The Approach Open Label Study: A Study of Volanesorsen (F... | NCT02658175

NCT02658175

ID	Type	Description	Link
2015-003755-21	EudraCT Number

Status Module

Sponsor/Collaborators Module

Name	Class
Ionis Pharmaceuticals, Inc.	INDUSTRY

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Treatment-naïve Group	Experimental	Treatment naïve group included combined group of ISIS 304801-CS7 (CS7-New) study participant and participant on placebo in index studies (ISIS 304801-CS6 [NCT02211209] and ISIS 304801-CS16 [NCT02300233]), were to receive 300 mg of volanesorsen as single SC once weekly for Weeks 1-52 of this study. Participants were allowed dose adjustment/dose reduction based on monitoring rules. Following Week 52 visit, participants had option of participating in expanded access program or continuing treatment with 300 mg of volanesorsen as single SC once-weekly for up to additional 52 weeks (Weeks 53-104) and in France participants, up to additional 104 weeks for total of 156 weeks (Weeks 105 to Week 156) until expanded access program was approved and available in their country. Participants who were not participating in expanded access program were to enter 13-week post-treatment (PT) evaluation period and in France, participants not continuing treatment were to enter 26-week PT follow-up period.	Drug: Volanesorsen
CS6-Volanesorsen	Experimental	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.	Drug: Volanesorsen

Name	Type	Description	Arm Group Labels	Other Names
Volanesorsen	Drug	300 mg volanesorsen administered via SC injection.	CS16-Volanesorsen CS6-Volanesorsen Treatment-naïve Group

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Mean Percent Change From Baseline in Fasting Triglyceride (TG)	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.	Baseline and Months 3, 6, and 12
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	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.	From first dose of study drug to end of follow-up period [Up to Week 182]

Eligibility Module

Contacts/Locations Module

Facility	Status	City	State	ZIP	Country	Contacts
IONIS Investigative Site		Huntington Beach	California	94143	United States
IONIS Investigative Site

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	May 1, 2019	Aug 2, 2021

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

IONIS-APOCIIIRx
ISIS 304801

FG00051 subjects
FG00114 subjects
FG0023 subjects

Full Analysis Set (FAS) included all participants who were enrolled and received at least one dose of study drug and who had an open-label study baseline triglyceride (TG) assessment.

Arm/Group Information

ID	Title	Description
BG000	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 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.
BG001	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.
BG002	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.
BG003	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00047± 14 BG00148± 14 BG00248± 11 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00034 BG0017 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0002 BG0010 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Race

Title	Measurements
White	BG00039 BG00111 BG002

Fasting Triglyceride (TG)

Mean

Standard Deviation

milligrams per decilitre (mg/dL)

Title

Denominators

Categories

Title	Measurements
	BG0002341± 1193 BG0011523± 946 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Mean Percent Change From Baseline in Fasting Triglyceride (TG)

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.

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.

Posted

Mean

Standard Deviation

percent change

Baseline and Months 3, 6, and 12

ID	Title	Description
OG000	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 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.
OG001	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.
OG002	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.

Units	Counts
Participants	OG00051 OG00114 OG0023

Title

Denominators

Categories

Percent Change at Month 3

- ParticipantsOG00047
- ParticipantsOG00114
- ParticipantsOG0023

Title	Measurements

Primary

Number of Participants With Treatment-emergent Adverse Events (TEAEs)

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.

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

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	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 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.

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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 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.	51	13	51	51	51
EG001	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.	14	2	14	14	14
EG002	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.	3	2	3	3	3

