Trial Outcomes & Findings for Efficacy and Safety of Combination Grazoprevir (MK-5172)/Elbasvir (MK-8742) Versus Sofosbuvir + Pegylated Interferon + Ribavirin in Hepatitis C Virus Genotype 1, 4 or 6 Infection (MK-5172-077) (NCT NCT02358044)

Last Updated: 2018-10-03

Results Overview

Hepatitis C Virus ribonucleic acid (HCV-RNA) levels in plasma were measured using the Roche COBAS®AmpliPrep/COBAS® TaqMan® HCV Test, v2.0 on blood samples drawn from each participant. SVR12 was defined as HCV RNA below the lower limit of quantification (\<LLOQ) at 12 weeks after the end of all study therapy. The primary efficacy hypothesis for this study was that the percentage of participants achieving SVR12 in the grazoprevir plus elbasvir arm was non-inferior to the percentage in the SOF plus PR arm. A secondary statistical analysis was performed to determine whether the percentage of participants achieving SVR12 in the grazoprevir plus elbasvir arm was superior to the percentage in the SOF plus PR arm.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

257 participants

Primary outcome timeframe

12 weeks after end of all therapy (Study Week 24)

Results posted on

2018-10-03

Participant Flow

A total of 257 participants were randomized to treatment: 129 to Grazoprevir + Elbasvir arm and 128 to Sofosbuvir plus Pegylated Interferon/Ribavirin (SOF + PR) arm. Two participants in the SOF + PR arm withdrew from study prior to treatment.

Participant milestones

Participant milestones
Measure	Grazoprevir + Elbasvir Participants receive a fixed-dose combination (FDC) tablet of 100 mg grazoprevir and 50 mg elbasvir for 12 weeks, followed by 24 weeks of follow-up.	SOF + PR Participants receive SOF (400 mg) combined with PegIntron (1.5 mcg/kg) plus RBV (1000-1200 mg weight-based dose) for 12 weeks, followed by 24 weeks of follow-up.
Overall Study STARTED	129	128
Overall Study Treated	129	126
Overall Study COMPLETED	127	121
Overall Study NOT COMPLETED	2	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Grazoprevir + Elbasvir Participants receive a fixed-dose combination (FDC) tablet of 100 mg grazoprevir and 50 mg elbasvir for 12 weeks, followed by 24 weeks of follow-up.	SOF + PR Participants receive SOF (400 mg) combined with PegIntron (1.5 mcg/kg) plus RBV (1000-1200 mg weight-based dose) for 12 weeks, followed by 24 weeks of follow-up.
Overall Study Adverse Event	0	1
Overall Study Lost to Follow-up	2	1
Overall Study Physician Decision	0	1
Overall Study Withdrawal by Subject	0	4

Baseline Characteristics

Efficacy and Safety of Combination Grazoprevir (MK-5172)/Elbasvir (MK-8742) Versus Sofosbuvir + Pegylated Interferon + Ribavirin in Hepatitis C Virus Genotype 1, 4 or 6 Infection (MK-5172-077)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Grazoprevir + Elbasvir n=129 Participants Participants receive a fixed-dose combination (FDC) tablet of 100 mg grazoprevir and 50 mg elbasvir for 12 weeks, followed by 24 weeks of follow-up.	SOF + PR n=126 Participants Participants receive SOF (400 mg) combined with PegIntron (1.5 mcg/kg) plus RBV (1000-1200 mg weight-based dose) for 12 weeks, followed by 24 weeks of follow-up.	Total n=255 Participants Total of all reporting groups
Age, Continuous	47.6 years STANDARD_DEVIATION 12.4 • n=5 Participants	48.2 years STANDARD_DEVIATION 12.4 • n=7 Participants	47.9 years STANDARD_DEVIATION 12.4 • n=5 Participants
Sex: Female, Male Female	74 Participants n=5 Participants	64 Participants n=7 Participants	138 Participants n=5 Participants
Sex: Female, Male Male	55 Participants n=5 Participants	62 Participants n=7 Participants	117 Participants n=5 Participants

PRIMARY outcome

Timeframe: 12 weeks after end of all therapy (Study Week 24)

Population: FAS; all randomized participants who receive at least one dose of study treatment. Two participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.

