A Phase 1/2 Study of an Investigational Drug, ALN-CC5, in... | NCT02352493

Label	Type	Description	Intervention Names
ALN-CC5	Active Comparator		Drug: ALN-CC5
Sterile Normal Saline (0.9% NaCl)	Placebo Comparator		Drug: Sterile Normal Saline (0.9% NaCl)

Name	Type	Description	Arm Group Labels	Other Names
ALN-CC5	Drug	Single or multiple doses of ALN-CC5 by subcutaneous (sc) injection	ALN-CC5

Measure	Description	Time Frame
Number of Participants With Adverse Events	Adverse events were reported for single-ascending doses (SAD) or multiple ascending doses (MAD) of ALN-CC5 when administered to healthy adult subjects and of multiple doses (MD) in patients with paroxysmal nocturnal hemoglobinuria (PNH)	Part A: through day 658; Part B: through day 532; Part C: through day 280

Measure	Description	Time Frame
Pharmacodynamic (PD) Effect of ALN-CC5: Percentage Reduction From Baseline in Complement Alternative Pathway (CAP)	Complement activity was measured in serum samples collected at timepoints throughout the study using the CAP ELISA assay. Percentage reduction was calculated relative to baseline levels. A positive value indicates a reduction in CAP from baseline.	Part A: through day 70; Part B: through day 140; Part C: through day 140

Name	Affiliation	Role
Nader Najafian, MD	Alnylam Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Clinical Trial Site		Barcelona			Spain
Clinical Trial Site

PubMed Identifier	Type	Citation	Retractions
35749284	Derived	Ishigooka H, Katsumata H, Saiga K, Tokita D, Motoi S, Matsui C, Suzuki Y, Tomimatsu A, Nakatani T, Kuboi Y, Yamakawa T, Ikeda T, Ishii R, Imai T, Takagi T, Tanabe K. Novel Complement C5 Small-interfering RNA Lipid Nanoparticle Prolongs Graft Survival in a Hypersensitized Rat Kidney Transplant Model. Transplantation. 2022 Dec 1;106(12):2338-2347. doi: 10.1097/TP.0000000000004207. Epub 2022 Nov 22.
33047216

ID	Title	Description
FG000	Placebo - Single Ascending Dose	Healthy volunteers received a single dose of placebo (normal saline)
FG001	ALN-CC5 50mg - Single Ascending Dose	Healthy volunteers received a single dose of ALN-CC5 50mg

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
SAP	No	Yes	No	Statistical Analysis Plan	Nov 18, 2016	Jul 30, 2018

Arm/Group Information

ID	Title	Description
BG000	Placebo - Single Ascending Dose	Healthy volunteers received a single dose of placebo (normal saline)
BG001	ALN-CC5 50mg - Single Ascending Dose	Healthy volunteers received a single dose of ALN-CC5 50mg
BG002	ALN-CC5 50mg (Japanese) - Single Ascending Dose	Japanese healthy volunteers received a single dose of ALN-CC5 50mg
BG003	ALN-CC5 200mg - Single Ascending Dose	Healthy volunteers received a single dose of ALN-CC5 200mg
BG004	ALN-CC5 200mg (Japanese) - Single Ascending Dose	Japanese healthy volunteers received a single dose of ALN-CC5 200mg
BG005	ALN-CC5 400mg - Single Ascending Dose	Healthy volunteers received a single dose of ALN-CC5 400mg
BG006	ALN-CC5 600mg - Single Ascending Dose	Healthy volunteers received a single dose of ALN-CC5 600mg
BG007	ALN-CC5 600mg (Japanese) - Single Ascending Dose	Japanese healthy volunteers received a single dose of ALN-CC5 600mg
BG008	ALN-CC5 900mg - Single Ascending Dose	Healthy volunteers received a single dose of ALN-CC5 900mg
BG009	Placebo - Multiple Ascending Dose	Healthy volunteers received multiple doses of placebo (normal saline) per corresponding active drug regimen
BG010	ALN-CC5 100mg Weekly - Multiple Ascending Dose	Healthy volunteers received weekly doses of ALN-CC5 100mg for 5 doses
BG011	ALN-CC5 200mg Weekly - Multiple Ascending Dose	Healthy volunteers received weekly doses of ALN-CC5 200mg for 5 doses
BG012	ALN-CC5 400mg Weekly - Multiple Ascending Dose	Healthy volunteers received weekly doses of ALN-CC5 400mg for 5 doses
BG013	ALN-CC5 600mg Biweekly - Multiple Ascending Dose	Healthy volunteers received biweekly doses of ALN-CC5 600mg for 7 doses
BG014	ALN-CC5 200mg Weekly/Biweekly - Multiple Ascending Dose	Healthy volunteers received weekly doses of ALN-CC5 200mg for 5 doses followed by biweekly doses of 200mg for 4 doses
BG015	ALN-CC5 200mg Weekly/Monthly - Multiple Ascending Dose	Healthy volunteers received weekly doses of ALN-CC5 200mg for 5 doses followed by monthly doses of 200mg for 2 doses
BG016	ALN-CC5 Multiple Dose - Eculizumab Treated	Patients received weekly doses of ALN-CC5 200mg or ALN-CC5 400mg for up to 12 weeks concomitantly with eculizumab
BG017	ALN-CC5 Multiple Dose - Eculizumab Naive	Patients naive to eculizumab received weekly doses of ALN-CC5 400mg for 8 doses or ALN-CC5 200mg for 13 doses followed by weekly doses of ALN-CC5 400mg for 4 doses
BG018	Total	Total of all reporting groups

