Trial Outcomes & Findings for The Approach Open Label Study: A Study of Volanesorsen (Formerly IONIS-APOCIIIRx) in Participants With Familial Chylomicronemia Syndrome (NCT NCT02658175)

Last Updated: 2021-08-26

Results Overview

Baseline for treatment-naïve group was defined as the average of open-label Day 1 pre-dose assessment and the last measurement prior to open-label Day 1. Baseline for CS6-volanesorsen and CS16-volanesorsen arm groups was defined as the average of index study Day 1 pre-dose assessment and the last measurement prior index study Day 1. The values at the Month 3 analysis time point were defined as the average of the Week 12 (Day 78) and Week 13 (Day 85) fasting assessments. The Month 6 analysis time point was at the end of Month 6, and the values were defined as the average of the Week 25 (Day 169) and Week 26 (Day 176) fasting assessments. The values at the Month 12 analysis time point were defined as the average of the Week 50 (Day 344) and Week 52 (Day 358) fasting assessments.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

68 participants

Primary outcome timeframe

Baseline and Months 3, 6, and 12

Results posted on

2021-08-26

Participant Flow

The study was conducted at 19 study centers in Canada, France, Italy, Netherlands, South Africa, Spain, United Kingdom and the United States from 23 December 2015 to 15 January 2020.

A total of 68 participants were enrolled into this study.