Outcome measures

Outcome measures
Measure	Grazoprevir + Elbasvir n=129 Participants Participants receive a fixed-dose combination (FDC) tablet of 100 mg grazoprevir and 50 mg elbasvir for 12 weeks, followed by 24 weeks of follow-up.	SOF + PR n=126 Participants Participants receive SOF (400 mg) combined with PegIntron (1.5 mcg/kg) plus RBV (1000-1200 mg weight-based dose) for 12 weeks, followed by 24 weeks of follow-up.
Primary: Percentage of Participants Achieving Sustained Virologic Response at 12 Weeks After the End of All Treatment (SVR12)	99.2 percentage of participants	90.5 percentage of participants

PRIMARY outcome

Timeframe: Treatment + First 14 days of follow-up (Up to Week 14)

Population: All Subjects as Treated (ASaT) population; all randomized participants who received at least one dose of study treatment. Two participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.

An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that was temporally associated with the use of the Sponsor's product, was also an AE. The percentage of participants who experienced at least one AE was reported for each treatment arm.

Outcome measures

Outcome measures
Measure	Grazoprevir + Elbasvir n=129 Participants Participants receive a fixed-dose combination (FDC) tablet of 100 mg grazoprevir and 50 mg elbasvir for 12 weeks, followed by 24 weeks of follow-up.	SOF + PR n=126 Participants Participants receive SOF (400 mg) combined with PegIntron (1.5 mcg/kg) plus RBV (1000-1200 mg weight-based dose) for 12 weeks, followed by 24 weeks of follow-up.
Percentage of Participants Experiencing at Least One Adverse Event (AE) During the Treatment Period Plus First 14 Follow-up Days	51.9 percentage of participants	93.7 percentage of participants

PRIMARY outcome

Timeframe: Up to Week 12

Population: ASaT population; all randomized participants who received at least one dose of study treatment. Two participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.

An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that was temporally associated with the use of the Sponsor's product, was also an AE. The percentage of participants who discontinued study treatment due to an AE was reported for each treatment arm. Participants that discontinued study drug treatment due to an AE may have still continued on trial.

Outcome measures

Outcome measures
Measure	Grazoprevir + Elbasvir n=129 Participants Participants receive a fixed-dose combination (FDC) tablet of 100 mg grazoprevir and 50 mg elbasvir for 12 weeks, followed by 24 weeks of follow-up.	SOF + PR n=126 Participants Participants receive SOF (400 mg) combined with PegIntron (1.5 mcg/kg) plus RBV (1000-1200 mg weight-based dose) for 12 weeks, followed by 24 weeks of follow-up.
Percentage of Participants Discontinuing Study Treatment Due to an AE	0.8 percentage of participants	0.8 percentage of participants

SECONDARY outcome

Timeframe: Treatment + First 14 days of follow-up (Up to Week 14)

Tier 1 safety events were pre-specified by the protocol to evaluate safety and test the safety superiority hypothesis. Tier 1 safety events were chosen to assess broad tolerability, hematological side effects and liver-related laboratory abnormalities. For this study, Tier 1 safety events included: any serious drug-related AE, any drug-related AE leading to permanent discontinuation (DC) of all study drugs, neutrophil count \<0.75 x 10\^9/L, hemoglobin \<10 g/dL, severe depression, hepatic events of clinical interest (defined by abnormal increases in alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], or alkaline phosphatase \[ALP\]), or events meeting stopping rule criteria for DC from trial (due to abnormal increases of ALT, AST, or ALP with/without pre-specified related AEs). The percentage of participants who experienced each individual event that was defined as a Tier 1 safety event during the study treatment period was reported for each treatment arm.

