by at least 1 stage and/or resolution of NASH without worsening of either as determined by liver biopsy.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 72

Population: Due to study termination, the biopsy at Week 72 was not performed for any participant. Hence, there were no results to report.

Proportion of participants with no worsening of fibrosis combined with no worsening of NASH as determined by liver biopsy.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 72

Population: Due to study termination, the biopsy at Week 72 was not performed for any participant. Hence, there were no results to report.

Proportion of participants with resolution of fibrosis as determined by liver biopsy at Week 72.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 72

Population: Due to study termination, the biopsy at Week 72 was not performed for any participant. Hence, there were no results to report.

Proportion of participants with improvement in each histologic feature of NASH by at least 1 point as determined by liver biopsy at Week 72.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 72

Population: Due to study termination, the biopsy at Week 72 was not performed for any participant. Hence, there were no results to report.

Proportion of participants with improvement of fibrosis by ≥ 2 stages by liver biopsy.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 72

Population: Due to study termination, the biopsy at Week 72 was not performed for any participant. Hence, there were no results to report.

Proportion of participants with improvement in NAS by at least 2 points with no worsening of fibrosis as determined by liver biopsy at Week 72.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 72

Population: Due to study termination, the biopsy at Week 72 was not performed for any participant. Hence, there were no results to report.

Proportion of participants with improvement of fibrosis and resolution of NASH as a composite endpoint as defined by both endpoints being met in the same participant at week 72.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 72

Population: Due to study termination, the biopsy at Week 72 was not performed for any participant. Hence, there were no results to report.

Proportion of participants with resolution of NASH and no worsening of liver fibrosis at Week 72.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 72

Population: Due to study termination, the biopsy at Week 72 was not performed for any participant. Hence, there were no results to report.

Proportion of participants with histological progression to cirrhosis as determined by liver biopsy at Week 72.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 1 to Week 72

Population: Safety population (SAF) defined as all participants who received at least one dose of study drug. Participants were included in the treatment group that corresponded to the study drug received during the study.

Treatment emergent adverse events (TEAEs) were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug. TEAEs were regarded as leading to discontinuation if they led to discontinuation of the study drug.

Outcome measures

Outcome measures
Measure	EDP-305 1.5 mg n=32 Participants Once a day orally for 72 weeks EDP-305 1.5 mg: Tablet	EDP-305 2 mg n=33 Participants Once a day orally for 72 weeks EDP-305 2 mg: Tablet	Placebo n=32 Participants Once a day orally for 72 weeks Placebo: Tablet
Participants With TEAEs Leading to Discontinuation	8 Participants	14 Participants	4 Participants

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Intent-to-treat (ITT) Population: The ITT participants were analyzed according to the treatment to which they were randomized. The overall numbers of participants by group were N = 32, N = 33, and N = 32. The numbers of participants with available data for the specified time frame were n = 24, n =17 and n= 26 for EDP-305 1.5, 2mg and Placebo groups respectively, presented as LS Mean (95% CI).

Percentage change of fat in the liver as assessed by magnetic resonance imaging proton density fat fraction (MRI PDFF) from Baseline to Week 12.

Outcome measures

Outcome measures
Measure	EDP-305 1.5 mg n=24 Participants Once a day orally for 72 weeks EDP-305 1.5 mg: Tablet	EDP-305 2 mg n=17 Participants Once a day orally for 72 weeks EDP-305 2 mg: Tablet	Placebo n=26 Participants Once a day orally for 72 weeks Placebo: Tablet
Percentage Change of Fat in the Liver From Baseline	-25.612 Percentage change Interval -39.387 to -11.837	-26.069 Percentage change Interval -40.19 to -11.948	-14.351 Percentage change Interval -26.908 to -1.794

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Intent-to-treat (ITT) Population: ITT participants were those randomized to treatment. The ITT participants were analyzed according to the treatment to which they were randomized. The overall numbers of participants by group were N = 32, N = 33, and N = 32. The numbers of participants with available data for the specified time frame were n = 24, n = 17 and n = 26 for EDP-305 1.5, 2mg groups and Placebo, respectively, presented as LS Mean (95% CI).

Change in liver stiffness by magnetic resonance elastography (MRE) in kilopascal (kPa) from Baseline at Week 12.