Participant milestones

Participant milestones
Measure	Treatment-naïve Group Treatment naïve group included combined group of ISIS 304801-CS7 (CS7-New) study participant and participant on placebo in index studies (ISIS 304801-CS6- Placebo \[NCT02211209\] and ISIS 304801-CS16-Placebo \[NCT02300233\]), were to receive 300 milligrams (mg) of volanesorsen as a single subcutaneous (SC) injection once weekly for Weeks 1-52 of this study. Participants were allowed dose adjustment/dose reduction based on monitoring rules. Following the Week 52 visit, participants had the option of participating in an expanded access program or continuing treatment with 300 mg of volanesorsen as a single SC injection once-weekly for up to an additional 52 weeks (Weeks 53-104) and in France participants, up to an additional 104 weeks for total of 156 weeks of treatment (Weeks 105 to Week 156) of this study until an expanded access program was approved and available in their country. Participants who were not participating in an expanded access program were to enter a 13-week post-treatment evaluation period and in France, participants not continuing treatment were to enter a 26-week post-treatment follow-up period.	CS6-Volanesorsen Participants with FCS rolling over from the ISIS 304801-CS6 (NCT02211209) index study after receiving volanesorsen, were to receive 300 mg of volanesorsen as a single SC injection once weekly for Weeks 1-52 of this study. Participants were allowed dose adjustment/dose reduction based on monitoring rules. Following the Week 52 visit, participants had the option of participating in an expanded access program or continuing treatment with 300 mg of volanesorsen as a single SC injection once-weekly for up to an additional 52 weeks (Weeks 53-104) and in France participants, up to an additional 104 weeks for total of 156 weeks of treatment (Weeks 105 to Week 156) of this study until an expanded access program was approved and available in their country. Participants who were not participating in an expanded access program were to enter a 13-week post-treatment evaluation period and in France, participants not continuing treatment were to enter a 26-week post-treatment follow-up period.	CS16-Volanesorsen Participants with FCS rolling over from the ISIS 304801-CS16 (NCT02300233) index study after receiving volanesorsen, were to receive 300 mg of volanesorsen as a single SC injection once weekly for Weeks 1-52 of this study. Participants were allowed dose adjustment/dose reduction based on monitoring rules. Following the Week 52 visit, participants had the option of participating in an expanded access program or continuing treatment with 300 mg of volanesorsen as a single SC injection once-weekly for up to an additional 52 weeks (Weeks 53-104) and in France participants, up to an additional 104 weeks for total of 156 weeks of treatment (Weeks 105 to Week 156) of this study until an expanded access program was approved and available in their country. Participants who were not participating in an expanded access program were to enter a 13-week post-treatment evaluation period and in France, participants not continuing treatment were to enter a 26-week post-treatment follow-up period.
Treatment Period: Weeks 1 to 52 STARTED	51	14	3
Treatment Period: Weeks 1 to 52 COMPLETED	36	7	3
Treatment Period: Weeks 1 to 52 NOT COMPLETED	15	7	0
1st Extended Treatment: Weeks 53 to 104 STARTED	36	7	3
1st Extended Treatment: Weeks 53 to 104 COMPLETED	15	5	1
1st Extended Treatment: Weeks 53 to 104 NOT COMPLETED	21	2	2
2nd Extended Treatment: Weeks 105 to156 STARTED	1	0	1
2nd Extended Treatment: Weeks 105 to156 COMPLETED	0	0	0
2nd Extended Treatment: Weeks 105 to156 NOT COMPLETED	1	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment-naïve Group Treatment naïve group included combined group of ISIS 304801-CS7 (CS7-New) study participant and participant on placebo in index studies (ISIS 304801-CS6- Placebo \[NCT02211209\] and ISIS 304801-CS16-Placebo \[NCT02300233\]), were to receive 300 milligrams (mg) of volanesorsen as a single subcutaneous (SC) injection once weekly for Weeks 1-52 of this study. Participants were allowed dose adjustment/dose reduction based on monitoring rules. Following the Week 52 visit, participants had the option of participating in an expanded access program or continuing treatment with 300 mg of volanesorsen as a single SC injection once-weekly for up to an additional 52 weeks (Weeks 53-104) and in France participants, up to an additional 104 weeks for total of 156 weeks of treatment (Weeks 105 to Week 156) of this study until an expanded access program was approved and available in their country. Participants who were not participating in an expanded access program were to enter a 13-week post-treatment evaluation period and in France, participants not continuing treatment were to enter a 26-week post-treatment follow-up period.	CS6-Volanesorsen Participants with FCS rolling over from the ISIS 304801-CS6 (NCT02211209) index study after receiving volanesorsen, were to receive 300 mg of volanesorsen as a single SC injection once weekly for Weeks 1-52 of this study. Participants were allowed dose adjustment/dose reduction based on monitoring rules. Following the Week 52 visit, participants had the option of participating in an expanded access program or continuing treatment with 300 mg of volanesorsen as a single SC injection once-weekly for up to an additional 52 weeks (Weeks 53-104) and in France participants, up to an additional 104 weeks for total of 156 weeks of treatment (Weeks 105 to Week 156) of this study until an expanded access program was approved and available in their country. Participants who were not participating in an expanded access program were to enter a 13-week post-treatment evaluation period and in France, participants not continuing treatment were to enter a 26-week post-treatment follow-up period.	CS16-Volanesorsen Participants with FCS rolling over from the ISIS 304801-CS16 (NCT02300233) index study after receiving volanesorsen, were to receive 300 mg of volanesorsen as a single SC injection once weekly for Weeks 1-52 of this study. Participants were allowed dose adjustment/dose reduction based on monitoring rules. Following the Week 52 visit, participants had the option of participating in an expanded access program or continuing treatment with 300 mg of volanesorsen as a single SC injection once-weekly for up to an additional 52 weeks (Weeks 53-104) and in France participants, up to an additional 104 weeks for total of 156 weeks of treatment (Weeks 105 to Week 156) of this study until an expanded access program was approved and available in their country. Participants who were not participating in an expanded access program were to enter a 13-week post-treatment evaluation period and in France, participants not continuing treatment were to enter a 26-week post-treatment follow-up period.
Treatment Period: Weeks 1 to 52 Investigator Judgment	1	0	0
Treatment Period: Weeks 1 to 52 Voluntary Withdrawal	6	2	0
Treatment Period: Weeks 1 to 52 Adverse Event or Serious Adverse Event (SAE)	8	5	0
1st Extended Treatment: Weeks 53 to 104 Investigator Judgment	1	0	0
1st Extended Treatment: Weeks 53 to 104 Voluntary Withdrawal	4	0	1
1st Extended Treatment: Weeks 53 to 104 Adverse Event or SAE	7	0	0
1st Extended Treatment: Weeks 53 to 104 Other	1	0	1
1st Extended Treatment: Weeks 53 to 104 Transferred to Early Access Programs	8	2	0
2nd Extended Treatment: Weeks 105 to156 Adverse Event or SAE	0	0	1
2nd Extended Treatment: Weeks 105 to156 Transferred to Commercial Treatment	1	0	0