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Pancreatitis	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0002 affected51 at risk EG0010 affected14 at risk EG0020 affected3 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0002 affected51 at risk EG0010 affected14 at risk EG0020 affected3 at risk
Pancreatitis chronic	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0010 affected14 at risk EG0021 affected3 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (19.1)	Systematic Assessment	EG0003 affected51 at risk EG0010 affected14 at risk EG0021 affected3 at risk
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected51 at risk EG0010 affected14 at risk EG0020 affected3 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected51 at risk EG0010 affected14 at risk EG0020 affected3 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Tendon calcification	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected51 at risk EG0010 affected14 at risk EG0020 affected3 at risk
Influenza like illness	General disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected51 at risk EG0010 affected14 at risk EG0020 affected3 at risk
Diverticulitis	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0001 affected51 at risk EG0010 affected14 at risk EG0020 affected3 at risk
Urinary tract infection	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0001 affected51 at risk EG0010 affected14 at risk EG0020 affected3 at risk
Clavicle fracture	Injury, poisoning and procedural complications	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0010 affected14 at risk EG0021 affected3 at risk
Haemoglobin decreased	Investigations	MedDRA (19.1)	Systematic Assessment	EG0001 affected51 at risk EG0010 affected14 at risk EG0020 affected3 at risk
Diabetes mellitus inadequate control	Metabolism and nutrition disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected51 at risk EG0010 affected14 at risk EG0020 affected3 at risk
Abortion spontaneous	Pregnancy, puerperium and perinatal conditions	MedDRA (19.1)	Systematic Assessment	EG0001 affected51 at risk EG0010 affected14 at risk EG0020 affected3 at risk
Focal segmental glomerulosclerosis	Renal and urinary disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Ovarian cyst	Reproductive system and breast disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected51 at risk EG0010 affected14 at risk EG0020 affected3 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Injection site erythema	General disorders	MedDRA (19.1)	Systematic Assessment	EG00036 affected51 at risk EG0017 affected14 at risk EG0021 affected3 at risk
Injection site pain	General disorders	MedDRA (19.1)	Systematic Assessment	EG00021 affected51 at risk EG0013 affected14 at risk EG0020 affected3 at risk
Injection site swelling	General disorders	MedDRA (19.1)	Systematic Assessment	EG00014 affected51 at risk EG0015 affected14 at risk EG0020 affected3 at risk
Injection site pruritus	General disorders	MedDRA (19.1)	Systematic Assessment	EG00011 affected51 at risk EG0014 affected14 at risk EG0020 affected3 at risk
Injection site discolouration	General disorders	MedDRA (19.1)	Systematic Assessment	EG00012 affected51 at risk EG0011 affected14 at risk EG0021 affected3 at risk
Injection site induration	General disorders	MedDRA (19.1)	Systematic Assessment	EG00011 affected51 at risk EG0012 affected14 at risk EG0021 affected3 at risk
Pyrexia	General disorders	MedDRA (19.1)	Systematic Assessment	EG00011 affected51 at risk EG0012 affected14 at risk EG0020 affected3 at risk
Fatigue	General disorders	MedDRA (19.1)	Systematic Assessment	EG0007 affected51 at risk EG0013 affected14 at risk EG0020 affected3 at risk
Chills	General disorders	MedDRA (19.1)	Systematic Assessment	EG0006 affected51 at risk EG0013 affected14 at risk EG0020 affected3 at risk
Asthenia	General disorders	MedDRA (19.1)	Systematic Assessment	EG0003 affected51 at risk EG0012 affected14 at risk EG0022 affected3 at risk
Injection site bruising	General disorders	MedDRA (19.1)	Systematic Assessment	EG0005 affected51 at risk EG0012 affected14 at risk EG0020 affected3 at risk
Injection site haematoma	General disorders	MedDRA (19.1)	Systematic Assessment	EG0005 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Injection site oedema	General disorders	MedDRA (19.1)	Systematic Assessment	EG0005 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Injection site haemorrhage	General disorders	MedDRA (19.1)	Systematic Assessment	EG0003 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Pain	General disorders	MedDRA (19.1)	Systematic Assessment	EG0002 affected51 at risk EG0012 affected14 at risk EG0020 affected3 at risk
Injection site hypoaesthesia	General disorders	MedDRA (19.1)	Systematic Assessment	EG0003 affected51 at risk EG0010 affected14 at risk EG0020 affected3 at risk
Injection site reaction	General disorders	MedDRA (19.1)	Systematic Assessment	EG0003 affected51 at risk EG0010 affected14 at risk EG0020 affected3 at risk
Injection site urticaria	General disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected51 at risk EG0012 affected14 at risk EG0020 affected3 at risk
Peripheral swelling	General disorders	MedDRA (19.1)	Systematic Assessment	EG0003 affected51 at risk EG0010 affected14 at risk EG0020 affected3 at risk
Injection site dryness	General disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Cyst	General disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Feeling hot	General disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Influenza like illness	General disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Injection site mass	General disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Local swelling	General disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Non-cardiac chest pain	General disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Nasopharyngitis	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG00021 affected51 at risk EG0014 affected14 at risk EG0020 affected3 at risk