Outcome measures

Outcome measures
Measure	Grazoprevir + Elbasvir n=129 Participants Participants receive a fixed-dose combination (FDC) tablet of 100 mg grazoprevir and 50 mg elbasvir for 12 weeks, followed by 24 weeks of follow-up.	SOF + PR n=126 Participants Participants receive SOF (400 mg) combined with PegIntron (1.5 mcg/kg) plus RBV (1000-1200 mg weight-based dose) for 12 weeks, followed by 24 weeks of follow-up.
Percentage of Participants Experiencing at Least One Tier 1 Safety Event (Key Safety Parameter) During the Treatment Period and First 14 Follow-up Days Total Tier 1 AEs	0.8 percentage of participants	27.8 percentage of participants
Percentage of Participants Experiencing at Least One Tier 1 Safety Event (Key Safety Parameter) During the Treatment Period and First 14 Follow-up Days Tier 1 AE: Serious drug-related AE	0.0 percentage of participants	2.4 percentage of participants
Percentage of Participants Experiencing at Least One Tier 1 Safety Event (Key Safety Parameter) During the Treatment Period and First 14 Follow-up Days Tier 1 AE: DC due to drug-related AE	0.0 percentage of participants	0.8 percentage of participants
Percentage of Participants Experiencing at Least One Tier 1 Safety Event (Key Safety Parameter) During the Treatment Period and First 14 Follow-up Days Tier 1 AE: Neutrophil count <0.75 x 10^9/L	0.0 percentage of participants	12.7 percentage of participants
Percentage of Participants Experiencing at Least One Tier 1 Safety Event (Key Safety Parameter) During the Treatment Period and First 14 Follow-up Days Tier 1 AE: Hemoglobin <10 g/dL	0.8 percentage of participants	14.3 percentage of participants
Percentage of Participants Experiencing at Least One Tier 1 Safety Event (Key Safety Parameter) During the Treatment Period and First 14 Follow-up Days Tier 1 AE: Severe depression	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants Experiencing at Least One Tier 1 Safety Event (Key Safety Parameter) During the Treatment Period and First 14 Follow-up Days Tier 1 AE: Hepatic event of clinical interest	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants Experiencing at Least One Tier 1 Safety Event (Key Safety Parameter) During the Treatment Period and First 14 Follow-up Days Tier 1 AE: Trial DC due to stopping rule	0.0 percentage of participants	0.0 percentage of participants

SECONDARY outcome

Timeframe: 24 weeks after end of all therapy (Study Week 36)

HCV-RNA levels in plasma were measured using the Roche COBAS®AmpliPrep/COBAS® TaqMan® HCV Test, v2.0 on blood samples drawn from each participant. SVR24 was defined as HCV RNA \<LLOQ at 24 weeks after the end of all study therapy.

Outcome measures

Outcome measures
Measure	Grazoprevir + Elbasvir n=129 Participants Participants receive a fixed-dose combination (FDC) tablet of 100 mg grazoprevir and 50 mg elbasvir for 12 weeks, followed by 24 weeks of follow-up.	SOF + PR n=126 Participants Participants receive SOF (400 mg) combined with PegIntron (1.5 mcg/kg) plus RBV (1000-1200 mg weight-based dose) for 12 weeks, followed by 24 weeks of follow-up.
Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Ending Study Treatment (SVR24)	98.4 percentage of participants	89.7 percentage of participants

SECONDARY outcome

Timeframe: 4 weeks after end of all therapy (Study Week 16)

HCV-RNA levels in plasma were measured using the Roche COBAS®AmpliPrep/COBAS® TaqMan® HCV Test, v2.0 on blood samples drawn from each participant. SVR4 was defined as HCV RNA \<LLOQ at 4 weeks after the end of all study therapy.

Outcome measures

Outcome measures
Measure	Grazoprevir + Elbasvir n=129 Participants Participants receive a fixed-dose combination (FDC) tablet of 100 mg grazoprevir and 50 mg elbasvir for 12 weeks, followed by 24 weeks of follow-up.	SOF + PR n=126 Participants Participants receive SOF (400 mg) combined with PegIntron (1.5 mcg/kg) plus RBV (1000-1200 mg weight-based dose) for 12 weeks, followed by 24 weeks of follow-up.
Percentage of Participants Achieving Sustained Virologic Response 4 Weeks After Ending Study Treatment (SVR4)	99.2 percentage of participants Interval 95.8 to 100.0	92.1 percentage of participants Interval 85.9 to 96.1