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

Number of Participants With Adverse Events

Adverse events were reported for single-ascending doses (SAD) or multiple ascending doses (MAD) of ALN-CC5 when administered to healthy adult subjects and of multiple doses (MD) in patients with paroxysmal nocturnal hemoglobinuria (PNH)

Posted

Count of Participants

Participants

Part A: through day 658; Part B: through day 532; Part C: through day 280

ID	Title	Description
OG000	Placebo - Single Ascending Dose	Healthy volunteers received a single dose of placebo (normal saline)
OG001	ALN-CC5 50mg - Single Ascending Dose	Healthy volunteers received a single dose of ALN-CC5 50mg
OG002	ALN-CC5 50mg (Japanese) - Single Ascending Dose	Japanese healthy volunteers received a single dose of ALN-CC5 50mg
OG003	ALN-CC5 200mg - Single Ascending Dose	Healthy volunteers received a single dose of ALN-CC5 200mg
OG004	ALN-CC5 200mg (Japanese) - Single Ascending Dose	Japanese healthy volunteers received a single dose of ALN-CC5 200mg
OG005	ALN-CC5 400mg - Single Ascending Dose	Healthy volunteers received a single dose of ALN-CC5 400mg
OG006	ALN-CC5 600mg - Single Ascending Dose	Healthy volunteers received a single dose of ALN-CC5 600mg
OG007	ALN-CC5 600mg (Japanese) - Single Ascending Dose	Japanese healthy volunteers received a single dose of ALN-CC5 600mg
OG008	ALN-CC5 900mg - Single Ascending Dose	Healthy volunteers received a single dose of ALN-CC5 900mg
OG009	Placebo - Multiple Ascending Dose	Healthy volunteers received multiple doses of placebo (normal saline) per corresponding active drug regimen
OG010	ALN-CC5 100mg Weekly - Multiple Ascending Dose	Healthy volunteers received weekly doses of ALN-CC5 100mg for 5 doses
OG011	ALN-CC5 200mg Weekly - Multiple Ascending Dose	Healthy volunteers received weekly doses of ALN-CC5 200mg for 5 doses
OG012	ALN-CC5 400mg Weekly - Multiple Ascending Dose	Healthy volunteers received weekly doses of ALN-CC5 400mg for 5 doses
OG013	ALN-CC5 600mg Biweekly - Multiple Ascending Dose	Healthy volunteers received biweekly doses of ALN-CC5 600mg for 7 doses
OG014	ALN-CC5 200mg Weekly/Biweekly - Multiple Ascending Dose	Healthy volunteers received weekly doses of ALN-CC5 200mg for 5 doses followed by biweekly doses of 200mg for 4 doses
OG015	ALN-CC5 200mg Weekly/Monthly - Multiple Ascending Dose	Healthy volunteers received weekly doses of ALN-CC5 200mg for 5 doses followed by monthly doses of 200mg for 2 doses
OG016	ALN-CC5 Multiple Dose - Eculizumab Treated	Patients received weekly doses of ALN-CC5 200mg or ALN-CC5 400mg for up to 12 weeks concomitantly with eculizumab
OG017	ALN-CC5 Multiple Dose - Eculizumab Naive	Patients naive to eculizumab received weekly doses of ALN-CC5 400mg for 8 doses or weekly doses of ALN-CC5 200mg for 13 doses followed by weekly doses of ALN-CC5 400mg for 4 doses

