Copper Concentration & Histopathologic Changes in Liver B... | NCT04422431

ID	Type	Description	Link
2019-003711-60	EudraCT Number

Label	Type	Description	Intervention Names
ALXN1840	Experimental	Participants will receive ALXN1840.	Drug: Bis-Choline Tetrathiomolybdate

Name	Type	Description	Arm Group Labels	Other Names
Bis-Choline Tetrathiomolybdate	Drug	Participants will be initiated at 15 milligrams once daily, then the dose will be increased to 30 milligrams once daily at Week 6.	ALXN1840

Measure	Description	Time Frame
Change From Baseline in Liver Cu Concentration at Week 48 (Treatment Period)	Liver biopsy samples were taken for the assessment of liver Cu concentration. Multiple imputation was used to impute missing data at Week 48 due to any reason based on Baseline values.	Baseline, Week 48 (Treatment Period)

Measure	Description	Time Frame
Number of Participants With Change From Baseline in Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Fibrosis Stage at Week 48 (Treatment Period)	Fibrosis from histology was evaluated by NASH CRN Fibrosis Stage, which was scaled from 0 to 4 stages where Score 0: None; Score 1: Perisinusoidal or periportal - 1a - mild, zone 3, perisinusoidal; Score 1: Perisinusoidal or periportal - 1b - moderate, zone 3, perisinusoidal; Score 1: Perisinusoidal or periportal - 1c - portal/periportal; Score 2: Both perisinusoidal and portal/periportal; Score 3: Bridging fibrosis; and Score 4: Cirrhosis. Higher scores indicated greater fibrosis.

Name	Affiliation	Role
Eugene S. Swenson, MD, PhD	Alexion Pharmaceuticals, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Sacramento	California	95817	United States
Research Site

Label	URL
Related Info	View source

ID	Title	Description
FG000	ALXN1840	Participants received ALXN1840 orally in the 48-week Treatment Period. Participants who completed the 48-week Treatment Period and agreed to enter a 48-week Extension Period, continued to receive ALXN1840. Participants who did not enter the Extension Period discontinued dosing at Week 48, and had a final study visit for safety follow-up at Week 52.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	May 27, 2022	May 18, 2023

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 Liver Cu Concentration at Week 48 (Treatment Period)

Liver biopsy samples were taken for the assessment of liver Cu concentration. Multiple imputation was used to impute missing data at Week 48 due to any reason based on Baseline values.

The Full Analysis Set in the Treatment Period included all participants who received at least 1 dose of study drug in the Treatment Period and had at least a Baseline liver Cu value evaluable.

Posted

Mean

Standard Error

μg/g

Baseline, Week 48 (Treatment Period)

ID	Title	Description
OG000	ALXN1840	Participants received ALXN1840 orally in the 48-week Treatment Period. Participants who completed the 48-week Treatment Period and agreed to enter a 48-week Extension Period, continued to receive ALXN1840. Participants who did not enter the Extension Period discontinued dosing at Week 48, and had a final study visit for safety follow-up at Week 52.

Units	Counts
Participants	OG00029

Title

Denominators

Categories

Title	Measurements
	OG00092.8± 56.34

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		t-test, 2 sided		0.1002														Other

Secondary

Number of Participants With Change From Baseline in Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Fibrosis Stage at Week 48 (Treatment Period)

Fibrosis from histology was evaluated by NASH CRN Fibrosis Stage, which was scaled from 0 to 4 stages where Score 0: None; Score 1: Perisinusoidal or periportal - 1a - mild, zone 3, perisinusoidal; Score 1: Perisinusoidal or periportal - 1b - moderate, zone 3, perisinusoidal; Score 1: Perisinusoidal or periportal - 1c - portal/periportal; Score 2: Both perisinusoidal and portal/periportal; Score 3: Bridging fibrosis; and Score 4: Cirrhosis. Higher scores indicated greater fibrosis.

The Full Analysis Set in the Treatment Period included all participants who received at least 1 dose of study drug in the Treatment Period and had at least a Baseline liver Cu value evaluable. 'Number analyzed' signifies participants evaluable at specified timepoint.

