A Study to Investigate the Safety and Effectiveness of Di... | NCT01919164

ID	Type	Description	Link
2011-003059-20	EudraCT Number

Name	Class
Nordic Bioscience A/S	INDUSTRY

Label	Type	Description	Intervention Names
Placebo	Placebo Comparator	Participants received Placebo matched to Sprifermin as intra-articular injection once every week for 3 consecutive weeks for 4 cycles, that is at week 0, 1, 2 in Cycle 1; at week 26, 27, 28 in Cycle 2; at week 52, 53, 54 in Cycle 3 and at week 78, 79, 80 in Cycle 4 at interval of 6 months.	Drug: Placebo
Sprifermin (AS902330) 30 mcg/placebo - 2 Cycles	Experimental	Participants received Sprifermin 30 mcg as intra-articular injection once every week for 3 consecutive weeks for 2 alternative cycles, that is at week 0, 1, 2 in Cycle 1 and at week 52, 53, 54 in Cycle 3; and received placebo matched to Sprifermin once every week for 3 consecutive weeks for 2 alternative cycles, that is at week 26, 27, 28 in Cycle 2 and at week 78, 79, 80 in Cycle 4 at interval of 6 months.	Drug: Sprifermin Drug: Placebo
Sprifermin (AS902330) 30 mcg- 4 Cycles	Experimental	Participants received Sprifermin 30 micrograms (mcg) as intra-articular injection once every week for 3 consecutive weeks for 4 cycles, that is at week 0, 1, 2 in Cycle 1; at week 26, 27, 28 in Cycle 2; at week 52, 53, 54 in Cycle 3 and at week 78, 79, 80 in Cycle 4 at interval of 6 months.	Drug: Sprifermin
Sprifermin (AS902330) 100 mcg/Placebo (2 cycles)	Experimental	Participants received Sprifermin 100 mcg as intra-articular injection once every week for 3 consecutive weeks for 2 alternative cycles, that is at week 0, 1, 2 in Cycle 1 and at week 52, 53, 54 in Cycle 3; and received placebo matched to Sprifermin once every week for 3 consecutive weeks for 2 alternative cycles, that is at week 26, 27, 28 in Cycle 2 and at week 78, 79, 80 in Cycle 4 at interval of 6 months.

Name	Type	Description	Arm Group Labels	Other Names
Sprifermin	Drug	Participants received Sprifermin as intra-articular injection.	Sprifermin (AS902330) 100 mcg- 4 Cycles Sprifermin (AS902330) 100 mcg/Placebo (2 cycles)

Measure	Description	Time Frame
Change From Baseline in Cartilage Thickness in the Total Femorotibial Joint as Evaluated by Quantitative Magnetic Resonance Imaging (qMRI) at Year 2	The change in cartilage thickness at 2 years was calculated based on quantitative magnetic resonance imaging (qMRI).	Baseline, Year 2 (Week 104)

Measure	Description	Time Frame
Changes From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale, Stiffness Subscale, Physical Function Subscale and Total Score at Week 52, Week 78 and Week 104	WOMAC pain subscale consists of 5 questions (Likert Scale) relating to pain. Sum of items of pain subscale ranges from 0-11. Higher scores=worse pain. Stiffness subscale consists of 2 questions relating articular function. Sum of items of stiffness subscale ranges from 0-8. Higher scores=worse function. Physical function subscale consists of 17 question relating to physical activities. Sum of items of physical function subscale ranges from 0-68. Higher scores= worse functional limitations. Each sub-scale is directly transformed into a 0-100 scale, where higher score indicates worse condition. WOMAC total score(24questions) is sum of total subscales which was directly transformed into score range from 0-100. Higher scores=worse condition. Negative value in change is indicative of improvement.

Name	Affiliation	Role
Medical Responsible, MD	Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Research site		Lakewood	Colorado		United States
Research site

PubMed Identifier	Type	Citation	Retractions
39734047	Derived	Conaghan PG, Katz N, Hunter DJ, Guermazi A, Hochberg MC, Somberg K, Clive J, Knight C, Johnson M, Zhao L, Goel N. Exploring a novel outcome measure of symptom progression in knee osteoarthritis utilizing a large randomized trial. Osteoarthritis Cartilage. 2025 Mar;33(3):383-390. doi: 10.1016/j.joca.2024.12.003. Epub 2024 Dec 28.
39286575

Label	URL
Trial Awareness and Transparency website Scope	View source

ID	Title	Description
FG000	Placebo	Participants received Placebo matched to Sprifermin as intra-articular injection once every week for 3 consecutive weeks for 4 cycles, that is at week 0, 1, 2 in Cycle 1; at week 26, 27, 28 in Cycle 2; at week 52, 53, 54 in Cycle 3 and at week 78, 79, 80 in Cycle 4 at interval of 6 months.
FG001

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Mar 5, 2013	Jun 18, 2020

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

Change From Baseline in Cartilage Thickness in the Total Femorotibial Joint as Evaluated by Quantitative Magnetic Resonance Imaging (qMRI) at Year 2

The change in cartilage thickness at 2 years was calculated based on quantitative magnetic resonance imaging (qMRI).

Modified intent to treat (ITT) analysis set included all randomized participants that is, only planned treatment regimen was used and who had a baseline, at least 1 post-treatment qMRI assessment available in double-blind placebo-controlled part. Here "Number of Participants analyzed" = participants evaluable for this outcome measure.