Baseline Characteristics

The Approach Open Label Study: A Study of Volanesorsen (Formerly IONIS-APOCIIIRx) in Participants With Familial Chylomicronemia Syndrome

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment-naïve Group n=51 Participants Treatment naïve group included combined group of ISIS 304801-CS7 (CS7-New) study participant and participant on placebo in index studies (ISIS 304801-CS6- Placebo \[NCT02211209\] and ISIS 304801-CS16-Placebo \[NCT02300233\]), were to receive 300 mg of volanesorsen as a single SC injection once weekly for Weeks 1-52 of this study. Participants were allowed dose adjustment/dose reduction based on monitoring rules. Following the Week 52 visit, participants had the option of participating in an expanded access program or continuing treatment with 300 mg of volanesorsen as a single SC injection once-weekly for up to an additional 52 weeks (Weeks 53-104) and in France participants, up to an additional 104 weeks for total of 156 weeks of treatment (Weeks 105 to Week 156) of this study until an expanded access program was approved and available in their country. Participants who were not participating in an expanded access program were to enter a 13-week post-treatment evaluation period and in France, participants not continuing treatment were to enter a 26-week post-treatment follow-up period.	CS6-Volanesorsen n=14 Participants Participants with FCS rolling over from the ISIS 304801-CS6 (NCT02211209) index study after receiving volanesorsen, were to receive 300 mg of volanesorsen as a single SC injection once weekly for Weeks 1-52 of this study. Participants were allowed dose adjustment/dose reduction based on monitoring rules. Following the Week 52 visit, participants had the option of participating in an expanded access program or continuing treatment with 300 mg of volanesorsen as a single SC injection once-weekly for up to an additional 52 weeks (Weeks 53-104) and in France participants, up to an additional 104 weeks for total of 156 weeks of treatment (Weeks 105 to Week 156) of this study until an expanded access program was approved and available in their country. Participants who were not participating in an expanded access program were to enter a 13-week post-treatment evaluation period and in France, participants not continuing treatment were to enter a 26-week post-treatment follow-up period.	CS16-Volanesorsen n=3 Participants Participants with FCS rolling over from the ISIS 304801-CS16 (NCT02300233) index study after receiving volanesorsen, were to receive 300 mg of volanesorsen as a single SC injection once weekly for Weeks 1-52 of this study. Participants were allowed dose adjustment/dose reduction based on monitoring rules. Following the Week 52 visit, participants had the option of participating in an expanded access program or continuing treatment with 300 mg of volanesorsen as a single SC injection once-weekly for up to an additional 52 weeks (Weeks 53-104) and in France participants, up to an additional 104 weeks for total of 156 weeks of treatment (Weeks 105 to Week 156) of this study until an expanded access program was approved and available in their country. Participants who were not participating in an expanded access program were to enter a 13-week post-treatment evaluation period and in France, participants not continuing treatment were to enter a 26-week post-treatment follow-up period.	Total n=68 Participants Total of all reporting groups
Age, Continuous	47 years STANDARD_DEVIATION 14 • n=5 Participants	48 years STANDARD_DEVIATION 14 • n=7 Participants	48 years STANDARD_DEVIATION 11 • n=5 Participants	47 years STANDARD_DEVIATION 13 • n=4 Participants
Sex: Female, Male Female	34 Participants n=5 Participants	7 Participants n=7 Participants	2 Participants n=5 Participants	43 Participants n=4 Participants
Sex: Female, Male Male	17 Participants n=5 Participants	7 Participants n=7 Participants	1 Participants n=5 Participants	25 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	49 Participants n=5 Participants	14 Participants n=7 Participants	3 Participants n=5 Participants	66 Participants n=4 Participants
Ethnicity (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
Race/Ethnicity, Customized Race · White	39 Participants n=5 Participants	11 Participants n=7 Participants	3 Participants n=5 Participants	53 Participants n=4 Participants
Race/Ethnicity, Customized Race · Asian	11 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	14 Participants n=4 Participants
Race/Ethnicity, Customized Race · Other Race	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Fasting Triglyceride (TG)	2341 milligrams per decilitre (mg/dL) STANDARD_DEVIATION 1193 • n=5 Participants	1523 milligrams per decilitre (mg/dL) STANDARD_DEVIATION 946 • n=7 Participants	2081 milligrams per decilitre (mg/dL) STANDARD_DEVIATION 706 • n=5 Participants	2161 milligrams per decilitre (mg/dL) STANDARD_DEVIATION 1166 • n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Months 3, 6, and 12

Population: FAS included all participants who were enrolled and received at least one dose of study drug and who had an open-label study baseline TG assessment. Here, "number analyzed" signifies participants evaluable for this outcome measure at specified time points.