Posted

Count of Participants

Participants

Baseline, Week 48 (Treatment Period)

ID	Title	Description
OG000	ALXN1840	Participants received ALXN1840 orally in the 48-week Treatment Period. Participants who completed the 48-week Treatment Period and agreed to enter a 48-week Extension Period, continued to receive ALXN1840. Participants who did not enter the Extension Period discontinued dosing at Week 48, and had a final study visit for safety follow-up at Week 52.

Units	Counts

Secondary

Number of Participants With Change From Baseline in Metavir Fibrosis Score at Week 48 (Treatment Period)

Fibrosis from histology was evaluated by Metavir Fibrosis Score, which was ranged from 0 to 4 where Score 0: No fibrosis; Score 1: Stellate enlargement of portal tract but without septa formation; Score 2: Enlargement of portal tract with rare septa formation; Score 3: Numerous septa without cirrhosis; and Score 4: Cirrhosis. Higher scores indicated greater fibrosis.

Posted

Count of Participants

Participants

Baseline, Week 48 (Treatment Period)

ID	Title	Description
OG000	ALXN1840	Participants received ALXN1840 orally in the 48-week Treatment Period. Participants who completed the 48-week Treatment Period and agreed to enter a 48-week Extension Period, continued to receive ALXN1840. Participants who did not enter the Extension Period discontinued dosing at Week 48, and had a final study visit for safety follow-up at Week 52.

Units	Counts
Participants

Secondary

Number of Participants With Change From Baseline in Ishak Fibrosis Score at Week 48 (Treatment Period)

Fibrosis from histology was evaluated by Ishak Fibrosis Score, which was ranged from 0 to 6 where Score 0: No fibrosis; Score 1: Fibrous expansion of some portal areas, with or without short fibrous septa; Score 2: Fibrous expansion of most portal areas, with or without short fibrous septa; Score 3: Fibrous expansion of most portal areas with occasional portal to portal (P-P) bridging; and Score 4: Fibrous expansion of portal areas with marked bridging (P-P) as well as portal central (P-C); Score 5: Marked bridging (P-P and/or P-C) with occasional nodules (incomplete cirrhosis); and Score 6: Cirrhosis, probable or definite. Higher scores indicated greater fibrosis.

Posted

Count of Participants

Participants

Baseline, Week 48 (Treatment Period)

ID	Title	Description
OG000	ALXN1840	Participants received ALXN1840 orally in the 48-week Treatment Period. Participants who completed the 48-week Treatment Period and agreed to enter a 48-week Extension Period, continued to receive ALXN1840. Participants who did not enter the Extension Period discontinued dosing at Week 48, and had a final study visit for safety follow-up at Week 52.

Secondary

Change From Baseline in Hepatic Collagen Content at Week 48 (Treatment Period)

Fibrosis from histology was evaluated by morphometric quantification of hepatic collagen content.

The Full Analysis Set in the Treatment Period included all participants who received at least 1 dose of study drug in the Treatment Period and had at least a Baseline liver Cu value evaluable. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Posted

Mean

Standard Deviation

percentage of collagen

Baseline, Week 48 (Treatment Period)

ID	Title	Description
OG000	ALXN1840	Participants received ALXN1840 orally in the 48-week Treatment Period. Participants who completed the 48-week Treatment Period and agreed to enter a 48-week Extension Period, continued to receive ALXN1840. Participants who did not enter the Extension Period discontinued dosing at Week 48, and had a final study visit for safety follow-up at Week 52.

Units	Counts
Participants	OG000

Secondary

Change From Baseline in a-SMA Content at Week 48 (Treatment Period)

Fibrosis from histology was evaluated by morphometric quantification of hepatic a-SMA content.

The Full Analysis Set in the Treatment Period included all participants who received at least 1 dose of study drug in the Treatment Period and had at least a Baseline liver Cu value evaluable. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Posted

Mean

Standard Deviation

percentage of a-SMA

Baseline, Week 48 (Treatment Period)

ID	Title	Description
OG000	ALXN1840	Participants received ALXN1840 orally in the 48-week Treatment Period. Participants who completed the 48-week Treatment Period and agreed to enter a 48-week Extension Period, continued to receive ALXN1840. Participants who did not enter the Extension Period discontinued dosing at Week 48, and had a final study visit for safety follow-up at Week 52.