Posted

Mean

Standard Deviation

millimeters

Baseline, Year 2 (Week 104)

ID	Title	Description
OG000	Placebo	Participants received Placebo matched to Sprifermin as intra-articular injection once every week for 3 consecutive weeks for 4 cycles, that is at week 0, 1, 2 in Cycle 1; at week 26, 27, 28 in Cycle 2; at week 52, 53, 54 in Cycle 3 and at week 78, 79, 80 in Cycle 4 at interval of 6 months.
OG001	Sprifermin (AS902330) 30 mcg/Placebo - 2 Cycles	Participants received Sprifermin 30 micrograms (mcg) as intra-articular injection once every week for 3 consecutive weeks for 2 alternative cycles, that is at week 0, 1, 2 in Cycle 1 and at week 52, 53, 54 in Cycle 3; and received placebo matched to Sprifermin once every week for 3 consecutive weeks for 2 alternative cycles, that is at week 26, 27, 28 in Cycle 2 and at week 78, 79, 80 in Cycle 4 at interval of 6 months.
OG002	Sprifermin (AS902330) 30 mcg- 4 Cycles	Participants received Sprifermin 30 micrograms (mcg) as intra-articular injection once every week for 3 consecutive weeks for 4 cycles, that is at week 0, 1, 2 in Cycle 1; at week 26, 27, 28 in Cycle 2; at week 52, 53, 54 in Cycle 3 and at week 78, 79, 80 in Cycle 4 at interval of 6 months.
OG003	Sprifermin (AS902330) 100 mcg/Placebo (2 Cycles)	Participants received Sprifermin 100 mcg as intra-articular injection once every week for 3 consecutive weeks for 2 alternative cycles, that is at week 0, 1, 2 in Cycle 1 and at week 52, 53, 54 in Cycle 3; and received placebo matched to Sprifermin once every week for 3 consecutive weeks for 2 alternative cycles, that is at week 26, 27, 28 in Cycle 2 and at week 78, 79, 80 in Cycle 4 at interval of 6 months.
OG004	Sprifermin (AS902330) 100 mcg- 4 Cycles	Participants received Sprifermin 100 mcg as intra-articular injection once every week for 3 consecutive weeks for 4 cycles, that is at week 0, 1, 2 in Cycle 1; at week 26, 27, 28 in Cycle 2; at week 52, 53, 54 in Cycle 3 and at week 78, 79, 80 in Cycle 4 at interval of 6 months.

Units	Counts
Participants	OG00083 OG00192 OG00283 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-0.02± 0.07 OG001-0.01± 0.07 OG0020.00± 0.07 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Descriptive statistics was provided for primary endpoint.					Mean Difference (Final Values)	0.01			2-Sided	95	-0.01	0.03					Superiority
OG000 OG002	Descriptive statistics was provided for primary endpoint.

Secondary

Changes From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale, Stiffness Subscale, Physical Function Subscale and Total Score at Week 52, Week 78 and Week 104

WOMAC pain subscale consists of 5 questions (Likert Scale) relating to pain. Sum of items of pain subscale ranges from 0-11. Higher scores=worse pain. Stiffness subscale consists of 2 questions relating articular function. Sum of items of stiffness subscale ranges from 0-8. Higher scores=worse function. Physical function subscale consists of 17 question relating to physical activities. Sum of items of physical function subscale ranges from 0-68. Higher scores= worse functional limitations. Each sub-scale is directly transformed into a 0-100 scale, where higher score indicates worse condition. WOMAC total score(24questions) is sum of total subscales which was directly transformed into score range from 0-100. Higher scores=worse condition. Negative value in change is indicative of improvement.

Intention-to-Treat (ITT) analysis set included all participants randomly allocated to a treatment, based on the intention to treat "as randomized" principle. Here "Number of Participants analyzed" = participants evaluable for this outcome measure and "Number analyzed" included those who were evaluable at specified timepoints.

Posted

Mean

Standard Deviation

score on a scale

Baseline, Week 52, Week 78 and Week 104

ID	Title	Description
OG000	Placebo	Participants received Placebo matched to Sprifermin as intra-articular injection once every week for 3 consecutive weeks for 4 cycles, that is at week 0, 1, 2 in Cycle 1; at week 26, 27, 28 in Cycle 2; at week 52, 53, 54 in Cycle 3 and at week 78, 79, 80 in Cycle 4 at interval of 6 months.

Secondary

Change From Baseline in the 20-meter Walk Test at Week 12, 26, 38, 52, 64, 78, 90 and 104

The 20-meter walk test is an objective test of physical function which consists of measuring the time needed for the participant to walk 20 meters at a normal pace. A stopwatch was used for time measurement.

Posted

Mean

Standard Deviation

seconds

Baseline, Week 12, 26, 38, 52, 64, 78, 90 and 104

ID	Title	Description
OG000	Placebo	Participants received Placebo matched to Sprifermin as intra-articular injection once every week for 3 consecutive weeks for 4 cycles, that is at week 0, 1, 2 in Cycle 1; at week 26, 27, 28 in Cycle 2; at week 52, 53, 54 in Cycle 3 and at week 78, 79, 80 in Cycle 4 at interval of 6 months.
OG001	Sprifermin (AS902330) 30 mcg/Placebo - 2 Cycles	Participants received Sprifermin 30 micrograms (mcg) as intra-articular injection once every week for 3 consecutive weeks for 2 alternative cycles, that is at week 0, 1, 2 in Cycle 1 and at week 52, 53, 54 in Cycle 3; and received placebo matched to Sprifermin once every week for 3 consecutive weeks for 2 alternative cycles, that is at week 26, 27, 28 in Cycle 2 and at week 78, 79, 80 in Cycle 4 at interval of 6 months.