Outcome measures

Outcome measures
Measure	EDP-305 1.5 mg n=24 Participants Once a day orally for 72 weeks EDP-305 1.5 mg: Tablet	EDP-305 2 mg n=17 Participants Once a day orally for 72 weeks EDP-305 2 mg: Tablet	Placebo n=26 Participants Once a day orally for 72 weeks Placebo: Tablet
Change in Liver Stiffness From Baseline	0.163 Kilopascal (kPa) Interval -0.469 to 0.794	0.623 Kilopascal (kPa) Interval -0.04 to 1.285	-0.428 Kilopascal (kPa) Interval -1.013 to 0.157

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Intent-to-treat (ITT) Population: ITT participants were those randomized to treatment. The ITT participants were analyzed according to the treatment to which they were randomized. The overall numbers of participants by group were N = 32, N = 33, and N = 32. The numbers of participants with available data for the specified time frame were n = 28, n = 26 and n=30 for EDP-305 1.5, 2mg groups and Placebo respectively.

Change in Triglycerides from Baseline at Week 12.

Outcome measures

Outcome measures
Measure	EDP-305 1.5 mg n=28 Participants Once a day orally for 72 weeks EDP-305 1.5 mg: Tablet	EDP-305 2 mg n=26 Participants Once a day orally for 72 weeks EDP-305 2 mg: Tablet	Placebo n=30 Participants Once a day orally for 72 weeks Placebo: Tablet
Change in Triglycerides From Baseline	-0.16 Millimoles per liter (mmol/L) Standard Deviation 0.725	-0.14 Millimoles per liter (mmol/L) Standard Deviation 0.839	-0.06 Millimoles per liter (mmol/L) Standard Deviation 0.752

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Safety population: Safety population (SAF) defined as all participants who received at least one dose of study drug. Participants were included in the treatment group that corresponded to the study drug received during the study. The overall numbers of participants by group were N = 32, N = 33, and N = 32. The numbers of participants with available data for the specified time frame were n = 27, n = 24, and n = 27 for EDP-305 1.5 mg and 2 mg groups and Placebo respectively.

Change in adiponectin from Baseline at Week 12.

Outcome measures

Outcome measures
Measure	EDP-305 1.5 mg n=27 Participants Once a day orally for 72 weeks EDP-305 1.5 mg: Tablet	EDP-305 2 mg n=24 Participants Once a day orally for 72 weeks EDP-305 2 mg: Tablet	Placebo n=27 Participants Once a day orally for 72 weeks Placebo: Tablet
Change in Adiponectin From Baseline	330.25 Micrograms per liter (µg/L) Standard Deviation 1309.414	-85.44 Micrograms per liter (µg/L) Standard Deviation 1199.182	228.27 Micrograms per liter (µg/L) Standard Deviation 866.829

SECONDARY outcome

Timeframe: 2-4 hours post dose at Week 12

Population: Pharmacokinetic (PK) Population: All participants receiving active study drug and having any measurable plasma concentration of study drug at any timepoint. The overall numbers of participants by group were N = 32, N = 33, and N = 32. The numbers of participants with available data for the specified time frame were n = 6 and n = 7 for EDP-305 1.5 and 2mg groups respectively.

Plasma concentration at second post dose (2-4 hours post dose) at Week 12.

Outcome measures

Outcome measures
Measure	EDP-305 1.5 mg n=6 Participants Once a day orally for 72 weeks EDP-305 1.5 mg: Tablet	EDP-305 2 mg n=7 Participants Once a day orally for 72 weeks EDP-305 2 mg: Tablet	Placebo Once a day orally for 72 weeks Placebo: Tablet
Plasma Concentration of EDP-305	17.3783 Nanograms per milliliter (ng/mL) Standard Deviation 15.13460	30.0286 Nanograms per milliliter (ng/mL) Standard Deviation 24.07237	—

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Intent-to-treat (ITT) Population: ITT participants were those randomized to treatment. The ITT participants were analyzed according to the treatment to which they were randomized. The overall numbers of participants by group were N = 32, N = 33, and N = 32. The numbers of participants with available data for the specified time frame were n = 28, n = 25 and n= 30 for EDP-305 1.5, 2mg groups and Placebo, respectively, presented as LS Mean (95% CI).