Units	Counts
Participants	OG000

Secondary

Number of Participants With Change From Baseline in NAS Steatosis Grading Score at Week 48 (Treatment Period)

Steatosis from histology was evaluated by the steatosis component of the NAS, which was ranged from 0 to 3 where Score 0: < 5% (minimal); Score 1: 5 - 33% (mild); Score 2: 34 - 66% (moderate); and Score 3: > 66% (severe). Higher scores indicated greater steatosis.

Posted

Count of Participants

Participants

Baseline, Week 48 (Treatment Period)

ID	Title	Description
OG000	ALXN1840	Participants received ALXN1840 orally in the 48-week Treatment Period. Participants who completed the 48-week Treatment Period and agreed to enter a 48-week Extension Period, continued to receive ALXN1840. Participants who did not enter the Extension Period discontinued dosing at Week 48, and had a final study visit for safety follow-up at Week 52.

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Hepatic Fat Content at Week 48 (Treatment Period)

Steatosis from histology was evaluated by morphometric quantification of hepatic fat content.

The Full Analysis Set in the Treatment Period included all participants who received at least 1 dose of study drug in the Treatment Period and had at least a Baseline liver Cu value evaluable. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Posted

Mean

Standard Deviation

percentage of fat

Baseline, Week 48 (Treatment Period)

ID	Title	Description
OG000	ALXN1840	Participants received ALXN1840 orally in the 48-week Treatment Period. Participants who completed the 48-week Treatment Period and agreed to enter a 48-week Extension Period, continued to receive ALXN1840. Participants who did not enter the Extension Period discontinued dosing at Week 48, and had a final study visit for safety follow-up at Week 52.

Units	Counts
Participants	OG000

Secondary

Change From Baseline in NAS Total Score at Week 48 (Treatment Period)

Inflammation was quantified by the NAS total score. The score is defined as the unweighted sum of the scores for steatosis (0 [minimal] to 3 [severe]), lobular inflammation (0 [none] to 3 [>4 foci / 200x field]), and hepatocellular ballooning (0 [none] to 2 [many]), thus ranging from 0 (no inflammation) to 8 (severe inflammation), with higher scores indicating more severe disease.

The Full Analysis Set in the Treatment Period included all participants who received at least 1 dose of study drug in the Treatment Period and had at least a Baseline liver Cu value evaluable. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Posted

Mean

Standard Deviation

units on a scale

Baseline, Week 48 (Treatment Period)

ID	Title	Description
OG000	ALXN1840	Participants received ALXN1840 orally in the 48-week Treatment Period. Participants who completed the 48-week Treatment Period and agreed to enter a 48-week Extension Period, continued to receive ALXN1840. Participants who did not enter the Extension Period discontinued dosing at Week 48, and had a final study visit for safety follow-up at Week 52.

Units	Counts
Participants

Secondary

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

An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An SAE was an AE that met at least 1 of the following criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization for the AE, persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug), important medical event or reaction. The TEAEs were AEs with onset on or after the first study drug dose. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.

Safety Analysis Set in the Treatment Period included all participants who received at least 1 dose of treatment in the Treatment Period.

Posted

Count of Participants

Participants

Day 1 (Treatment Period) up to Week 48 (Treatment Period)

ID	Title	Description
OG000	ALXN1840	Participants received ALXN1840 orally in the 48-week Treatment Period. Participants who completed the 48-week Treatment Period and agreed to enter a 48-week Extension Period, continued to receive ALXN1840. Participants who did not enter the Extension Period discontinued dosing at Week 48, and had a final study visit for safety follow-up at Week 52.

Secondary

Extension Period: Number of Participants With TEAEs

An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An SAE was an AE that met at least 1 of the following criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization for the AE, persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug), important medical event or reaction. The TEAEs were AEs with onset on or after the first study drug dose. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.

Safety Analysis Set in the Extension Period included all participants who received at least 1 dose of ALXN1840 in the Extension Period.

Posted

Count of Participants

Participants

Day 1 (Extension Period) up Week 52 (Extension Period)

ID	Title	Description
OG000	ALXN1840	Participants received ALXN1840 orally in the 48-week Treatment Period. Participants who completed the 48-week Treatment Period and agreed to enter a 48-week Extension Period, continued to receive ALXN1840. Participants who did not enter the Extension Period discontinued dosing at Week 48, and had a final study visit for safety follow-up at Week 52.