Units	Counts
Participants	OG0008 OG0013 OG0023 OG003

Title

Denominators

Categories

At least 1 Treatment Emergent Adverse Event (TEAE)

Title	Measurements
	OG0006 OG0010 OG0023 OG003

Secondary

Pharmacodynamic (PD) Effect of ALN-CC5: Percentage Reduction From Baseline in Complement Alternative Pathway (CAP)

Complement activity was measured in serum samples collected at timepoints throughout the study using the CAP ELISA assay. Percentage reduction was calculated relative to baseline levels. A positive value indicates a reduction in CAP from baseline.

Posted

Mean

Standard Error

percentage reduction

Part A: through day 70; Part B: through day 140; Part C: through day 140

ID	Title	Description
OG000	Placebo - Single Ascending Dose	Healthy volunteers received a single dose of placebo (normal saline)
OG001	ALN-CC5 50mg - Single Ascending Dose	Healthy volunteers received a single dose of ALN-CC5 50mg
OG002	ALN-CC5 50mg (Japanese) - Single Ascending Dose	Japanese healthy volunteers received a single dose of ALN-CC5 50mg
OG003	ALN-CC5 200mg - Single Ascending Dose	Healthy volunteers received a single dose of ALN-CC5 200mg

Secondary

Pharmacodynamic (PD) Effect of ALN-CC5: Percentage Reduction From Baseline in Complement Classical Pathway (CCP)

Complement activity was measured in serum samples collected at time points throughout the study using the CCP ELISA assay. Percentage reduction was calculated relative to baseline levels. A positive value indicates a reduction in CCP from baseline.

Posted

Mean

Standard Error

percentage reduction

Part A: through day 70; Part B: through day 140; Part C: through day 140

ID	Title	Description
OG000	Placebo - Single Ascending Dose	Healthy volunteers received a single dose of placebo (normal saline)
OG001	ALN-CC5 50mg - Single Ascending Dose	Healthy volunteers received a single dose of ALN-CC5 50mg
OG002	ALN-CC5 50mg (Japanese) - Single Ascending Dose	Japanese healthy volunteers received a single dose of ALN-CC5 50mg
OG003	ALN-CC5 200mg - Single Ascending Dose	Healthy volunteers received a single dose of ALN-CC5 200mg

Secondary

Pharmacodynamic (PD) Effect of ALN-CC5: Percentage Reduction From Baseline in C5 Protein Levels

Total C5 protein levels were measured in serum samples collected at time points throughout the study using a mass spectrometry-based method. Percentage reduction was calculated relative to baseline levels. A positive value indicates a reduction in C5 protein level from baseline.

Posted

Mean

Standard Error

percentage reduction

Part A: through day 70; Part B: through day 140; Part C: through day 140

ID	Title	Description
OG000	Placebo - Single Ascending Dose	Healthy volunteers received a single dose of placebo (normal saline)
OG001	ALN-CC5 50mg - Single Ascending Dose	Healthy volunteers received a single dose of ALN-CC5 50mg
OG002	ALN-CC5 50mg (Japanese) - Single Ascending Dose	Japanese healthy volunteers received a single dose of ALN-CC5 50mg
OG003	ALN-CC5 200mg - Single Ascending Dose	Healthy volunteers received a single dose of ALN-CC5 200mg

Secondary

Pharmacokinetic (PK) Effect of ALN-CC5: Cmax (25-mer)

Maximum observed plasma concentration (Cmax) of ALN-CC5 (cemdisiran) 25-mer.

