Trial Outcomes & Findings for The Effectiveness of ABT-450/r - Ombitasvir, ± Dasabuvir, ± Ribavirin in Patients With Chronic Hepatitis C -An Observational Study in Ireland (NCT NCT02582671)

Last Updated: 2019-05-06

Results Overview

SVR12 was defined as hepatitis C virus ribonucleic acid (HCV RNA) level less than 50 IU/mL 12 weeks after the last actual dose of study drug. The core population (CP) consisted of participants who met all inclusion criteria and were adequately treated according to the standard of care and within local label recommendations for their specific disease characteristics (cirrhotic status, genotype). The core population with sufficient follow-up data 12 weeks after the last actual dose of study drug (CPSFU12) was defined as all CP participants who fulfilled one of the following criteria: * evaluable HCV RNA data ≥70 days after the last actual dose of the ABBVIE REGIMEN * an HCV RNA value ≥50 IU/mL at the last measurement post-baseline * HCV RNA \<50 IU/mL at the last measurement post-baseline, but no HCV RNA measurement ≥70 days after the last actual dose of the ABBVIE REGIMEN due to reasons related to safety (e.g. dropped out due to AE) or virologic failure

Recruitment status

COMPLETED

Target enrollment

101 participants

Primary outcome timeframe

12 weeks after the last actual dose of study drug

Results posted on

2019-05-06

Participant Flow

Safety population: all enrolled participants who received at least one dose of the ABBVIE REGIMEN. The prescribed ABBVIE REGIMEN needed to be known.

Participant milestones

Participant milestones
Measure	Participants With HCV Genotype 1 Ombitasvir/paritaprevir/ritonavir (two 12.5 mg/75 mg/50 mg co-formulated tablets once daily); ± dasabuvir (tablet; 250 mg twice daily); ± weight-based ribavirin (tablet; 1000 or 1200 mg divided twice a day) up to 24 weeks
Overall Study STARTED	101
Overall Study COMPLETED	99
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Participants With HCV Genotype 1 Ombitasvir/paritaprevir/ritonavir (two 12.5 mg/75 mg/50 mg co-formulated tablets once daily); ± dasabuvir (tablet; 250 mg twice daily); ± weight-based ribavirin (tablet; 1000 or 1200 mg divided twice a day) up to 24 weeks
Overall Study Failure to return	1
Overall Study Other, not specified	1

Baseline Characteristics

The Effectiveness of ABT-450/r - Ombitasvir, ± Dasabuvir, ± Ribavirin in Patients With Chronic Hepatitis C -An Observational Study in Ireland

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Participants With HCV Genotype 1 n=101 Participants Ombitasvir/paritaprevir/ritonavir (two 12.5 mg/75 mg/50 mg co-formulated tablets once daily); ± dasabuvir (tablet; 250 mg twice daily); ± weight-based ribavirin (tablet; 1000 or 1200 mg divided twice a day) up to 24 weeks
Age, Continuous	54 years STANDARD_DEVIATION 13.8 • n=93 Participants
Sex: Female, Male Female	67 Participants n=93 Participants
Sex: Female, Male Male	34 Participants n=93 Participants
Race/Ethnicity, Customized Race or Ethnicity · Black or African American	1 Participants n=93 Participants
Race/Ethnicity, Customized Race or Ethnicity · Hispanic/Latino	1 Participants n=93 Participants
Race/Ethnicity, Customized Race or Ethnicity · Non-Hispanic White	99 Participants n=93 Participants
Hepatitis C genotype Genotype 1a	31 Participants n=93 Participants
Hepatitis C genotype Genotype 1b	70 Participants n=93 Participants

PRIMARY outcome

Timeframe: 12 weeks after the last actual dose of study drug

Population: Core population (CP) and core population with sufficient follow-up data 12 weeks after the last actual dose of study drug (CPSFU12) are defined in the outcome measure description

Outcome measures

Outcome measures
Measure	Participants With HCV Genotype 1 n=101 Participants Ombitasvir/paritaprevir/ritonavir (two 12.5 mg/75 mg/50 mg co-formulated tablets once daily); ± dasabuvir (tablet; 250 mg twice daily); ± weight-based ribavirin (tablet; 1000 or 1200 mg divided twice a day) up to 24 weeks
Percentage of Participants Achieving Sustained Virologic Response 12 Weeks Post-treatment (SVR12) Core population (CP)	97.0 percentage of participants Interval 91.6 to 99.0
Percentage of Participants Achieving Sustained Virologic Response 12 Weeks Post-treatment (SVR12) CPSFU12	98.0 percentage of participants Interval 93.0 to 99.4

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: Core population: Participants meeting all inclusion criteria and who were adequately treated according to the standard of care and within local label recommendations for their specific disease characteristics (cirrhotic status, genotype)

Virologic response was defined as hepatitis C virus ribonucleic acid (HCV RNA) level less than 50 IU/mL at the end of treatment.