Secondary

Treatment Period: Predose Trough Plasma Total Mo Concentration

Pharmacokinetic (PK) Analysis Set in the Treatment Period included all participants who received at least 1 dose of treatment in the Treatment Period and had evaluable PK data for total Mo and/or plasma ultrafiltrate (PUF) Mo (as surrogate measure for ALXN1840 PK) in plasma in the Treatment Period. 'Overall number of participants analyzed' = participants evaluable for this outcome measure. 'Number analyzed' = participants evaluable at specified timepoint.

Posted

Mean

Standard Deviation

nanograms (ng)/milliliter (mL)

Predose up to 4 hours postdose at Week 6 (Day 43) and Week 36 (Day 253)

ID	Title	Description
OG000	ALXN1840	Participants received ALXN1840 orally in the 48-week Treatment Period. Participants who completed the 48-week Treatment Period and agreed to enter a 48-week Extension Period, continued to receive ALXN1840. Participants who did not enter the Extension Period discontinued dosing at Week 48, and had a final study visit for safety follow-up at Week 52.

Units	Counts
Participants	OG000

Secondary

Treatment Period: Predose Trough Plasma Total PUF Mo Concentration

PK Analysis Set in the Treatment Period included all participants who received at least 1 dose of treatment in the Treatment Period and had evaluable PK data for total Mo and/or PUF Mo (as surrogate measure for ALXN1840 PK) in plasma in the Treatment Period. 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

Posted

Mean

Standard Deviation

ng/mL

Predose up to 4 hours postdose at Week 6 (Day 43) and Week 36 (Day 253)

ID	Title	Description
OG000	ALXN1840	Participants received ALXN1840 orally in the 48-week Treatment Period. Participants who completed the 48-week Treatment Period and agreed to enter a 48-week Extension Period, continued to receive ALXN1840. Participants who did not enter the Extension Period discontinued dosing at Week 48, and had a final study visit for safety follow-up at Week 52.

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Mo in Liver Biopsy Specimen at Week 48 (Treatment Period)

The Full Analysis Set in the Treatment Period included all participants who received at least 1 dose of study drug in the Treatment Period and had at least a Baseline liver Cu value evaluable. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Posted

Mean

Standard Deviation

μg/g

Baseline, Week 48 (Treatment Period)

ID	Title	Description
OG000	ALXN1840	Participants received ALXN1840 orally in the 48-week Treatment Period. Participants who completed the 48-week Treatment Period and agreed to enter a 48-week Extension Period, continued to receive ALXN1840. Participants who did not enter the Extension Period discontinued dosing at Week 48, and had a final study visit for safety follow-up at Week 52.

Units	Counts
Participants	OG000

Secondary

Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 48 (Treatment Period)

The CGI-I is a 7-point scale clinician assessment where 1= very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; or 7 = very much worse. Higher scores indicated worsening of disease.

The Full Analysis Set in the Treatment Period included all participants who received at least 1 dose of study drug in the Treatment Period and had at least a Baseline liver Cu value evaluable. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Posted

Mean

Standard Deviation

units on a scale

Week 48 (Treatment Period)

ID	Title	Description
OG000	ALXN1840	Participants received ALXN1840 orally in the 48-week Treatment Period. Participants who completed the 48-week Treatment Period and agreed to enter a 48-week Extension Period, continued to receive ALXN1840. Participants who did not enter the Extension Period discontinued dosing at Week 48, and had a final study visit for safety follow-up at Week 52.

Units	Counts
Participants	OG000

Secondary

Change From Baseline in CGI-S Scale Score at Week 48 (Treatment Period)

The CGI-S is a 7-point scale clinician assessment. Participants were assessed on severity of illness at the time of rating/assessment as follows: 1 = normal, not at all ill; 2 = borderline ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; or 7 = extremely ill. Higher scores indicated worsening of disease.

The Full Analysis Set in the Treatment Period included all participants who received at least 1 dose of study drug in the Treatment Period and had at least a Baseline liver Cu value evaluable. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Posted

Mean

Standard Deviation

units on a scale

Baseline, Week 48 (Treatment Period)

ID	Title	Description
OG000	ALXN1840	Participants received ALXN1840 orally in the 48-week Treatment Period. Participants who completed the 48-week Treatment Period and agreed to enter a 48-week Extension Period, continued to receive ALXN1840. Participants who did not enter the Extension Period discontinued dosing at Week 48, and had a final study visit for safety follow-up at Week 52.