Secondary

Change From Baseline in the Patient's Global Assessment (PGA) at Week 12, 26, 38, 52, 64, 78, 90 and 104

The Patient Global Assessment is based on participant's answer to the question "Considering all the ways your osteoarthritis of the knee has affected you during the last 48 Hours, select the number that best describes the impact of your knee osteoarthritis on your daily life", and can take on values between 0-10 (0=None, 10=Extreme), for summaries the values are rescaled to 0-100 by multiplication with 10. Higher scores indicated worsening of condition. A negative value in change in Patient's Global Assessment is indicative of an improvement.

Posted

Mean

Standard Deviation

score on a scale

Baseline, Week 12, 26, 38, 52, 64, 78, 90 and 104

ID	Title	Description
OG000	Placebo	Participants received Placebo matched to Sprifermin as intra-articular injection once every week for 3 consecutive weeks for 4 cycles, that is at week 0, 1, 2 in Cycle 1; at week 26, 27, 28 in Cycle 2; at week 52, 53, 54 in Cycle 3 and at week 78, 79, 80 in Cycle 4 at interval of 6 months.
OG001	Sprifermin (AS902330) 30 mcg/Placebo - 2 Cycles

Secondary

Change From Baseline in Minimal Joint Space Width (mJSW) in the Medial and Lateral Compartments as Evaluated by X-ray at Week 52 and 104

Change in joint space narrowing was visualized with the "fixed flexion" knee radiograph. Determination of joint space narrowing by X-ray is considered to be a semi-quantitative method for assessment of progression of knee Osteoarthritis (OA). X-rays of both the target knee and the contralateral knee were performed. X-rays were read centrally. X-ray images were used to measure mJSW in the medial femorotibial and lateral femorotibial compartments and to determine the participant's baseline Kellgren-Lawrence grades (KLG).

Posted

Mean

Standard Deviation

millimeter

Baseline, Week 52 and 104

ID	Title	Description
OG000	Placebo	Participants received Placebo matched to Sprifermin as intra-articular injection once every week for 3 consecutive weeks for 4 cycles, that is at week 0, 1, 2 in Cycle 1; at week 26, 27, 28 in Cycle 2; at week 52, 53, 54 in Cycle 3 and at week 78, 79, 80 in Cycle 4 at interval of 6 months.
OG001	Sprifermin (AS902330) 30 mcg/Placebo - 2 Cycles	Participants received Sprifermin 30 micrograms (mcg) as intra-articular injection once every week for 3 consecutive weeks for 2 alternative cycles, that is at week 0, 1, 2 in Cycle 1 and at week 52, 53, 54 in Cycle 3; and received placebo matched to Sprifermin once every week for 3 consecutive weeks for 2 alternative cycles, that is at week 26, 27, 28 in Cycle 2 and at week 78, 79, 80 in Cycle 4 at interval of 6 months.

Secondary

Change From Baseline in Cartilage Thickness in the Medial and Lateral Compartments as Well as in the Total Femorotibial Joint

The change in cartilage thickness was calculated based on quantitative magnetic resonance imaging (qMRI).

Modified ITT analysis set was used. Here "Number of Participants analyzed" = participants evaluable for this outcome measure and "Number analyzed" included those who were evaluable at specified timepoints.

Posted

Mean

Standard Deviation

millimeter

Medial and Lateral: Baseline, Week 26, 52, 78 and 104; Total: Baseline, Week 26, 52 and 78

ID	Title	Description
OG000	Placebo	Participants received Placebo matched to Sprifermin as intra-articular injection once every week for 3 consecutive weeks for 4 cycles, that is at week 0, 1, 2 in Cycle 1; at week 26, 27, 28 in Cycle 2; at week 52, 53, 54 in Cycle 3 and at week 78, 79, 80 in Cycle 4 at interval of 6 months.
OG001	Sprifermin (AS902330) 30 mcg/Placebo - 2 Cycles	Participants received Sprifermin 30 micrograms (mcg) as intra-articular injection once every week for 3 consecutive weeks for 2 alternative cycles, that is at week 0, 1, 2 in Cycle 1 and at week 52, 53, 54 in Cycle 3; and received placebo matched to Sprifermin once every week for 3 consecutive weeks for 2 alternative cycles, that is at week 26, 27, 28 in Cycle 2 and at week 78, 79, 80 in Cycle 4 at interval of 6 months.

Secondary

Change From Baseline in Cartilage-Volume in the Medial and Lateral Compartments as Well as in the Total Femorotibial Joint at Week 26, 52, 78 and 104

The change in cartilage volume in the medial and lateral compartments as well as in the total femorotibial joint at Week 26, 52, 78 and 104 was calculated based on qMRI.

Posted

Mean

Standard Deviation

microliter

Baseline, Week 26, 52, 78 and 104

ID	Title	Description
OG000	Placebo	Participants received Placebo matched to Sprifermin as intra-articular injection once every week for 3 consecutive weeks for 4 cycles, that is at week 0, 1, 2 in Cycle 1; at week 26, 27, 28 in Cycle 2; at week 52, 53, 54 in Cycle 3 and at week 78, 79, 80 in Cycle 4 at interval of 6 months.
OG001	Sprifermin (AS902330) 30 mcg/Placebo - 2 Cycles	Participants received Sprifermin 30 micrograms (mcg) as intra-articular injection once every week for 3 consecutive weeks for 2 alternative cycles, that is at week 0, 1, 2 in Cycle 1 and at week 52, 53, 54 in Cycle 3; and received placebo matched to Sprifermin once every week for 3 consecutive weeks for 2 alternative cycles, that is at week 26, 27, 28 in Cycle 2 and at week 78, 79, 80 in Cycle 4 at interval of 6 months.

Secondary

Synovial Fluid Levels of Sprifermin/FGF-18

Levels of sprifermin/FGF-18 in synovial fluid were measured to provide a first estimate of the residence time of sprifermin in the synovial fluid.

