Phase 2 Safety and Efficacy Study of Zilucoplan (RA101495... | NCT03078582

NCT03078582

ID	Type	Description	Link
2016-003522-16	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Zilucoplan (RA101495) treatment naive	Experimental	0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC (treatment naïve)	Drug: Zilucoplan (RA101495)
Zilucoplan (RA101495) previously on eculizumab	Experimental	0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC (previously on eculizumab)	Drug: Zilucoplan (RA101495)

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Zilucoplan (RA101495)	Drug	0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC	Zilucoplan (RA101495) previously on eculizumab

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change-from-baseline in Serum Lactate Dehydrogenase (LDH) Level.	The primary efficacy endpoint is the change-from-baseline in serum LDH levels during this period, defined as the mean LDH values of Weeks 6, 8, 10, and 12 minus the baseline value of LDH.	Through Week 12 of the study

Secondary Outcomes

Measure	Description	Time Frame
Changes From Baseline in Bilirubin Values	Changes from baseline at each of the scheduled post-baseline time-points	Through Week 12 of the study
Total Hemoglobin	Changes from baseline at each of the scheduled post-baseline time-points

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Dr. Anita Hill	St James' Institute of Oncology	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Investigative Site		Gosford	New South Wales		Australia
Investigative Site

References Module

Label	URL
Related Info	View source

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Cohort A (Treatment Naive)	0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC
FG001	Cohort B (Previously on Eculizumab)

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Oct 20, 2016	Feb 8, 2019

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Zilucoplan (RA101495) treatment naive

0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Cohort A (Treatment Naive)	0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC
BG001	Cohort B (Previously on Eculizumab)	0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00010 BG00116 BG00226

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0000 BG0010 BG0020
Between 18 and 65 years

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00059.4± 14.5 BG00149.6± 18.5 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0006 BG0017 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

New Zealand

Title	Measurements
	BG0004 BG0010 BG002

Weight

Mean

Standard Deviation

Title

Denominators

Categories

Title	Measurements
	BG00077.77± 20.64 BG00179.16± 14.86 BG002

Height

Mean

Standard Deviation

Title

Denominators

Categories

Title	Measurements
	BG000168.25± 11.08 BG001171.10± 8.69 BG002

BMI

Mean

Standard Deviation

kg/m2

Title

Denominators

Categories

Title	Measurements
	BG00027.30± 6.15 BG00126.95± 4.14 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change-from-baseline in Serum Lactate Dehydrogenase (LDH) Level.

The primary efficacy endpoint is the change-from-baseline in serum LDH levels during this period, defined as the mean LDH values of Weeks 6, 8, 10, and 12 minus the baseline value of LDH.

Efficacy Evaluable

Posted

Mean

Standard Deviation

U/L

Through Week 12 of the study

ID	Title	Description
OG000	Cohort A (Treatment Naive)	0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC
OG001	Cohort B (Previously on Eculizumab)	0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC

Units	Counts
Participants	OG00010 OG0018

Title

Denominators

Categories

Title	Measurements
	OG000-695.2± 589.2 OG001216.7± 209.2

Secondary

Changes From Baseline in Bilirubin Values

Changes from baseline at each of the scheduled post-baseline time-points

Efficacy Evaluable

Posted

Mean

Standard Deviation

umol/L

Through Week 12 of the study

ID	Title	Description
OG000	Cohort A (Treatment Naive)	0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC
OG001	Cohort B (Previously on Eculizumab)	0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC

Units	Counts
Participants	OG000

Secondary

Total Hemoglobin

Changes from baseline at each of the scheduled post-baseline time-points

Efficacy Evaluable

Posted

Mean

Standard Deviation

g/L

Through Week 12 of the Study

ID	Title	Description
OG000	Cohort A (Treatment Naive)	0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC
OG001	Cohort B (Previously on Eculizumab)	0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC

Units	Counts
Participants	OG000

Secondary

Changes From Baseline in Free Hemoglobin Values

Changes from baseline at each of the scheduled post-baseline time-points

Efficacy Evaluable

Posted

Mean

Standard Deviation

mg/dL

Through Week 12 of the study

ID	Title	Description
OG000	Cohort A (Treatment Naive)	0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC
OG001	Cohort B (Previously on Eculizumab)	0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC

Units	Counts
Participants	OG000

Secondary

Haptoglobin Values

Changes from baseline at each of the scheduled post-baseline time-points

Efficacy Evaluable

Posted

Mean

Standard Deviation

g/L

Through Week 12 of the Study

ID	Title	Description
OG000	Cohort A (Treatment Naive)	0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC
OG001	Cohort B (Previously on Eculizumab)	0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC

Units	Counts
Participants	OG000

Secondary

Reticulocyte Values

Changes from baseline at each of the scheduled post-baseline time-points

Efficacy Evaluable

Posted

Mean

Standard Deviation

10^12 cells/L (SI Units)

Through Week 12 of the Study

ID	Title	Description
OG000	Cohort A (Treatment Naive)	0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC
OG001	Cohort B (Previously on Eculizumab)	0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC

Units	Counts
Participants	OG000

Secondary

Hemoglobinuria Values

Changes from baseline at each of the scheduled post-baseline time-points; Hemoglobinuria was assessed using a urine colorimetric scoring system with a score of 1 through 10. Where 1 represents no hemoglobinuria and 10 represents maximum hemoglobinuria.