Change in VAS from Baseline at Week 12. Change from baseline was analyzed using a restricted maximum likelihood-based MMRM technique. Two separate scales were used to assess pruritus. An itch VAS was used to record the intensity of the pruritus by Furue (Furue et al., 2013). Scale referred to no pruritus (0 point) and the end of the scale to the most severe pruritus (10 points). If the VAS score was greater than zero (i.e. itch), a multidimensional 5D-itch scale developed by Elman (Elman et al., 2010) indicated sum of 0-2 = score of 1, sum of 3-5 = score of 2, sum of 6-10 = score of 3, sum of 11-13 = score of 4, and sum of 14-16 = score of 5. It was used to assess five different dimensions of pruritus within the last two weeks. The five dimensions assessed were duration, degree, direction, disability, and distribution. The total 5D itch score was obtained by summing up the five domain scores and ranges between 5 (no pruritus) and 25 (most severe pruritus).

Outcome measures

Outcome measures
Measure	EDP-305 1.5 mg n=28 Participants Once a day orally for 72 weeks EDP-305 1.5 mg: Tablet	EDP-305 2 mg n=25 Participants Once a day orally for 72 weeks EDP-305 2 mg: Tablet	Placebo n=30 Participants Once a day orally for 72 weeks Placebo: Tablet
Change in VAS (Visual Analog Score) From Baseline	12.773 score on a scale Interval 1.386 to 24.161	18.548 score on a scale Interval 7.661 to 29.435	5.563 score on a scale Interval -5.274 to 16.399

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Intent-to-treat (ITT) Population: ITT participants were those randomized to treatment. The ITT participants were analyzed according to the treatment to which they were randomized. The overall numbers of participants by group were N = 32, N = 33, and N = 32. The numbers of participants with available data for the specified time frame were n = 28, n = 26, and n = 30 for EDP-305 1.5, 2 mg groups and Placebo respectively.

Change in Total Cholesterol from Baseline to Week 12 versus placebo.

Outcome measures

Outcome measures
Measure	EDP-305 1.5 mg n=28 Participants Once a day orally for 72 weeks EDP-305 1.5 mg: Tablet	EDP-305 2 mg n=26 Participants Once a day orally for 72 weeks EDP-305 2 mg: Tablet	Placebo n=30 Participants Once a day orally for 72 weeks Placebo: Tablet
Change in Total Cholesterol From Baseline	0.07 mmol/L Standard Deviation 0.977	-0.07 mmol/L Standard Deviation 1.116	0.00 mmol/L Standard Deviation 0.946

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Intent-to-treat (ITT) Population: ITT participants were those randomized to treatment. The ITT participants were analyzed according to the treatment to which they were randomized. The overall numbers of participants by group were N = 32, N = 33, and N = 32. The numbers of participants with available data for the specified time frame were n = 27, n = 25, and n = 30 for EDP-305 1.5, 2 mg groups and Placebo respectively.

Change in HDL from Baseline at week 12.

Outcome measures

Outcome measures
Measure	EDP-305 1.5 mg n=27 Participants Once a day orally for 72 weeks EDP-305 1.5 mg: Tablet	EDP-305 2 mg n=25 Participants Once a day orally for 72 weeks EDP-305 2 mg: Tablet	Placebo n=30 Participants Once a day orally for 72 weeks Placebo: Tablet
Change in HDL From Baseline	-0.08 mmol/L Standard Deviation 0.200	-0.11 mmol/L Standard Deviation 0.255	0.01 mmol/L Standard Deviation 0.149

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Intent-to-treat (ITT) Population: ITT participants were those randomized to treatment. The ITT participants were analyzed according to the treatment to which they were randomized. The overall numbers of participants by group were N = 32, N = 33, and N = 32. The numbers of participants with available data for the specified time frame were n = 28, n = 26, and n = 30 for EDP-305 1.5 mg, 2mg groups and Placebo respectively.

Change in LDL From Baseline to Week 12.