Influenza	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0008 affected51 at risk EG0015 affected14 at risk EG0020 affected3 at risk
Urinary tract infection	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0008 affected51 at risk EG0013 affected14 at risk EG0020 affected3 at risk
Bronchitis	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0005 affected51 at risk EG0012 affected14 at risk EG0021 affected3 at risk
Gastroenteritis	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0005 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Ear infection	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0004 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Sinusitis	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0004 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Atypical pneumonia	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Fungal infection	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0010 affected14 at risk EG0021 affected3 at risk
Onychomycosis	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Tooth infection	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG00014 affected51 at risk EG0015 affected14 at risk EG0023 affected3 at risk
Nausea	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG00011 affected51 at risk EG0014 affected14 at risk EG0021 affected3 at risk
Vomiting	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0009 affected51 at risk EG0013 affected14 at risk EG0020 affected3 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0006 affected51 at risk EG0012 affected14 at risk EG0021 affected3 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0007 affected51 at risk EG0010 affected14 at risk EG0020 affected3 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0004 affected51 at risk EG0012 affected14 at risk EG0020 affected3 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0005 affected51 at risk EG0010 affected14 at risk EG0020 affected3 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0004 affected51 at risk EG0010 affected14 at risk EG0020 affected3 at risk
Constipation	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0002 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Abdominal tenderness	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Anal haemorrhage	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Diverticulum	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Gingival bleeding	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Pancreatitis chronic	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0010 affected14 at risk EG0021 affected3 at risk
Periodontal disease	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Toothache	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG00010 affected51 at risk EG0012 affected14 at risk EG0020 affected3 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0007 affected51 at risk EG0013 affected14 at risk EG0020 affected3 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0007 affected51 at risk EG0012 affected14 at risk EG0020 affected3 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0005 affected51 at risk EG0012 affected14 at risk EG0020 affected3 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0003 affected51 at risk EG0012 affected14 at risk EG0020 affected3 at risk
Pain in jaw	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0002 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Joint swelling	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Rotator cuff syndrome	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Plantar fasciitis	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Seronegative arthritis	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Headache	Nervous system disorders	MedDRA (19.1)	Systematic Assessment	EG00012 affected51 at risk EG0014 affected14 at risk EG0020 affected3 at risk
Dizziness	Nervous system disorders	MedDRA (19.1)	Systematic Assessment	EG0005 affected51 at risk EG0012 affected14 at risk EG0020 affected3 at risk
Paraesthesia	Nervous system disorders	MedDRA (19.1)	Systematic Assessment	EG0003 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Hypoaesthesia	Nervous system disorders	MedDRA (19.1)	Systematic Assessment	EG0003 affected51 at risk EG0010 affected14 at risk EG0020 affected3 at risk
Sciatica	Nervous system disorders	MedDRA (19.1)	Systematic Assessment	EG0002 affected51 at risk EG0010 affected14 at risk EG0021 affected3 at risk
Polyneuropathy	Nervous system disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Systematic Assessment	EG0009 affected51 at risk EG0013 affected14 at risk EG0020 affected3 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Systematic Assessment	EG0009 affected51 at risk EG0012 affected14 at risk EG0020 affected3 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Systematic Assessment	EG0003 affected51 at risk EG0012 affected14 at risk EG0020 affected3 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Systematic Assessment	EG0003 affected51 at risk EG0010 affected14 at risk EG0020 affected3 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Systematic Assessment	EG0003 affected51 at risk EG0010 affected14 at risk EG0020 affected3 at risk