Outcome measures

Outcome measures
Measure	Treatment-naïve Group n=51 Participants Treatment naïve group included combined group of ISIS 304801-CS7 (CS7-New) study participant and participant on placebo in index studies (ISIS 304801-CS6- Placebo \[NCT02211209\] and ISIS 304801-CS16-Placebo \[NCT02300233\]), were to receive 300 mg of volanesorsen as a single SC injection once weekly for Weeks 1-52 of this study. Participants were allowed dose adjustment/dose reduction based on monitoring rules. Following the Week 52 visit, participants had the option of participating in an expanded access program or continuing treatment with 300 mg of volanesorsen as a single SC injection once-weekly for up to an additional 52 weeks (Weeks 53-104) and in France participants, up to an additional 104 weeks for total of 156 weeks of treatment (Weeks 105 to Week 156) of this study until an expanded access program was approved and available in their country. Participants who were not participating in an expanded access program were to enter a 13-week post-treatment evaluation period and in France, participants not continuing treatment were to enter a 26-week post-treatment follow-up period.	CS6-Volanesorsen n=14 Participants Participants with FCS rolling over from the ISIS 304801-CS6 (NCT02211209) index study after receiving volanesorsen, were to receive 300 mg of volanesorsen as a single SC injection once weekly for Weeks 1-52 of this study. Participants were allowed dose adjustment/dose reduction based on monitoring rules. Following the Week 52 visit, participants had the option of participating in an expanded access program or continuing treatment with 300 mg of volanesorsen as a single SC injection once-weekly for up to an additional 52 weeks (Weeks 53-104) and in France participants, up to an additional 104 weeks for total of 156 weeks of treatment (Weeks 105 to Week 156) of this study until an expanded access program was approved and available in their country. Participants who were not participating in an expanded access program were to enter a 13-week post-treatment evaluation period and in France, participants not continuing treatment were to enter a 26-week post-treatment follow-up period.	CS16-Volanesorsen n=3 Participants Participants with FCS rolling over from the ISIS 304801-CS16 (NCT02300233) index study after receiving volanesorsen, were to receive 300 mg of volanesorsen as a single SC injection once weekly for Weeks 1-52 of this study. Participants were allowed dose adjustment/dose reduction based on monitoring rules. Following the Week 52 visit, participants had the option of participating in an expanded access program or continuing treatment with 300 mg of volanesorsen as a single SC injection once-weekly for up to an additional 52 weeks (Weeks 53-104) and in France participants, up to an additional 104 weeks for total of 156 weeks of treatment (Weeks 105 to Week 156) of this study until an expanded access program was approved and available in their country. Participants who were not participating in an expanded access program were to enter a 13-week post-treatment evaluation period and in France, participants not continuing treatment were to enter a 26-week post-treatment follow-up period.
Mean Percent Change From Baseline in Fasting Triglyceride (TG) Percent Change at Month 3	-59.8 percent change Standard Deviation 37.0	-49.2 percent change Standard Deviation 34.8	-64.9 percent change Standard Deviation 9.1
Mean Percent Change From Baseline in Fasting Triglyceride (TG) Percent Change at Month 6	-45.5 percent change Standard Deviation 42.9	-54.8 percent change Standard Deviation 23.8	-43.0 percent change Standard Deviation 19.7
Mean Percent Change From Baseline in Fasting Triglyceride (TG) Percent Change at Month 12	-36.3 percent change Standard Deviation 44.2	-35.1 percent change Standard Deviation 45.6	-41.6 percent change Standard Deviation 36.3

PRIMARY outcome

Timeframe: From first dose of study drug to end of follow-up period [Up to Week 182]

Population: Safety Set included all participants who were enrolled and received at least one dose of study drug.