Units	Counts
Participants

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Leukopenia	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0011 affected25 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Tinnitus	Ear and labyrinth disorders	MedDRA 26.0	Systematic Assessment		EG0002 affected31 at risk EG0012 affected25 at risk
Chalazion	Eye disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0011 affected25 at risk
Vision blurred	Eye disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Vitreous detachment	Eye disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Nausea	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment		EG0006 affected31 at risk EG0016 affected25 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment		EG0002 affected31 at risk EG0013 affected25 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment		EG0002 affected31 at risk EG0012 affected25 at risk
Constipation	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment		EG0002 affected31 at risk EG0011 affected25 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment		EG0002 affected31 at risk EG0011 affected25 at risk
Oral pain	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment		EG0002 affected31 at risk EG0010 affected25 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0011 affected25 at risk
Dry mouth	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0012 affected25 at risk
Faeces discoloured	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0011 affected25 at risk
Flatulence	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0012 affected25 at risk
Haemorrhoids thrombosed	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0011 affected25 at risk
Mouth ulceration	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0011 affected25 at risk
Toothache	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0011 affected25 at risk
Vomiting	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Pyrexia	General disorders	MedDRA 26.0	Systematic Assessment		EG0005 affected31 at risk EG0013 affected25 at risk
Fatigue	General disorders	MedDRA 26.0	Systematic Assessment		EG0004 affected31 at risk EG0012 affected25 at risk
Asthenia	General disorders	MedDRA 26.0	Systematic Assessment		EG0002 affected31 at risk EG0012 affected25 at risk
Chills	General disorders	MedDRA 26.0	Systematic Assessment		EG0002 affected31 at risk EG0010 affected25 at risk
Feeling abnormal	General disorders	MedDRA 26.0	Systematic Assessment		EG0002 affected31 at risk EG0012 affected25 at risk
Generalised oedema	General disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0011 affected25 at risk
Pain	General disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Temperature intolerance	General disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0011 affected25 at risk
Hypertransaminasaemia	Hepatobiliary disorders	MedDRA 26.0	Systematic Assessment		EG0002 affected31 at risk EG0012 affected25 at risk
Seasonal allergy	Immune system disorders	MedDRA 26.0	Systematic Assessment		EG0002 affected31 at risk EG0012 affected25 at risk
Immunisation reaction	Immune system disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Nasopharyngitis	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0005 affected31 at risk EG0018 affected25 at risk
COVID-19	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0004 affected31 at risk EG00110 affected25 at risk
Kidney infection	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0002 affected31 at risk EG0010 affected25 at risk
Pneumonia	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0002 affected31 at risk EG0011 affected25 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0002 affected31 at risk EG0014 affected25 at risk
Urinary tract infection	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0002 affected31 at risk EG0011 affected25 at risk
Bacterial vaginosis	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Conjunctivitis	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0011 affected25 at risk
Dermatophytosis	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Folliculitis	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Furuncle	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Gingivitis	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0011 affected25 at risk
Helicobacter infection	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0011 affected25 at risk
Paronychia	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0011 affected25 at risk
Post procedural sepsis	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Respiratory tract infection	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Respiratory tract infection viral	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0011 affected25 at risk
Sinusitis	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0011 affected25 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Head injury	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Incision site pain	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0011 affected25 at risk
Ligament sprain	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0011 affected25 at risk
Post procedural fever	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Post procedural haematuria	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Post procedural hypotension	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Post procedural swelling	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Post vaccination syndrome	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Procedural pain	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0011 affected25 at risk
Road traffic accident	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Upper limb fracture	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0011 affected25 at risk
Alanine aminotransferase increased	Investigations	MedDRA 26.0	Systematic Assessment		EG0008 affected31 at risk EG0018 affected25 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA 26.0	Systematic Assessment		EG0008 affected31 at risk EG0017 affected25 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 26.0	Systematic Assessment		EG0004 affected31 at risk EG0014 affected25 at risk
Hepatic enzyme increased	Investigations	MedDRA 26.0	Systematic Assessment		EG0004 affected31 at risk EG0012 affected25 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 26.0	Systematic Assessment		EG0003 affected31 at risk EG0012 affected25 at risk
Blood creatine phosphokinase increased	Investigations	MedDRA 26.0	Systematic Assessment		EG0003 affected31 at risk EG0014 affected25 at risk
Transaminases increased	Investigations	MedDRA 26.0	Systematic Assessment		EG0003 affected31 at risk EG0012 affected25 at risk
Blood bilirubin increased	Investigations	MedDRA 26.0	Systematic Assessment		EG0002 affected31 at risk EG0011 affected25 at risk
Liver function test increased	Investigations	MedDRA 26.0	Systematic Assessment		EG0002 affected31 at risk EG0012 affected25 at risk
Alanine aminotransferase abnormal	Investigations	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0011 affected25 at risk
Blood albumin decreased	Investigations	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Blood folate decreased	Investigations	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0011 affected25 at risk
Creatinine renal clearance decreased	Investigations	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Creatinine renal clearance increased	Investigations	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0011 affected25 at risk
Protein urine present	Investigations	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Prothrombin time prolonged	Investigations	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Urobilinogen urine increased	Investigations	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Weight decreased	Investigations	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0011 affected25 at risk
Weight increased	Investigations	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0011 affected25 at risk
White blood cell count decreased	Investigations	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0011 affected25 at risk