Safety analysis set included all participants who received at least 1 dose of study treatment. Arm assignments for participants in Safety Set were based on actual treatment received. Here "Number of Participants analyzed" = participants evaluable for this outcome measure and "Number analyzed" are those who were evaluable at specified timepoint.

Posted

Median

Full Range

picogram/milliliter

Pre-dose at Week 0, 2 hours post-dose at Week 1 and 2 of Cycle 1, 2, 3 and 4 (each cycle is of 28 days)

ID	Title	Description
OG000	Placebo	Participants received Placebo matched to Sprifermin as intra-articular injection once every week for 3 consecutive weeks for 4 cycles, that is at week 0, 1, 2 in Cycle 1; at week 26, 27, 28 in Cycle 2; at week 52, 53, 54 in Cycle 3 and at week 78, 79, 80 in Cycle 4 at interval of 6 months.
OG001	Sprifermin (AS902330) 30 mcg/Placebo - 2 Cycles	Participants received Sprifermin 30 micrograms (mcg) as intra-articular injection once every week for 3 consecutive weeks for 2 alternative cycles, that is at week 0, 1, 2 in Cycle 1 and at week 52, 53, 54 in Cycle 3; and received placebo matched to Sprifermin once every week for 3 consecutive weeks for 2 alternative cycles, that is at week 26, 27, 28 in Cycle 2 and at week 78, 79, 80 in Cycle 4 at interval of 6 months.

Secondary

Serum Levels of Sprifermin/FGF-18

Safety analysis set included all participants who received at least 1 dose of study treatment. Arm assignments for participants in Safety Set were based on actual treatment received.

Posted

Mean

Standard Deviation

picogram/milliliter

Pre-dose at Week 0, 2 hours post-dose at Week 1 and 2 of Cycle 1, 2, 3 and 4 (each cycle is of 28 days)