An adverse event (AE) was defined as any unfavorable and unintended sign (including a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the study or use of investigational drug product, whether or not the AE was considered related to the investigational drug product. A TEAE was defined as any AE starting or getting worse on or after the first dose of the study drug.

Outcome measures

Outcome measures
Measure	Treatment-naïve Group n=51 Participants Treatment naïve group included combined group of ISIS 304801-CS7 (CS7-New) study participant and participant on placebo in index studies (ISIS 304801-CS6- Placebo \[NCT02211209\] and ISIS 304801-CS16-Placebo \[NCT02300233\]), were to receive 300 mg of volanesorsen as a single SC injection once weekly for Weeks 1-52 of this study. Participants were allowed dose adjustment/dose reduction based on monitoring rules. Following the Week 52 visit, participants had the option of participating in an expanded access program or continuing treatment with 300 mg of volanesorsen as a single SC injection once-weekly for up to an additional 52 weeks (Weeks 53-104) and in France participants, up to an additional 104 weeks for total of 156 weeks of treatment (Weeks 105 to Week 156) of this study until an expanded access program was approved and available in their country. Participants who were not participating in an expanded access program were to enter a 13-week post-treatment evaluation period and in France, participants not continuing treatment were to enter a 26-week post-treatment follow-up period.	CS6-Volanesorsen n=14 Participants Participants with FCS rolling over from the ISIS 304801-CS6 (NCT02211209) index study after receiving volanesorsen, were to receive 300 mg of volanesorsen as a single SC injection once weekly for Weeks 1-52 of this study. Participants were allowed dose adjustment/dose reduction based on monitoring rules. Following the Week 52 visit, participants had the option of participating in an expanded access program or continuing treatment with 300 mg of volanesorsen as a single SC injection once-weekly for up to an additional 52 weeks (Weeks 53-104) and in France participants, up to an additional 104 weeks for total of 156 weeks of treatment (Weeks 105 to Week 156) of this study until an expanded access program was approved and available in their country. Participants who were not participating in an expanded access program were to enter a 13-week post-treatment evaluation period and in France, participants not continuing treatment were to enter a 26-week post-treatment follow-up period.	CS16-Volanesorsen n=3 Participants Participants with FCS rolling over from the ISIS 304801-CS16 (NCT02300233) index study after receiving volanesorsen, were to receive 300 mg of volanesorsen as a single SC injection once weekly for Weeks 1-52 of this study. Participants were allowed dose adjustment/dose reduction based on monitoring rules. Following the Week 52 visit, participants had the option of participating in an expanded access program or continuing treatment with 300 mg of volanesorsen as a single SC injection once-weekly for up to an additional 52 weeks (Weeks 53-104) and in France participants, up to an additional 104 weeks for total of 156 weeks of treatment (Weeks 105 to Week 156) of this study until an expanded access program was approved and available in their country. Participants who were not participating in an expanded access program were to enter a 13-week post-treatment evaluation period and in France, participants not continuing treatment were to enter a 26-week post-treatment follow-up period.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	51 Participants	14 Participants	3 Participants

Adverse Events

Treatment-naïve Group

Serious events: 13 serious events

Other events: 51 other events

Deaths: 0 deaths

CS6-Volanesorsen

Serious events: 2 serious events

Other events: 14 other events

Deaths: 0 deaths

CS16-Volanesorsen

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Akcea Therapeutics

Phone: 617-207-0289

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
Publication restrictions are in place