Hypercholesterolaemia	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment		EG0003 affected31 at risk EG0013 affected25 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment		EG0002 affected31 at risk EG0011 affected25 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Dyslipidaemia	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0012 affected25 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Hypertriglyceridaemia	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0011 affected25 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Iron deficiency	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0011 affected25 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment		EG0003 affected31 at risk EG0014 affected25 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0012 affected25 at risk
Greater trochanteric pain syndrome	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Joint effusion	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0011 affected25 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0011 affected25 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Seborrhoeic keratosis	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Skin papilloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0011 affected25 at risk
Headache	Nervous system disorders	MedDRA 26.0	Systematic Assessment		EG0007 affected31 at risk EG0016 affected25 at risk
Lethargy	Nervous system disorders	MedDRA 26.0	Systematic Assessment		EG0003 affected31 at risk EG0012 affected25 at risk
Dizziness	Nervous system disorders	MedDRA 26.0	Systematic Assessment		EG0002 affected31 at risk EG0012 affected25 at risk
Presyncope	Nervous system disorders	MedDRA 26.0	Systematic Assessment		EG0002 affected31 at risk EG0012 affected25 at risk
Tremor	Nervous system disorders	MedDRA 26.0	Systematic Assessment		EG0002 affected31 at risk EG0011 affected25 at risk
Balance disorder	Nervous system disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Carpal tunnel syndrome	Nervous system disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0011 affected25 at risk
Paraesthesia	Nervous system disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0011 affected25 at risk
Anxiety	Psychiatric disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0012 affected25 at risk
Anxiety disorder	Psychiatric disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0011 affected25 at risk
Depressed mood	Psychiatric disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Depression	Psychiatric disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Insomnia	Psychiatric disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0012 affected25 at risk
Personality disorder	Psychiatric disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Glycosuria	Renal and urinary disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Proteinuria	Renal and urinary disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0011 affected25 at risk
Breast mass	Reproductive system and breast disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0011 affected25 at risk
Breast tenderness	Reproductive system and breast disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0011 affected25 at risk
Dysmenorrhoea	Reproductive system and breast disorders	MedDRA 26.0	Systematic Assessment	The N at risk for this adverse event has been adjusted to the number of females in the respective study periods as it is a sex-specific event.	EG0001 affected11 at risk EG0011 affected9 at risk
Haemorrhagic ovarian cyst	Reproductive system and breast disorders	MedDRA 26.0	Systematic Assessment	The N at risk for this adverse event has been adjusted to the number of females in the respective study periods as it is a sex-specific event.	EG0001 affected11 at risk EG0010 affected9 at risk
Heavy menstrual bleeding	Reproductive system and breast disorders	MedDRA 26.0	Systematic Assessment	The N at risk for this adverse event has been adjusted to the number of females in the respective study periods as it is a sex-specific event.	EG0001 affected11 at risk EG0012 affected9 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0011 affected25 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0011 affected25 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0011 affected25 at risk
Respiratory disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0011 affected25 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0011 affected25 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment		EG0003 affected31 at risk EG0012 affected25 at risk
Diabetic foot	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Idiopathic guttate hypomelanosis	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0011 affected25 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected31 at risk EG0010 affected25 at risk
Ear pain	Ear and labyrinth disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected31 at risk EG0012 affected25 at risk
Myopia	Eye disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected31 at risk EG0011 affected25 at risk
Drug hypersensitivity	Immune system disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected31 at risk EG0011 affected25 at risk
Rhinitis	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0000 affected31 at risk EG0011 affected25 at risk
Neck injury	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment		EG0000 affected31 at risk EG0011 affected25 at risk
Procedural complication	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment		EG0000 affected31 at risk EG0011 affected25 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected31 at risk EG0011 affected25 at risk
Nasal septum deviation	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected31 at risk EG0011 affected25 at risk
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected31 at risk EG0011 affected25 at risk
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected31 at risk EG0011 affected25 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected31 at risk EG0011 affected25 at risk
Gastroenteritis	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0000 affected31 at risk EG0012 affected25 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0000 affected31 at risk EG0012 affected25 at risk
Bacteriuria	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0000 affected31 at risk EG0011 affected25 at risk
Urine analysis abnormal	Investigations	MedDRA 26.0	Systematic Assessment		EG0000 affected31 at risk EG0011 affected25 at risk
Migraine	Nervous system disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected31 at risk EG0011 affected25 at risk
Serotonin syndrome	Nervous system disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected31 at risk EG0011 affected25 at risk
Influenza like illness	General disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected31 at risk EG0011 affected25 at risk
Swelling	General disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected31 at risk EG0011 affected25 at risk
Axillary mass	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected31 at risk EG0011 affected25 at risk
Back disorder	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected31 at risk EG0011 affected25 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected31 at risk EG0011 affected25 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected31 at risk EG0011 affected25 at risk
Gout	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected31 at risk EG0011 affected25 at risk
Hyperlipidaemia	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected31 at risk EG0011 affected25 at risk
Limb injury	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment		EG0000 affected31 at risk EG0011 affected25 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment		EG0000 affected31 at risk EG0011 affected25 at risk
Mixed anxiety and depressive disorder	Psychiatric disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected31 at risk EG0011 affected25 at risk
Suicidal ideation	Psychiatric disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected31 at risk EG0011 affected25 at risk
Respiratory symptom	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected31 at risk EG0011 affected25 at risk
Sinus congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected31 at risk EG0011 affected25 at risk
Ingrown hair	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected31 at risk EG0011 affected25 at risk
Vertigo	Ear and labyrinth disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected31 at risk EG0011 affected25 at risk
Haematuria	Renal and urinary disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected31 at risk EG0011 affected25 at risk