Adverse Events

Grazoprevir + Elbasvir

Serious events: 1 serious events

Other events: 44 other events

Deaths: 0 deaths

SOF + PR

Serious events: 6 serious events

Other events: 114 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Grazoprevir + Elbasvir n=129 participants at risk Participants receive a fixed-dose combination (FDC) tablet of 100 mg grazoprevir and 50 mg elbasvir for 12 weeks, followed by 24 weeks of follow-up.	SOF + PR n=126 participants at risk Participants receive SOF (400 mg) combined with PegIntron (1.5 mcg/kg) plus RBV (1000-1200 mg weight-based dose) for 12 weeks, followed by 24 weeks of follow-up.
Blood and lymphatic system disorders Anaemia	0.00% 0/129 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.	0.79% 1/126 • Number of events 1 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.
Cardiac disorders Angina pectoris	0.00% 0/129 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.	0.79% 1/126 • Number of events 1 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.
Gastrointestinal disorders Proctitis	0.00% 0/129 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.	0.79% 1/126 • Number of events 1 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.
Infections and infestations Infection	0.00% 0/129 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.	0.79% 1/126 • Number of events 1 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.
Infections and infestations Influenza	0.00% 0/129 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.	0.79% 1/126 • Number of events 1 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.
Infections and infestations Proctitis infectious	0.00% 0/129 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.	0.79% 1/126 • Number of events 1 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.
Infections and infestations Tooth abscess	0.78% 1/129 • Number of events 1 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.	0.00% 0/126 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/129 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.	0.79% 1/126 • Number of events 1 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.
Nervous system disorders Cerebrovascular accident	0.00% 0/129 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.	0.79% 1/126 • Number of events 1 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.
Psychiatric disorders Drug dependence	0.00% 0/129 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.	0.79% 1/126 • Number of events 1 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
Publication restrictions are in place

Restriction type: OTHER

Measure	Grazoprevir + Elbasvir n=129 participants at risk Participants receive a fixed-dose combination (FDC) tablet of 100 mg grazoprevir and 50 mg elbasvir for 12 weeks, followed by 24 weeks of follow-up.	SOF + PR n=126 participants at risk Participants receive SOF (400 mg) combined with PegIntron (1.5 mcg/kg) plus RBV (1000-1200 mg weight-based dose) for 12 weeks, followed by 24 weeks of follow-up.
Blood and lymphatic system disorders Anaemia	0.78% 1/129 • Number of events 1 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.	11.9% 15/126 • Number of events 15 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.
Blood and lymphatic system disorders Neutropenia	0.00% 0/129 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.	8.7% 11/126 • Number of events 15 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.
Gastrointestinal disorders Dyspepsia	0.78% 1/129 • Number of events 1 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.	6.3% 8/126 • Number of events 10 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.
Gastrointestinal disorders Nausea	6.2% 8/129 • Number of events 9 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.	10.3% 13/126 • Number of events 23 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.
General disorders Asthenia	6.2% 8/129 • Number of events 10 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.	23.8% 30/126 • Number of events 36 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.
General disorders Chills	1.6% 2/129 • Number of events 4 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.	16.7% 21/126 • Number of events 27 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.
General disorders Fatigue	7.0% 9/129 • Number of events 9 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.	25.4% 32/126 • Number of events 48 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.
General disorders Influenza like illness	0.78% 1/129 • Number of events 1 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.	18.3% 23/126 • Number of events 40 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.
General disorders Pyrexia	1.6% 2/129 • Number of events 2 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.	54.0% 68/126 • Number of events 191 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.
Injury, poisoning and procedural complications Accidental overdose	0.00% 0/129 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.	6.3% 8/126 • Number of events 12 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.
Metabolism and nutrition disorders Decreased appetite	0.78% 1/129 • Number of events 1 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.	12.7% 16/126 • Number of events 16 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.
Musculoskeletal and connective tissue disorders Arthralgia	3.9% 5/129 • Number of events 5 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.	11.1% 14/126 • Number of events 25 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.
Musculoskeletal and connective tissue disorders Back pain	2.3% 3/129 • Number of events 4 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.	6.3% 8/126 • Number of events 8 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.
Musculoskeletal and connective tissue disorders Myalgia	3.1% 4/129 • Number of events 6 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.	15.1% 19/126 • Number of events 47 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.
Nervous system disorders Dizziness	3.1% 4/129 • Number of events 5 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.	5.6% 7/126 • Number of events 10 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.
Nervous system disorders Headache	13.2% 17/129 • Number of events 31 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.	39.7% 50/126 • Number of events 97 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.
Psychiatric disorders Irritability	0.00% 0/129 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.	7.9% 10/126 • Number of events 11 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/129 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.	10.3% 13/126 • Number of events 27 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.3% 3/129 • Number of events 3 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.	7.9% 10/126 • Number of events 10 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.
Skin and subcutaneous tissue disorders Alopecia	0.78% 1/129 • Number of events 1 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.	14.3% 18/126 • Number of events 18 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.
Skin and subcutaneous tissue disorders Pruritus	1.6% 2/129 • Number of events 2 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.	6.3% 8/126 • Number of events 9 • Up to Follow-up Week 24 ASaT population; all randomized participants who received at least one dose of study treatment. Two randomized participants in the SOF + PR arm withdrew from study prior to treatment and were excluded from analysis.