Outcome measures

Outcome measures
Measure	Participants With HCV Genotype 1 n=101 Participants Ombitasvir/paritaprevir/ritonavir (two 12.5 mg/75 mg/50 mg co-formulated tablets once daily); ± dasabuvir (tablet; 250 mg twice daily); ± weight-based ribavirin (tablet; 1000 or 1200 mg divided twice a day) up to 24 weeks
Percentage of Participants With Virologic Response at End of Treatment (EOT)	97.0 Percentage of participants Interval 91.6 to 99.0

SECONDARY outcome

Timeframe: From the end of treatment through the end of study (maximum of 48 weeks post-treatment)

Relapse was defined as hepatitis C virus ribonucleic acid (HCV RNA) level less than 50 IU/mL at the end of treatment followed by HCV RNA level greater than or equal to 50 IU/mL.

Outcome measures

Outcome measures
Measure	Participants With HCV Genotype 1 n=96 Participants Ombitasvir/paritaprevir/ritonavir (two 12.5 mg/75 mg/50 mg co-formulated tablets once daily); ± dasabuvir (tablet; 250 mg twice daily); ± weight-based ribavirin (tablet; 1000 or 1200 mg divided twice a day) up to 24 weeks
Percentage of Participants With Relapse	0 percentage of participants Interval 0.0 to 3.8

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: Core population (those meeting inclusion criteria and treated according to the standard of care and w/in local label guidelines for specific disease characteristics \[cirrhotic status, genotype\]) who had at least 1 undetectable or unquantifiable, on-treatment HCV RNA measurement and at least 1 on-treatment or end of treatment measurement thereafter

Viral breakthrough was defined as at least 1 documented hepatitis C virus ribonucleic acid (HCV RNA) level less than 50 IU/mL followed by HCV RNA level greater than or equal to 50 IU/mL during treatment.

Outcome measures

Outcome measures
Measure	Participants With HCV Genotype 1 n=101 Participants Ombitasvir/paritaprevir/ritonavir (two 12.5 mg/75 mg/50 mg co-formulated tablets once daily); ± dasabuvir (tablet; 250 mg twice daily); ± weight-based ribavirin (tablet; 1000 or 1200 mg divided twice a day) up to 24 weeks
Percentage of Participants With Viral Breakthrough	0 percentage of participants Interval 0.0 to 5.5

SECONDARY outcome

Timeframe: Up to 24 weeks

On-treatment virologic failure was defined as breakthrough (at least 1 documented hepatitis C virus ribonucleic acid (HCV RNA) less than 50 IU/mL followed by HCV RNA greater than or equal to 50 IU/mL during treatment) or failure to suppress (each measured on-treatment HCV RNA value greater than or equal to 50 IU/mL).

Outcome measures

Outcome measures
Measure	Participants With HCV Genotype 1 n=101 Participants Ombitasvir/paritaprevir/ritonavir (two 12.5 mg/75 mg/50 mg co-formulated tablets once daily); ± dasabuvir (tablet; 250 mg twice daily); ± weight-based ribavirin (tablet; 1000 or 1200 mg divided twice a day) up to 24 weeks
Percentage of Participants With On-treatment Virologic Failure	0 percentage of participants

SECONDARY outcome

Timeframe: Up to 12 weeks after the last actual dose of study drug

Relapse was defined as hepatitis C virus ribonucleic acid (HCV RNA) less than 50 IU/mL at end of treatment or at the last on treatment HCV RNA measurement followed by HCV RNA greater than or equal to 50 IU/mL post-treatment.

Outcome measures

Outcome measures
Measure	Participants With HCV Genotype 1 n=96 Participants Ombitasvir/paritaprevir/ritonavir (two 12.5 mg/75 mg/50 mg co-formulated tablets once daily); ± dasabuvir (tablet; 250 mg twice daily); ± weight-based ribavirin (tablet; 1000 or 1200 mg divided twice a day) up to 24 weeks
Percentage of Participants Meeting Relapse Criteria	0 percentage of participants

SECONDARY outcome

Timeframe: Up to 24 weeks

Premature study drug discontinuation was defined as participants who prematurely discontinued study drug with no on-treatment virologic failure.

Outcome measures

Outcome measures
Measure	Participants With HCV Genotype 1 n=101 Participants Ombitasvir/paritaprevir/ritonavir (two 12.5 mg/75 mg/50 mg co-formulated tablets once daily); ± dasabuvir (tablet; 250 mg twice daily); ± weight-based ribavirin (tablet; 1000 or 1200 mg divided twice a day) up to 24 weeks
Percentage of Participants Meeting Premature Study Drug Discontinuation Criteria	2.0 percentage of participants

SECONDARY outcome

Timeframe: 12 weeks after the last actual dose of study drug

The number of participants with missing SVR12 data or SVR12 nonresponder participants who did not meet criteria for on-treatment virologic failure, relapse, premature treatment discontinuation, and who did not have an Insufficient virological response reported was documented.