Restriction type: OTHER

Measure	Treatment-naïve Group n=51 participants at risk Treatment naïve group included combined group of ISIS 304801-CS7 (CS7-New) study participant and participant on placebo in index studies (ISIS 304801-CS6- Placebo \[NCT02211209\] and ISIS 304801-CS16-Placebo \[NCT02300233\]), were to receive 300 mg of volanesorsen as a single SC injection once weekly for Weeks 1-52 of this study. Participants were allowed dose adjustment/dose reduction based on monitoring rules. Following the Week 52 visit, participants had the option of participating in an expanded access program or continuing treatment with 300 mg of volanesorsen as a single SC injection once-weekly for up to an additional 52 weeks (Weeks 53-104) and in France participants, up to an additional 104 weeks for total of 156 weeks of treatment (Weeks 105 to Week 156) of this study until an expanded access program was approved and available in their country. Participants who were not participating in an expanded access program were to enter a 13-week post-treatment evaluation period and in France, participants not continuing treatment were to enter a 26-week post-treatment follow-up period.	CS6-Volanesorsen n=14 participants at risk Participants with FCS rolling over from the ISIS 304801-CS6 (NCT02211209) index study after receiving volanesorsen, were to receive 300 mg of volanesorsen as a single SC injection once weekly for Weeks 1-52 of this study. Participants were allowed dose adjustment/dose reduction based on monitoring rules. Following the Week 52 visit, participants had the option of participating in an expanded access program or continuing treatment with 300 mg of volanesorsen as a single SC injection once-weekly for up to an additional 52 weeks (Weeks 53-104) and in France participants, up to an additional 104 weeks for total of 156 weeks of treatment (Weeks 105 to Week 156) of this study until an expanded access program was approved and available in their country. Participants who were not participating in an expanded access program were to enter a 13-week post-treatment evaluation period and in France, participants not continuing treatment were to enter a 26-week post-treatment follow-up period.	CS16-Volanesorsen n=3 participants at risk Participants with FCS rolling over from the ISIS 304801-CS16 (NCT02300233) index study after receiving volanesorsen, were to receive 300 mg of volanesorsen as a single SC injection once weekly for Weeks 1-52 of this study. Participants were allowed dose adjustment/dose reduction based on monitoring rules. Following the Week 52 visit, participants had the option of participating in an expanded access program or continuing treatment with 300 mg of volanesorsen as a single SC injection once-weekly for up to an additional 52 weeks (Weeks 53-104) and in France participants, up to an additional 104 weeks for total of 156 weeks of treatment (Weeks 105 to Week 156) of this study until an expanded access program was approved and available in their country. Participants who were not participating in an expanded access program were to enter a 13-week post-treatment evaluation period and in France, participants not continuing treatment were to enter a 26-week post-treatment follow-up period.
Gastrointestinal disorders Pancreatitis	3.9% 2/51 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.	0.00% 0/14 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.	0.00% 0/3 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.
Gastrointestinal disorders Pancreatitis acute	3.9% 2/51 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.	0.00% 0/14 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.	0.00% 0/3 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.
Gastrointestinal disorders Pancreatitis chronic	0.00% 0/51 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.	0.00% 0/14 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.	33.3% 1/3 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.
Blood and lymphatic system disorders Thrombocytopenia	5.9% 3/51 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.	0.00% 0/14 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.	33.3% 1/3 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Arthritis	2.0% 1/51 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.	0.00% 0/14 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.	0.00% 0/3 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	2.0% 1/51 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.	0.00% 0/14 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.	0.00% 0/3 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/51 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.	7.1% 1/14 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.	0.00% 0/3 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Tendon calcification	2.0% 1/51 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.	0.00% 0/14 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.	0.00% 0/3 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.
General disorders Influenza like illness	2.0% 1/51 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.	0.00% 0/14 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.	0.00% 0/3 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.
Infections and infestations Diverticulitis	2.0% 1/51 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.	0.00% 0/14 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.	0.00% 0/3 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.
Infections and infestations Urinary tract infection	2.0% 1/51 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.	0.00% 0/14 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.	0.00% 0/3 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.
Injury, poisoning and procedural complications Clavicle fracture	0.00% 0/51 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.	0.00% 0/14 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.	33.3% 1/3 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.
Investigations Haemoglobin decreased	2.0% 1/51 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.	0.00% 0/14 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.	0.00% 0/3 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.
Metabolism and nutrition disorders Diabetes mellitus inadequate control	2.0% 1/51 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.	0.00% 0/14 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.	0.00% 0/3 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	2.0% 1/51 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.	0.00% 0/14 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.	0.00% 0/3 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.
Renal and urinary disorders Focal segmental glomerulosclerosis	0.00% 0/51 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.	7.1% 1/14 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.	0.00% 0/3 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.
Reproductive system and breast disorders Ovarian cyst	2.0% 1/51 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.	0.00% 0/14 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.	0.00% 0/3 • From first dose of study drug to end of follow-up period [Up to Week 182] Safety Set included all participants who were enrolled and received at least one dose of study drug.