ID	Title	Description
OG000	Placebo	Participants received Placebo matched to Sprifermin as intra-articular injection once every week for 3 consecutive weeks for 4 cycles, that is at week 0, 1, 2 in Cycle 1; at week 26, 27, 28 in Cycle 2; at week 52, 53, 54 in Cycle 3 and at week 78, 79, 80 in Cycle 4 at interval of 6 months.
OG001	Sprifermin (AS902330) 30 mcg/Placebo - 2 Cycles	Participants received Sprifermin 30 micrograms (mcg) as intra-articular injection once every week for 3 consecutive weeks for 2 alternative cycles, that is at week 0, 1, 2 in Cycle 1 and at week 52, 53, 54 in Cycle 3; and received placebo matched to Sprifermin once every week for 3 consecutive weeks for 2 alternative cycles, that is at week 26, 27, 28 in Cycle 2 and at week 78, 79, 80 in Cycle 4 at interval of 6 months.
OG002	Sprifermin (AS902330) 30 mcg- 4 Cycles	Participants received Sprifermin 30 micrograms (mcg) as intra-articular injection once every week for 3 consecutive weeks for 4 cycles, that is at week 0, 1, 2 in Cycle 1; at week 26, 27, 28 in Cycle 2; at week 52, 53, 54 in Cycle 3 and at week 78, 79, 80 in Cycle 4 at interval of 6 months.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Iron deficiency anaemia	Blood and lymphatic system disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG0031 affected111 at risk EG004
Acute myocardial infarction	Cardiac disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected109 at risk EG0020 affected111 at risk EG003
Angina pectoris	Cardiac disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA version 21.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Atrial flutter	Cardiac disorders	MedDRA version 21.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected109 at risk EG0021 affected111 at risk EG003
Coronary artery stenosis	Cardiac disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected109 at risk EG0022 affected111 at risk EG003
Myocardial infarction	Cardiac disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Angina unstable	Cardiac disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0022 affected111 at risk EG003
Cardiac failure congestive	Cardiac disorders	MedDRA version 21.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected109 at risk EG0021 affected111 at risk EG003
Myocardial ischaemia	Cardiac disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0021 affected111 at risk EG003
Aortic valve stenosis	Cardiac disorders	MedDRA version 21.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Arrhythmia	Cardiac disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Bradycardia	Cardiac disorders	MedDRA version 21.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Cardiac failure	Cardiac disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Cardiomyopathy	Cardiac disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Pericarditis	Cardiac disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Stress cardiomyopathy	Cardiac disorders	MedDRA version 21.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Supraventricular extrasystoles	Cardiac disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Ventricular extrasystoles	Cardiac disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Ventricular tachycardia	Cardiac disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Vertigo	Ear and labyrinth disorders	MedDRA version 21.1	Non-systematic Assessment	EG0001 affected107 at risk EG0011 affected109 at risk EG0020 affected111 at risk EG003
Vertigo positional	Ear and labyrinth disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Inappropriate antidiuretic hormone secretion	Endocrine disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Toxic nodular goitre	Endocrine disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Retinal detachment	Eye disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0021 affected111 at risk EG003
Large intestine polyp	Gastrointestinal disorders	MedDRA version 21.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected109 at risk EG0021 affected111 at risk EG003
Abdominal hernia obstructive	Gastrointestinal disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0021 affected111 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Colitis	Gastrointestinal disorders	MedDRA version 21.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Diverticulum	Gastrointestinal disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Gastric ulcer	Gastrointestinal disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Haemorrhoids	Gastrointestinal disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0021 affected111 at risk EG003
Ileus	Gastrointestinal disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0021 affected111 at risk EG003
Intestinal obstruction	Gastrointestinal disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected109 at risk EG0020 affected111 at risk EG003
Loose tooth	Gastrointestinal disorders	MedDRA version 21.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Pancreatitis acute	Gastrointestinal disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Parotid gland enlargement	Gastrointestinal disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Umbilical hernia	Gastrointestinal disorders	MedDRA version 21.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Chest pain	General disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Malaise	General disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0021 affected111 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Peripheral swelling	General disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0021 affected111 at risk EG003
Cholecystitis	Hepatobiliary disorders	MedDRA version 21.1	Non-systematic Assessment	EG0002 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Cholecystitis acute	Hepatobiliary disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected109 at risk EG0020 affected111 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Bile duct stone	Hepatobiliary disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Cholangitis acute	Hepatobiliary disorders	MedDRA version 21.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Pneumonia	Infections and infestations	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0012 affected109 at risk EG0024 affected111 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA version 21.1	Non-systematic Assessment	EG0001 affected107 at risk EG0011 affected109 at risk EG0020 affected111 at risk EG003
Appendicitis	Infections and infestations	MedDRA version 21.1	Non-systematic Assessment	EG0002 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Bronchitis	Infections and infestations	MedDRA version 21.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected109 at risk EG0021 affected111 at risk EG003
Arthritis bacterial	Infections and infestations	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0021 affected111 at risk EG003
Cellulitis	Infections and infestations	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0021 affected111 at risk EG003
Cystitis	Infections and infestations	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Diverticulitis	Infections and infestations	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Erysipelas	Infections and infestations	MedDRA version 21.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0021 affected111 at risk EG003
Influenza	Infections and infestations	MedDRA version 21.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Lower respiratory tract infection	Infections and infestations	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Otitis media chronic	Infections and infestations	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Sialoadenitis	Infections and infestations	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Tonsillitis	Infections and infestations	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Urosepsis	Infections and infestations	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Meniscus injury	Injury, poisoning and procedural complications	MedDRA version 21.1	Non-systematic Assessment	EG0002 affected107 at risk EG0011 affected109 at risk EG0021 affected111 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA version 21.1	Non-systematic Assessment	EG0002 affected107 at risk EG0010 affected109 at risk EG0021 affected111 at risk EG003
Wrist fracture	Injury, poisoning and procedural complications	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0012 affected109 at risk EG0020 affected111 at risk EG003
Ankle fracture	Injury, poisoning and procedural complications	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected109 at risk EG0020 affected111 at risk EG003
Clavicle fracture	Injury, poisoning and procedural complications	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0021 affected111 at risk EG003
Concussion	Injury, poisoning and procedural complications	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Facial bones fracture	Injury, poisoning and procedural complications	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected109 at risk EG0020 affected111 at risk EG003
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected109 at risk EG0020 affected111 at risk EG003