Outcome measures

Outcome measures
Measure	Participants With HCV Genotype 1 n=101 Participants Ombitasvir/paritaprevir/ritonavir (two 12.5 mg/75 mg/50 mg co-formulated tablets once daily); ± dasabuvir (tablet; 250 mg twice daily); ± weight-based ribavirin (tablet; 1000 or 1200 mg divided twice a day) up to 24 weeks
Percentage of Participants With Missing Sustained Virologic Response 12 Weeks Post-Treatment (SVR12) Data and/or Nonresponders Who Did Not Meet Specific SVR12 Nonresponder Criteria	1.0 percentage of participants

Adverse Events

Participants Who Did Not Receive Ribavirin

Serious events: 1 serious events

Other events: 47 other events

Deaths: 0 deaths

Participants Who Received Ribavirin

Serious events: 0 serious events

Other events: 27 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Participants Who Did Not Receive Ribavirin n=66 participants at risk Ombitasvir/paritaprevir/ritonavir (two 12.5 mg/75 mg/50 mg co-formulated tablets once daily); ± dasabuvir (tablet; 250 mg twice daily)	Participants Who Received Ribavirin n=35 participants at risk Ombitasvir/paritaprevir/ritonavir (two 12.5 mg/75 mg/50 mg co-formulated tablets once daily); ± dasabuvir (tablet; 250 mg twice daily); + weight-based ribavirin (tablet; 1000 or 1200 mg divided twice a day) up to 24 weeks
Eye disorders MACULAR DEGENERATION	1.5% 1/66 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 28 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	0.00% 0/35 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 28 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.

Other adverse events

Additional Information

Global Medical Services

AbbVie

Phone: 800-633-9110

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.
Publication restrictions are in place

Restriction type: OTHER

Measure	Participants Who Did Not Receive Ribavirin n=66 participants at risk Ombitasvir/paritaprevir/ritonavir (two 12.5 mg/75 mg/50 mg co-formulated tablets once daily); ± dasabuvir (tablet; 250 mg twice daily)	Participants Who Received Ribavirin n=35 participants at risk Ombitasvir/paritaprevir/ritonavir (two 12.5 mg/75 mg/50 mg co-formulated tablets once daily); ± dasabuvir (tablet; 250 mg twice daily); + weight-based ribavirin (tablet; 1000 or 1200 mg divided twice a day) up to 24 weeks
Blood and lymphatic system disorders ANAEMIA	0.00% 0/66 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 28 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	14.3% 5/35 • Number of events 5 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 28 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.
Gastrointestinal disorders CONSTIPATION	3.0% 2/66 • Number of events 2 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 28 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	8.6% 3/35 • Number of events 3 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 28 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.
Gastrointestinal disorders DIARRHOEA	12.1% 8/66 • Number of events 8 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 28 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	11.4% 4/35 • Number of events 4 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 28 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.
Gastrointestinal disorders DYSPEPSIA	1.5% 1/66 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 28 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	8.6% 3/35 • Number of events 3 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 28 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.
Gastrointestinal disorders NAUSEA	21.2% 14/66 • Number of events 14 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 28 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	8.6% 3/35 • Number of events 3 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 28 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.
General disorders FATIGUE	40.9% 27/66 • Number of events 27 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 28 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	37.1% 13/35 • Number of events 13 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 28 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.
Infections and infestations LOWER RESPIRATORY TRACT INFECTION	7.6% 5/66 • Number of events 5 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 28 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	11.4% 4/35 • Number of events 4 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 28 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.
Infections and infestations RESPIRATORY TRACT INFECTION	0.00% 0/66 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 28 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	5.7% 2/35 • Number of events 2 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 28 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.
Metabolism and nutrition disorders DECREASED APPETITE	1.5% 1/66 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 28 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	5.7% 2/35 • Number of events 2 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 28 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.
Nervous system disorders HEADACHE	25.8% 17/66 • Number of events 17 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 28 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	11.4% 4/35 • Number of events 4 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 28 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.
Psychiatric disorders DEPRESSED MOOD	4.5% 3/66 • Number of events 3 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 28 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	8.6% 3/35 • Number of events 3 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 28 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.
Psychiatric disorders INSOMNIA	4.5% 3/66 • Number of events 3 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 28 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	11.4% 4/35 • Number of events 4 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 28 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.
Psychiatric disorders SLEEP DISORDER	6.1% 4/66 • Number of events 4 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 28 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	5.7% 2/35 • Number of events 2 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 28 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.
Respiratory, thoracic and mediastinal disorders COUGH	7.6% 5/66 • Number of events 5 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 28 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	0.00% 0/35 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 28 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.
Respiratory, thoracic and mediastinal disorders DYSPNOEA	3.0% 2/66 • Number of events 2 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 28 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	5.7% 2/35 • Number of events 2 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 28 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.
Respiratory, thoracic and mediastinal disorders EPISTAXIS	0.00% 0/66 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 28 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	5.7% 2/35 • Number of events 2 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 28 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.
Skin and subcutaneous tissue disorders DRY SKIN	1.5% 1/66 • Number of events 1 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 28 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	14.3% 5/35 • Number of events 5 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 28 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.
Skin and subcutaneous tissue disorders PRURITUS	7.6% 5/66 • Number of events 5 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 28 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	8.6% 3/35 • Number of events 3 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 28 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.
Skin and subcutaneous tissue disorders RASH	7.6% 5/66 • Number of events 5 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 28 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.	5.7% 2/35 • Number of events 2 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 28 weeks). TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.