Bronchitis chronic	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Systematic Assessment	EG0003 affected51 at risk EG0010 affected14 at risk EG0020 affected3 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Platelet count decreased	Investigations	MedDRA (19.1)	Systematic Assessment	EG00015 affected51 at risk EG0012 affected14 at risk EG0020 affected3 at risk
Alanine aminotransferase increased	Investigations	MedDRA (19.1)	Systematic Assessment	EG0005 affected51 at risk EG0010 affected14 at risk EG0020 affected3 at risk
Aspartate aminotransferase increased	Investigations	MedDRA (19.1)	Systematic Assessment	EG0004 affected51 at risk EG0010 affected14 at risk EG0020 affected3 at risk
Haemoglobin decreased	Investigations	MedDRA (19.1)	Systematic Assessment	EG0003 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Haematocrit decreased	Investigations	MedDRA (19.1)	Systematic Assessment	EG0003 affected51 at risk EG0010 affected14 at risk EG0020 affected3 at risk
Cold agglutinins	Investigations	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0010 affected14 at risk EG0021 affected3 at risk
Fibrin D dimer increased	Investigations	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (19.1)	Systematic Assessment	EG0009 affected51 at risk EG0011 affected14 at risk EG0022 affected3 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA (19.1)	Systematic Assessment	EG0003 affected51 at risk EG0012 affected14 at risk EG0020 affected3 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected51 at risk EG0010 affected14 at risk EG0021 affected3 at risk
Microcytic anaemia	Blood and lymphatic system disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0010 affected14 at risk EG0021 affected3 at risk
Ecchymosis	Skin and subcutaneous tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0004 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected51 at risk EG0012 affected14 at risk EG0022 affected3 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0003 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected51 at risk EG0012 affected14 at risk EG0020 affected3 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0002 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Night sweats	Skin and subcutaneous tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Rash vesicular	Skin and subcutaneous tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0010 affected14 at risk EG0021 affected3 at risk
Skin hypertrophy	Skin and subcutaneous tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Swelling face	Skin and subcutaneous tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Haematoma	Vascular disorders	MedDRA (19.1)	Systematic Assessment	EG0004 affected51 at risk EG0010 affected14 at risk EG0020 affected3 at risk
Haemorrhage	Vascular disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected51 at risk EG0012 affected14 at risk EG0020 affected3 at risk
Flushing	Vascular disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Hot flush	Vascular disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Hypertension	Vascular disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Proteinuria	Renal and urinary disorders	MedDRA (19.1)	Systematic Assessment	EG0004 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Albuminuria	Renal and urinary disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Renal cyst	Renal and urinary disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Depression	Psychiatric disorders	MedDRA (19.1)	Systematic Assessment	EG0002 affected51 at risk EG0010 affected14 at risk EG0022 affected3 at risk
Anxiety	Psychiatric disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected51 at risk EG0010 affected14 at risk EG0022 affected3 at risk
Insomnia	Psychiatric disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA (19.1)	Systematic Assessment	EG0003 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Ligament rupture	Injury, poisoning and procedural complications	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Breast mass	Reproductive system and breast disorders	MedDRA (19.1)	Systematic Assessment	EG0003 affected51 at risk EG0010 affected14 at risk EG0020 affected3 at risk
Ovarian cyst	Reproductive system and breast disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Testicular cyst	Reproductive system and breast disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Vision blurred	Eye disorders	MedDRA (19.1)	Systematic Assessment	EG0003 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Type 2 diabetes mellitus	Metabolism and nutrition disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Vitamin D deficiency	Metabolism and nutrition disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Hypothyroidism	Endocrine disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected51 at risk EG0010 affected14 at risk EG0022 affected3 at risk
Hyperthyroidism	Endocrine disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0010 affected14 at risk EG0021 affected3 at risk
Immunisation reaction	Immune system disorders	MedDRA (19.1)	Systematic Assessment	EG0002 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Vertigo	Ear and labyrinth disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk
Device failure	Product Issues	MedDRA (19.1)	Systematic Assessment	EG0000 affected51 at risk EG0011 affected14 at risk EG0020 affected3 at risk

ID	Term
C538489	Familial hyperchylomicronemia syndrome
D008072	Hyperlipoproteinemia Type I

Ancestor Terms

ID	Term
D008052	Lipid Metabolism, Inborn Errors
D008661	Metabolism, Inborn Errors
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D006951	Hyperlipoproteinemias
D006949	Hyperlipidemias
D050171	Dyslipidemias
D052439	Lipid Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases

ID	Term
C000593612	ISIS 304801