Foot fracture	Injury, poisoning and procedural complications	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Hand fracture	Injury, poisoning and procedural complications	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Head injury	Injury, poisoning and procedural complications	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Muscle strain	Injury, poisoning and procedural complications	MedDRA version 21.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Pelvic fracture	Injury, poisoning and procedural complications	MedDRA version 21.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Periprosthetic fracture	Injury, poisoning and procedural complications	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Skin injury	Injury, poisoning and procedural complications	MedDRA version 21.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Skin laceration	Injury, poisoning and procedural complications	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected109 at risk EG0020 affected111 at risk EG003
Stress fracture	Injury, poisoning and procedural complications	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0021 affected111 at risk EG003
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Tendon rupture	Injury, poisoning and procedural complications	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Tibia fracture	Injury, poisoning and procedural complications	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0021 affected111 at risk EG003
Toxicity to various agents	Injury, poisoning and procedural complications	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Upper limb fracture	Injury, poisoning and procedural complications	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Wound dehiscence	Injury, poisoning and procedural complications	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0021 affected111 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0021 affected111 at risk EG003
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA version 21.1	Non-systematic Assessment	EG0009 affected107 at risk EG00110 affected109 at risk EG0027 affected111 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA version 21.1	Non-systematic Assessment	EG0003 affected107 at risk EG0012 affected109 at risk EG0023 affected111 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0014 affected109 at risk EG0020 affected111 at risk EG003
Chondropathy	Musculoskeletal and connective tissue disorders	MedDRA version 21.1	Non-systematic Assessment	EG0002 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Lumbar spinal stenosis	Musculoskeletal and connective tissue disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected109 at risk EG0020 affected111 at risk EG003
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Dupuytren's contracture	Musculoskeletal and connective tissue disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0021 affected111 at risk EG003
Foot deformity	Musculoskeletal and connective tissue disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Joint effusion	Musculoskeletal and connective tissue disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected109 at risk EG0020 affected111 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected109 at risk EG0020 affected111 at risk EG003
Spinal column stenosis	Musculoskeletal and connective tissue disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected109 at risk EG0020 affected111 at risk EG003
Spondylolisthesis	Musculoskeletal and connective tissue disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected109 at risk EG0020 affected111 at risk EG003
Synovitis	Musculoskeletal and connective tissue disorders	MedDRA version 21.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Torticollis	Musculoskeletal and connective tissue disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Trigger finger	Musculoskeletal and connective tissue disorders	MedDRA version 21.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Vertebral foraminal stenosis	Musculoskeletal and connective tissue disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected109 at risk EG0020 affected111 at risk EG003
Colon cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0021 affected111 at risk EG003
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0012 affected109 at risk EG0021 affected111 at risk EG003
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 21.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected109 at risk EG0021 affected111 at risk EG003
Renal cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 21.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected109 at risk EG0021 affected111 at risk EG003
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Benign breast neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Benign pancreatic neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 21.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Benign salivary gland neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Bladder transitional cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Carcinoid tumour	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected109 at risk EG0020 affected111 at risk EG003
Carcinoid tumour of the gastrointestinal tract	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected109 at risk EG0020 affected111 at risk EG003
Colon cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0021 affected111 at risk EG003
Diffuse large B-cell lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 21.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Fibroma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 21.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Follicular thyroid cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Gastric cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 21.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Metastases to liver	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0021 affected111 at risk EG003
Metastatic gastric cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Papillary cystadenoma lymphomatosum	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected109 at risk EG0020 affected111 at risk EG003
Renal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 21.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Renal oncocytoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 21.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Sarcoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected109 at risk EG0020 affected111 at risk EG003
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 21.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Cerebrovascular accident	Nervous system disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0021 affected111 at risk EG003
Sciatica	Nervous system disorders	MedDRA version 21.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Syncope	Nervous system disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected109 at risk EG0021 affected111 at risk EG003
Arachnoid cyst	Nervous system disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Brain stem infarction	Nervous system disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Carpal tunnel syndrom	Nervous system disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected109 at risk EG0020 affected111 at risk EG003
Cerebral ischaemia	Nervous system disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Chronic inflammatory demyelinating polyradiculoneuropathy	Nervous system disorders	MedDRA version 21.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Cubital tunnel syndrome	Nervous system disorders	MedDRA version 21.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Dizziness	Nervous system disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Haemorrhagic stroke	Nervous system disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected109 at risk EG0020 affected111 at risk EG003
Meningeal disorder	Nervous system disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Subarachnoid haemorrhage	Nervous system disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Transient ischaemic attack	Nervous system disorders	MedDRA version 21.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Trigeminal neuralgia	Nervous system disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected109 at risk EG0020 affected111 at risk EG003
Device dislocation	Product Issues	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Depression	Psychiatric disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected109 at risk EG0020 affected111 at risk EG003
Urinary retention	Renal and urinary disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected109 at risk EG0021 affected111 at risk EG003
Bladder neck obstruction	Renal and urinary disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0021 affected111 at risk EG003
Renal infarct	Renal and urinary disorders	MedDRA version 21.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Colpocele	Reproductive system and breast disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Uterine polyp	Reproductive system and breast disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Uterine prolapse	Reproductive system and breast disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Vulvar dysplasia	Reproductive system and breast disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0021 affected111 at risk EG003
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA version 21.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0021 affected111 at risk EG003
Pulmonary fibrosis	Respiratory, thoracic and mediastinal disorders	MedDRA version 21.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Sleep apnoea syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Panniculitis	Skin and subcutaneous tissue disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0021 affected111 at risk EG003
Removal of internal fixation	Surgical and medical procedures	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Hypertension	Vascular disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0022 affected111 at risk EG003