All healthy volunteers/patients who received at least one dose of study drug, and who had evaluable plasma or urine PK concentration. For the ALN-CC5 Multiple Dose - Eculizumab Naive group, Day 84 plasma samples were not collected.

Posted

Mean

Standard Deviation

ng/mL

Part A: 0-48 hrs, Day 0; Part B (weekly dosing cohorts): 0-48 hrs, Day 28; Part B (biweekly, weekly/monthly/biweekly/monthly cohorts): 0-48 hrs, Day 84; Part C: 0- 24 hrs, Day 84

ID	Title	Description
OG000	ALN-CC5 50mg - Single Ascending Dose	Healthy volunteers received a single dose of ALN-CC5 50mg
OG001	ALN-CC5 50mg (Japanese) - Single Ascending Dose	Japanese healthy volunteers received a single dose of ALN-CC5 50mg
OG002	ALN-CC5 200mg - Single Ascending Dose	Healthy volunteers received a single dose of ALN-CC5 200mg
OG003	ALN-CC5 200mg (Japanese) - Single Ascending Dose

Secondary

Pharmacokinetic (PK) Effect of ALN-CC5: Cmax (23-mer)

Maximum observed plasma concentration (Cmax) of ALN-CC5 (cemdisiran) 23-mer.

Posted

Mean

Standard Deviation

ng/mL

Part A: 0-48 hrs, Day 0; Part B (weekly dosing cohorts): 0-48 hrs, Day 28; Part B (biweekly, weekly/monthly/biweekly/monthly cohorts): 0-48 hrs, Day 84; Part C: 0- 24 hrs, Day 84

ID	Title	Description
OG000	ALN-CC5 50mg - Single Ascending Dose	Healthy volunteers received a single dose of ALN-CC5 50mg
OG001	ALN-CC5 50mg (Japanese) - Single Ascending Dose	Japanese healthy volunteers received a single dose of ALN-CC5 50mg
OG002	ALN-CC5 200mg - Single Ascending Dose	Healthy volunteers received a single dose of ALN-CC5 200mg
OG003	ALN-CC5 200mg (Japanese) - Single Ascending Dose

Secondary

Pharmacokinetic (PK) Effect of ALN-CC5: T Max (25-mer)

Time of maximum observed plasma concentration (T max) of ALN-CC5 (cemdisiran) 25-mer.

Posted

Median

Full Range

Part A: 0-48 hrs, Day 0; Part B (weekly dosing cohorts): 0-48 hrs, Day 28; Part B (biweekly, weekly/monthly/biweekly/monthly cohorts): 0-48 hrs, Day 84; Part C: 0- 24 hrs, Day 84

ID	Title	Description
OG000	ALN-CC5 50mg - Single Ascending Dose	Healthy volunteers received a single dose of ALN-CC5 50mg
OG001	ALN-CC5 50mg (Japanese) - Single Ascending Dose	Japanese healthy volunteers received a single dose of ALN-CC5 50mg
OG002	ALN-CC5 200mg - Single Ascending Dose	Healthy volunteers received a single dose of ALN-CC5 200mg
OG003	ALN-CC5 200mg (Japanese) - Single Ascending Dose

Secondary

Pharmacokinetic (PK) Effect of ALN-CC5: T Max (23-mer)

Time of maximum observed plasma concentration (T max) of ALN-CC5 (cemdisiran) 23-mer.

Posted

Median

Full Range

Part A: 0-48 hrs, Day 0; Part B (weekly dosing cohorts): 0-48 hrs, Day 28; Part B (biweekly, weekly/monthly/biweekly/monthly cohorts): 0-48 hrs, Day 84; Part C: 0- 24 hrs, Day 84

ID	Title	Description
OG000	ALN-CC5 50mg - Single Ascending Dose	Healthy volunteers received a single dose of ALN-CC5 50mg
OG001	ALN-CC5 50mg (Japanese) - Single Ascending Dose	Japanese healthy volunteers received a single dose of ALN-CC5 50mg
OG002	ALN-CC5 200mg - Single Ascending Dose	Healthy volunteers received a single dose of ALN-CC5 200mg
OG003	ALN-CC5 200mg (Japanese) - Single Ascending Dose

Secondary

Pharmacokinetic (PK) Effect of ALN-CC5: AUC 0-t (25-mer)

Area under the plasma concentration-time curve over the dosing interval zero to time (AUC 0-t) of ALN-CC5 (cemdisiran) 25-mer.