Outcome measures

Outcome measures
Measure	EDP-305 1.5 mg n=28 Participants Once a day orally for 72 weeks EDP-305 1.5 mg: Tablet	EDP-305 2 mg n=26 Participants Once a day orally for 72 weeks EDP-305 2 mg: Tablet	Placebo n=30 Participants Once a day orally for 72 weeks Placebo: Tablet
Change in LDL From Baseline	0.24 mmol/L Standard Deviation 0.856	0.08 mmol/L Standard Deviation 0.949	-0.03 mmol/L Standard Deviation 0.835

Adverse Events

EDP-305 1.5 mg

Serious events: 2 serious events

Other events: 28 other events

Deaths: 0 deaths

EDP-305 2 mg

Serious events: 0 serious events

Other events: 31 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	EDP-305 1.5 mg n=32 participants at risk Once a day orally for 72 weeks EDP-305 1.5 mg: Tablet	EDP-305 2 mg n=33 participants at risk Once a day orally for 72 weeks EDP-305 2 mg: Tablet	Placebo n=32 participants at risk Once a day orally for 72 weeks Placebo: Tablet
Gastrointestinal disorders Abdominal pain	3.1% 1/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	0.00% 0/33 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	0.00% 0/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.
Gastrointestinal disorders Pancreatitis	3.1% 1/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	0.00% 0/33 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	0.00% 0/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.

Other adverse events

Additional Information

Alaa Ahmad

Enanta Pharmaceuticals, Inc

Phone: 1-617-607-0800

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Measure	EDP-305 1.5 mg n=32 participants at risk Once a day orally for 72 weeks EDP-305 1.5 mg: Tablet	EDP-305 2 mg n=33 participants at risk Once a day orally for 72 weeks EDP-305 2 mg: Tablet	Placebo n=32 participants at risk Once a day orally for 72 weeks Placebo: Tablet
Skin and subcutaneous tissue disorders Pruritus	78.1% 25/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	75.8% 25/33 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	37.5% 12/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.
Skin and subcutaneous tissue disorders Rash	9.4% 3/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	6.1% 2/33 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	3.1% 1/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	6.1% 2/33 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	0.00% 0/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.
Investigations Blood creatine phosphokinase increased	6.2% 2/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	3.0% 1/33 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	0.00% 0/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.
Investigations Lipase increased	0.00% 0/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	6.1% 2/33 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	6.2% 2/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.
Gastrointestinal disorders Abdominal pain upper	6.2% 2/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	12.1% 4/33 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	3.1% 1/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.
Gastrointestinal disorders Nausea	6.2% 2/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	3.0% 1/33 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	9.4% 3/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.
Gastrointestinal disorders Toothache	0.00% 0/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	0.00% 0/33 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	6.2% 2/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.
Nervous system disorders Headache	6.2% 2/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	9.1% 3/33 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	6.2% 2/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.
Nervous system disorders Dizziness	6.2% 2/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	9.1% 3/33 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	3.1% 1/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.
General disorders Fatigue	6.2% 2/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	9.1% 3/33 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	0.00% 0/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	3.0% 1/33 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	6.2% 2/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.
Gastrointestinal disorders Diarrhoea	3.1% 1/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	6.1% 2/33 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	9.4% 3/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.
Gastrointestinal disorders Abdominal pain	9.4% 3/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	3.0% 1/33 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	3.1% 1/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.
Gastrointestinal disorders Vomiting	3.1% 1/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	3.0% 1/33 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	6.2% 2/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.
Gastrointestinal disorders Abdominal pain lower	6.2% 2/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	3.0% 1/33 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	0.00% 0/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.
Infections and infestations Urinary tract infection	12.5% 4/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	9.1% 3/33 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	12.5% 4/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.
Infections and infestations COVID-19	9.4% 3/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	3.0% 1/33 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	3.1% 1/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.
Investigations Blood pressure increased	0.00% 0/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	0.00% 0/33 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	6.2% 2/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.
Injury, poisoning and procedural complications Foot fracture	0.00% 0/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	0.00% 0/33 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	6.2% 2/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.
Injury, poisoning and procedural complications Post vaccination syndrome	0.00% 0/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	0.00% 0/33 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	6.2% 2/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.
Vascular disorders Hypertension	3.1% 1/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	6.1% 2/33 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	3.1% 1/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	3.1% 1/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	0.00% 0/33 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	6.2% 2/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	0.00% 0/33 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.	6.2% 2/32 • Day 1 to Week 72 Treatment emergent adverse events were defined as AEs occurring or worsening on or after the first dose of study drug until the last dose of study drug.