Aortic aneurysm	Vascular disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected109 at risk EG0020 affected111 at risk EG003
Aortic stenosis	Vascular disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Deep vein thrombosis	Vascular disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0021 affected111 at risk EG003
Peripheral artery thrombosis	Vascular disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected109 at risk EG0020 affected111 at risk EG003
Thrombosis	Vascular disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003
Varicose vein	Vascular disorders	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected109 at risk EG0020 affected111 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Hypothyroidism	Endocrine disorders	MedDRA version 21.1	Non-systematic Assessment	EG0002 affected107 at risk EG0011 affected109 at risk EG0021 affected111 at risk EG0036 affected111 at risk EG0042 affected109 at risk
Cataract	Eye disorders	MedDRA version 21.1	Non-systematic Assessment	EG0008 affected107 at risk EG0016 affected109 at risk EG00210 affected111 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA version 21.1	Non-systematic Assessment	EG0002 affected107 at risk EG0016 affected109 at risk EG0023 affected111 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA version 21.1	Non-systematic Assessment	EG0002 affected107 at risk EG0014 affected109 at risk EG0024 affected111 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA version 21.1	Non-systematic Assessment	EG0004 affected107 at risk EG0014 affected109 at risk EG0024 affected111 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA version 21.1	Non-systematic Assessment	EG0005 affected107 at risk EG0012 affected109 at risk EG0024 affected111 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA version 21.1	Non-systematic Assessment	EG0004 affected107 at risk EG0017 affected109 at risk EG0022 affected111 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA version 21.1	Non-systematic Assessment	EG0003 affected107 at risk EG0013 affected109 at risk EG0022 affected111 at risk EG003
Injection site pain	General disorders	MedDRA version 21.1	Non-systematic Assessment	EG0006 affected107 at risk EG0015 affected109 at risk EG00210 affected111 at risk EG003
Injection site bruising	General disorders	MedDRA version 21.1	Non-systematic Assessment	EG0004 affected107 at risk EG0015 affected109 at risk EG0026 affected111 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA version 21.1	Non-systematic Assessment	EG00021 affected107 at risk EG00125 affected109 at risk EG00228 affected111 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA version 21.1	Non-systematic Assessment	EG00027 affected107 at risk EG00125 affected109 at risk EG00220 affected111 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA version 21.1	Non-systematic Assessment	EG00010 affected107 at risk EG00113 affected109 at risk EG00210 affected111 at risk EG003
Influenza	Infections and infestations	MedDRA version 21.1	Non-systematic Assessment	EG00013 affected107 at risk EG00110 affected109 at risk EG00211 affected111 at risk EG003
Cystitis	Infections and infestations	MedDRA version 21.1	Non-systematic Assessment	EG0007 affected107 at risk EG00115 affected109 at risk EG0028 affected111 at risk EG003
Bronchitis	Infections and infestations	MedDRA version 21.1	Non-systematic Assessment	EG00010 affected107 at risk EG00111 affected109 at risk EG0026 affected111 at risk EG003
Pneumonia	Infections and infestations	MedDRA version 21.1	Non-systematic Assessment	EG0006 affected107 at risk EG0019 affected109 at risk EG0027 affected111 at risk EG003
Viral infection	Infections and infestations	MedDRA version 21.1	Non-systematic Assessment	EG0005 affected107 at risk EG0016 affected109 at risk EG0024 affected111 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA version 21.1	Non-systematic Assessment	EG0000 affected107 at risk EG0013 affected109 at risk EG0027 affected111 at risk EG003
Herpes zoster	Infections and infestations	MedDRA version 21.1	Non-systematic Assessment	EG0003 affected107 at risk EG0015 affected109 at risk EG0022 affected111 at risk EG003
Procedural pain	Injury, poisoning and procedural complications	MedDRA version 21.1	Non-systematic Assessment	EG00018 affected107 at risk EG0019 affected109 at risk EG0029 affected111 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA version 21.1	Non-systematic Assessment	EG0005 affected107 at risk EG0019 affected109 at risk EG0029 affected111 at risk EG003
Ligament sprain	Injury, poisoning and procedural complications	MedDRA version 21.1	Non-systematic Assessment	EG0006 affected107 at risk EG0015 affected109 at risk EG0026 affected111 at risk EG003
Skin abrasion	Injury, poisoning and procedural complications	MedDRA version 21.1	Non-systematic Assessment	EG0001 affected107 at risk EG0015 affected109 at risk EG0027 affected111 at risk EG003
C-reactive protein increased	Investigations	MedDRA version 21.1	Non-systematic Assessment	EG0003 affected107 at risk EG0012 affected109 at risk EG0020 affected111 at risk EG003
Hypercholesterolaemia	Metabolism and nutrition disorders	MedDRA version 21.1	Non-systematic Assessment	EG0004 affected107 at risk EG0015 affected109 at risk EG0023 affected111 at risk EG003
Hyperlipidaemia	Metabolism and nutrition disorders	MedDRA version 21.1	Non-systematic Assessment	EG0003 affected107 at risk EG0017 affected109 at risk EG0024 affected111 at risk EG003
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA version 21.1	Non-systematic Assessment	EG0003 affected107 at risk EG0016 affected109 at risk EG0023 affected111 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA version 21.1	Non-systematic Assessment	EG00058 affected107 at risk EG00159 affected109 at risk EG00257 affected111 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA version 21.1	Non-systematic Assessment	EG00024 affected107 at risk EG00128 affected109 at risk EG00229 affected111 at risk EG003
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA version 21.1	Non-systematic Assessment	EG00021 affected107 at risk EG00122 affected109 at risk EG00224 affected111 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA version 21.1	Non-systematic Assessment	EG00020 affected107 at risk EG00116 affected109 at risk EG00218 affected111 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA version 21.1	Non-systematic Assessment	EG00015 affected107 at risk EG00112 affected109 at risk EG00224 affected111 at risk EG003
Joint swelling	Musculoskeletal and connective tissue disorders	MedDRA version 21.1	Non-systematic Assessment	EG00010 affected107 at risk EG00114 affected109 at risk EG00211 affected111 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA version 21.1	Non-systematic Assessment	EG0007 affected107 at risk EG0014 affected109 at risk EG0029 affected111 at risk EG003
Spinal pain	Musculoskeletal and connective tissue disorders	MedDRA version 21.1	Non-systematic Assessment	EG0005 affected107 at risk EG0011 affected109 at risk EG0025 affected111 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA version 21.1	Non-systematic Assessment	EG0006 affected107 at risk EG0014 affected109 at risk EG0024 affected111 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA version 21.1	Non-systematic Assessment	EG0004 affected107 at risk EG0014 affected109 at risk EG0028 affected111 at risk EG003
Periarthritis	Musculoskeletal and connective tissue disorders	MedDRA version 21.1	Non-systematic Assessment	EG0003 affected107 at risk EG0018 affected109 at risk EG0025 affected111 at risk EG003
Plantar fasciitis	Musculoskeletal and connective tissue disorders	MedDRA version 21.1	Non-systematic Assessment	EG0003 affected107 at risk EG0016 affected109 at risk EG0027 affected111 at risk EG003
Tendonitis	Musculoskeletal and connective tissue disorders	MedDRA version 21.1	Non-systematic Assessment	EG0002 affected107 at risk EG0018 affected109 at risk EG0022 affected111 at risk EG003
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA version 21.1	Non-systematic Assessment	EG0002 affected107 at risk EG0014 affected109 at risk EG0022 affected111 at risk EG003
Headache	Nervous system disorders	MedDRA version 21.1	Non-systematic Assessment	EG00015 affected107 at risk EG00114 affected109 at risk EG00211 affected111 at risk EG003
Sciatica	Nervous system disorders	MedDRA version 21.1	Non-systematic Assessment	EG00011 affected107 at risk EG0018 affected109 at risk EG0024 affected111 at risk EG003
Dizziness	Nervous system disorders	MedDRA version 21.1	Non-systematic Assessment	EG0007 affected107 at risk EG0013 affected109 at risk EG0023 affected111 at risk EG003
Hypoaesthesia	Nervous system disorders	MedDRA version 21.1	Non-systematic Assessment	EG0007 affected107 at risk EG0014 affected109 at risk EG0025 affected111 at risk EG003
Memory impairment	Nervous system disorders	MedDRA version 21.1	Non-systematic Assessment	EG0004 affected107 at risk EG0010 affected109 at risk EG0026 affected111 at risk EG003
Insomnia	Psychiatric disorders	MedDRA version 21.1	Non-systematic Assessment	EG0003 affected107 at risk EG0010 affected109 at risk EG0027 affected111 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA version 21.1	Non-systematic Assessment	EG0009 affected107 at risk EG00112 affected109 at risk EG00212 affected111 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA version 21.1	Non-systematic Assessment	EG0007 affected107 at risk EG0011 affected109 at risk EG0021 affected111 at risk EG003
Hypertension	Vascular disorders	MedDRA version 21.1	Non-systematic Assessment	EG00017 affected107 at risk EG00124 affected109 at risk EG00214 affected111 at risk EG003