Posted

Mean

Standard Deviation

h*ng/mL

Part A: 0-48 hrs, Day 0; Part B (weekly dosing cohorts): 0-48 hrs, Day 28; Part B (biweekly, weekly/monthly/biweekly/monthly cohorts): 0-48 hrs, Day 84; Part C: 0- 24 hrs, Day 84

ID	Title	Description
OG000	ALN-CC5 50mg - Single Ascending Dose	Healthy volunteers received a single dose of ALN-CC5 50mg
OG001	ALN-CC5 50mg (Japanese) - Single Ascending Dose	Japanese healthy volunteers received a single dose of ALN-CC5 50mg
OG002	ALN-CC5 200mg - Single Ascending Dose	Healthy volunteers received a single dose of ALN-CC5 200mg
OG003	ALN-CC5 200mg (Japanese) - Single Ascending Dose

Secondary

Pharmacokinetic (PK) Effect of ALN-CC5: AUC 0-t (23-mer)

Area under the plasma concentration-time curve over the dosing interval zero to time (AUC 0-t) of ALN-CC5 (cemdisiran) 23-mer.

Posted

Mean

Standard Deviation

h*ng/mL

Part A: 0-48 hrs, Day 0; Part B (weekly dosing cohorts): 0-48 hrs, Day 28; Part B (biweekly, weekly/monthly/biweekly/monthly cohorts): 0-48 hrs, Day 84; Part C: 0- 24 hrs, Day 84

ID	Title	Description
OG000	ALN-CC5 50mg - Single Ascending Dose	Healthy volunteers received a single dose of ALN-CC5 50mg
OG001	ALN-CC5 50mg (Japanese) - Single Ascending Dose	Japanese healthy volunteers received a single dose of ALN-CC5 50mg
OG002	ALN-CC5 200mg - Single Ascending Dose	Healthy volunteers received a single dose of ALN-CC5 200mg
OG003	ALN-CC5 200mg (Japanese) - Single Ascending Dose

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo - Single Ascending Dose	Healthy volunteers received a single dose of placebo (normal saline)	8	8	6	8
EG001	ALN-CC5 50mg - Single Ascending Dose	Healthy volunteers received a single dose of ALN-CC5 50mg	3	3	0	3
EG002	ALN-CC5 50mg (Japanese) - Single Ascending Dose	Japanese healthy volunteers received a single dose of ALN-CC5 50mg	3	3	3	3
EG003	ALN-CC5 200mg - Single Ascending Dose	Healthy volunteers received a single dose of ALN-CC5 200mg	3	3	2	3
EG004	ALN-CC5 200mg (Japanese) - Single Ascending Dose	Japanese healthy volunteers received a single dose of ALN-CC5 200mg	3	3	2	3
EG005	ALN-CC5 400mg - Single Ascending Dose	Healthy volunteers received a single dose of ALN-CC5 400mg	3	3	3	3
EG006	ALN-CC5 600mg - Single Ascending Dose	Healthy volunteers received a single dose of ALN-CC5 600mg	3	3	3	3
EG007	ALN-CC5 600mg (Japanese) - Single Ascending Dose	Japanese healthy volunteers received a single dose of ALN-CC5 600mg	3	3	2	3
EG008	ALN-CC5 900mg - Single Ascending Dose	Healthy volunteers received a single dose of ALN-CC5 900mg	3	3	3	3
EG009	Placebo - Multiple Ascending Dose	Healthy volunteers received multiple doses of placebo (normal saline) per corresponding active drug regimen	6	6	6	6
EG010	ALN-CC5 100mg Weekly - Multiple Ascending Dose	Healthy volunteers received weekly doses of ALN-CC5 100mg for 5 doses	3	3	2	3
EG011	ALN-CC5 200mg Weekly - Multiple Ascending Dose	Healthy volunteers received weekly doses of ALN-CC5 200mg for 5 doses	3	3	3	3
EG012	ALN-CC5 400mg Weekly - Multiple Ascending Dose	Healthy volunteers received weekly doses of ALN-CC5 400mg for 5 doses	3	3	3	3
EG013	ALN-CC5 600mg Biweekly - Multiple Ascending Dose	Healthy volunteers received biweekly doses of ALN-CC5 600mg for 7 doses	3	3	3	3
EG014	ALN-CC5 200mg Weekly/Biweekly - Multiple Ascending Dose	Healthy volunteers received weekly doses of ALN-CC5 200mg for 5 doses followed by biweekly doses of 200mg for 4 doses	3	3	2	3
EG015	ALN-CC5 200mg Weekly/Monthly - Multiple Ascending Dose	Healthy volunteers received weekly doses of ALN-CC5 200mg for 5 doses followed by monthly doses of 200mg for 2 doses	3	3	3	3
EG016	ALN-CC5 Multiple Dose - Eculizumab Treated	Patients received weekly doses of ALN-CC5 200mg or ALN-CC5 400mg for up to 12 weeks concomitantly with eculizumab	3	3	3	3
EG017	ALN-CC5 Multiple Dose - Eculizumab Naive	Patients naive to eculizumab received weekly doses of ALN-CC5 400mg for 8 doses or weekly doses of ALN-CC5 200mg for 13 doses followed by weekly doses of ALN-CC5 400mg for 4 doses	3	3	3	3