ID	Term
D008107	Liver Diseases
D004066	Digestive System Diseases
D001480	Basal Ganglia Diseases
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D020739	Brain Diseases, Metabolic, Inborn
D001928	Brain Diseases, Metabolic
D009069	Movement Disorders
D020271	Heredodegenerative Disorders, Nervous System
D019636	Neurodegenerative Diseases
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D008661	Metabolism, Inborn Errors
D008664	Metal Metabolism, Inborn Errors
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Treatment Period: ALXN1840	Participants received ALXN1840 orally in the 48-week Treatment Period.	0	31	3	31	30	31
EG001	Extension Period: ALXN1840	Participants who completed the 48-week Treatment Period and agreed to enter a 48-week Extension Period, continued to receive ALXN1840.	0	25	2	25	24	25

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Drug-induced liver injury	Hepatobiliary disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected31 at risk EG0010 affected25 at risk
Hepatic enzyme increased	Investigations	MedDRA 26.0	Systematic Assessment	EG0001 affected31 at risk EG0010 affected25 at risk
Bence Jones proteinuria	Renal and urinary disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected31 at risk EG0010 affected25 at risk
Ureteric obstruction	Renal and urinary disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected31 at risk EG0010 affected25 at risk
Prostatitis	Reproductive system and breast disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected31 at risk EG0010 affected25 at risk
Suicidal ideation	Psychiatric disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected31 at risk EG0011 affected25 at risk
Humerus fracture	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG0000 affected31 at risk EG0011 affected25 at risk