ID	Term
D010003	Osteoarthritis
D001168	Arthritis
D007592	Joint Diseases
D009140	Musculoskeletal Diseases
D012216	Rheumatic Diseases

ID	Title	Description
BG000	Placebo	Participants received Placebo matched to Sprifermin as intra-articular injection once every week for 3 consecutive weeks for 4 cycles, that is at week 0, 1, 2 in Cycle 1; at week 26, 27, 28 in Cycle 2; at week 52, 53, 54 in Cycle 3 and at week 78, 79, 80 in Cycle 4 at interval of 6 months.
BG001	Sprifermin (AS902330) 30 mcg/Placebo - 2 Cycles	Participants received Sprifermin 30 micrograms (mcg) as intra-articular injection once every week for 3 consecutive weeks for 2 alternative cycles, that is at week 0, 1, 2 in Cycle 1 and at week 52, 53, 54 in Cycle 3; and received placebo matched to Sprifermin once every week for 3 consecutive weeks for 2 alternative cycles, that is at week 26, 27, 28 in Cycle 2 and at week 78, 79, 80 in Cycle 4 at interval of 6 months.
BG002	Sprifermin (AS902330) 30 mcg- 4 Cycles	Participants received Sprifermin 30 micrograms (mcg) as intra-articular injection once every week for 3 consecutive weeks for 4 cycles, that is at week 0, 1, 2 in Cycle 1; at week 26, 27, 28 in Cycle 2; at week 52, 53, 54 in Cycle 3 and at week 78, 79, 80 in Cycle 4 at interval of 6 months.
BG003	Sprifermin (AS902330) 100 mcg/Placebo- 2 Cycles	Participants received Sprifermin 100 mcg as intra-articular injection once every week for 3 consecutive weeks for 2 alternative cycles, that is at week 0, 1, 2 in Cycle 1 and at week 52, 53, 54 in Cycle 3; and received placebo matched to Sprifermin once every week for 3 consecutive weeks for 2 alternative cycles, that is at week 26, 27, 28 in Cycle 2 and at week 78, 79, 80 in Cycle 4 at interval of 6 months.
BG004	Sprifermin (AS902330) 100 mcg- 4 Cycles	Participants received Sprifermin 100 mcg as intra-articular injection once every week for 3 consecutive weeks for 4 cycles, that is at week 0, 1, 2 in Cycle 1; at week 26, 27, 28 in Cycle 2; at week 52, 53, 54 in Cycle 3 and at week 78, 79, 80 in Cycle 4 at interval of 6 months.
BG005	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Participants received Placebo matched to Sprifermin as intra-articular injection once every week for 3 consecutive weeks for 4 cycles, that is at week 0, 1, 2 in Cycle 1; at week 26, 27, 28 in Cycle 2; at week 52, 53, 54 in Cycle 3 and at week 78, 79, 80 in Cycle 4 at interval of 6 months.	1	107	39	107	105	107
EG001	Sprifermin (AS902330) 30 mcg/Placebo - 2 Cycles	Participants received Sprifermin 30 micrograms (mcg) as intra-articular injection once every week for 3 consecutive weeks for 2 alternative cycles, that is at week 0, 1, 2 in Cycle 1 and at week 52, 53, 54 in Cycle 3; and received placebo matched to Sprifermin once every week for 3 consecutive weeks for 2 alternative cycles, that is at week 26, 27, 28 in Cycle 2 and at week 78, 79, 80 in Cycle 4 at interval of 6 months.	0	109	35	109	106	109
EG002	Sprifermin (AS902330) 30 mcg- 4 Cycles	Participants received Sprifermin 30 micrograms (mcg) as intra-articular injection once every week for 3 consecutive weeks for 4 cycles, that is at week 0, 1, 2 in Cycle 1; at week 26, 27, 28 in Cycle 2; at week 52, 53, 54 in Cycle 3 and at week 78, 79, 80 in Cycle 4 at interval of 6 months.	0	111	34	111	109	111
EG003	Sprifermin (AS902330) 100 mcg/Placebo (2 Cycles)	Participants received Sprifermin 100 mcg as intra-articular injection once every week for 3 consecutive weeks for 2 alternative cycles, that is at week 0, 1, 2 in Cycle 1 and at week 52, 53, 54 in Cycle 3; and received placebo matched to Sprifermin once every week for 3 consecutive weeks for 2 alternative cycles, that is at week 26, 27, 28 in Cycle 2 and at week 78, 79, 80 in Cycle 4 at interval of 6 months.	0	111	32	111	106	111
EG004	Sprifermin (AS902330) 100 mcg- 4 Cycles	Participants received Sprifermin 100 mcg as intra-articular injection once every week for 3 consecutive weeks for 4 cycles, that is at week 0, 1, 2 in Cycle 1; at week 26, 27, 28 in Cycle 2; at week 52, 53, 54 in Cycle 3 and at week 78, 79, 80 in Cycle 4 at interval of 6 months.	0	109	41	109	107	109