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Fibroadenoma of breast	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG0030 affected3 at risk EG004
Influenza like illness	General disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0021 affected3 at risk EG003
Injection site pain	General disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Injection site rash	General disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Injection site oedema	General disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Chest discomfort	General disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Fatigue	General disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Injection site bruising	General disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Injection site erythema	General disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Injection site pruritus	General disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Injection site discomfort	General disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Pyrexia	General disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Anxiety	Psychiatric disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Insomnia	Psychiatric disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Tendon injury	Injury, poisoning and procedural complications	MedDRA (17.1)	Systematic Assessment	EG0001 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Sunburn	Injury, poisoning and procedural complications	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Weight decreased	Investigations	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Amylase increased	Investigations	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Transaminases increased	Investigations	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Haemolysis	Blood and lymphatic system disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Headache	Nervous system disorders	MedDRA (17.1)	Systematic Assessment	EG0001 affected8 at risk EG0010 affected3 at risk EG0021 affected3 at risk EG003
Somnolence	Nervous system disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0021 affected3 at risk EG003
Migraine	Nervous system disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
VIIth nerve paralysis	Nervous system disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Eye pruritus	Eye disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Vertigo	Ear and labyrinth disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0002 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0003 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Cheilitis	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0001 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Aphthous stomatitis	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Abdominal discomfort	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Choluria	Renal and urinary disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Rash pruritic	Skin and subcutaneous tissue disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Drug eruption	Skin and subcutaneous tissue disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (17.1)	Systematic Assessment	EG0001 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0003 affected8 at risk EG0010 affected3 at risk EG0022 affected3 at risk EG003
Vulvovaginal candidiasis	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0021 affected3 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Influenza	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Lower respiratory tract infection	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Pharyngitis	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Sensory disturbance	Nervous system disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Vessel puncture site pain	General disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0021 affected3 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0021 affected3 at risk EG003
Eye discharge	Eye disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Eye swelling	Eye disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Vision blurred	Eye disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Throat irritation	Respiratory, thoracic and mediastinal disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Ligament sprain	Injury, poisoning and procedural complications	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Head injury	Injury, poisoning and procedural complications	MedDRA (17.1)	Systematic Assessment	EG0001 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Seasonal allergy	Immune system disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003
Dizziness	Nervous system disorders	MedDRA (17.1)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected3 at risk EG0020 affected3 at risk EG003

ID	Term
D000743	Anemia, Hemolytic
D000740	Anemia
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D009190	Myelodysplastic Syndromes
D001855	Bone Marrow Diseases