Efficacy Evaluable

Posted

Mean

Standard Deviation

score on a scale

Through Week 12 of the Study

ID	Title	Description
OG000	Cohort A (Treatment Naive)	0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC
OG001	Cohort B (Previously on Eculizumab)	0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Cohort A (Treatment Naive)	0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC	0	10	2	10	10	10
EG001	Cohort B (Previously on Eculizumab)	0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC	0	16	1	16	15	16

Serious Adverse Events

Term	Organ System	Assessment Type	Notes	Statistical Information
Pyrexia	General disorders	Systematic Assessment	General disorders and administration site conditions	EG0001 events1 affected10 at risk EG0010 events0 affected0 at risk
Urinary tract Infection	Infections and infestations	Systematic Assessment		EG0000 events0 affected0 at risk EG0011 events1 affected16 at risk
Febrile nonhaemolytic transfusion reaction	Injury, poisoning and procedural complications	Systematic Assessment		EG0001 events1 affected10 at risk EG0010 events0 affected0 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Abdominal Pain	Gastrointestinal disorders	Systematic Assessment	EG0002 events2 affected10 at risk EG0013 events1 affected16 at risk
Abdominal Pain Upper	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected10 at risk EG0013 events3 affected16 at risk
Diarrhoea	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected10 at risk EG0011 events1 affected16 at risk
Constipation	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected16 at risk
Enteritis	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected16 at risk
Nausea	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected16 at risk
Proctalgia	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected16 at risk
Vomiting	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected16 at risk
Haemolysis	Blood and lymphatic system disorders	Systematic Assessment	EG0000 events0 affected10 at risk EG0017 events7 affected16 at risk
Anaemia	Blood and lymphatic system disorders	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected16 at risk
Fatigue	General disorders	Systematic Assessment	EG0001 events1 affected10 at risk EG0013 events3 affected16 at risk
Injection site bruising	General disorders	Systematic Assessment	EG0003 events3 affected10 at risk EG0011 events1 affected16 at risk
Asthenia	General disorders	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected16 at risk
Chest pain	General disorders	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected16 at risk
Crepitations	General disorders	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected16 at risk
Influenza like illness	General disorders	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected16 at risk
Vaccination site pain	General disorders	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected16 at risk
Upper respiratory tract infection	Infections and infestations	Systematic Assessment	EG0003 events3 affected10 at risk EG0011 events1 affected16 at risk
Localised infection	Infections and infestations	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected16 at risk
Rhinitis	Infections and infestations	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected16 at risk
Urosepsis	Infections and infestations	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected16 at risk
Vulvovaginal mycotic infection	Infections and infestations	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected16 at risk
Contusion	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected16 at risk
Febrile nonhaemolytic transfusion reaction	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected16 at risk
Tooth fracture	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected16 at risk
Blood glucose fluctuation	Investigations	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected16 at risk
Blood lactate dehydrogenase increased	Investigations	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected16 at risk
Haemoglobin decreased	Investigations	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected16 at risk
Liver function test increased	Investigations	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected16 at risk
Decreased appetite	Metabolism and nutrition disorders	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected16 at risk
Back pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0002 events1 affected10 at risk EG0016 events3 affected16 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 events0 affected10 at risk EG0012 events2 affected16 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 events0 affected10 at risk EG0013 events2 affected16 at risk
Flank pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected16 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 events0 affected10 at risk EG0012 events1 affected16 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0002 events1 affected10 at risk EG0010 events0 affected16 at risk
Myalgia	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected16 at risk
Headache	Nervous system disorders	Systematic Assessment	EG0003 events1 affected10 at risk EG00117 events7 affected16 at risk
Dizziness	Nervous system disorders	Systematic Assessment	EG0002 events2 affected10 at risk EG0013 events3 affected16 at risk
Dysgeusia	Nervous system disorders	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected16 at risk
Presyncope	Nervous system disorders	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected16 at risk
Syncope	Nervous system disorders	Systematic Assessment	EG0002 events1 affected10 at risk EG0010 events0 affected16 at risk
Device failure	Product Issues	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected16 at risk
Agitation	Psychiatric disorders	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected16 at risk
Anxiety	Psychiatric disorders	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected16 at risk
Insomnia	Psychiatric disorders	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected16 at risk
Sleep disorder	Psychiatric disorders	Systematic Assessment	EG0002 events1 affected10 at risk EG0010 events0 affected16 at risk
Paroxysmal nocturnal haemoglobinuria	Renal and urinary disorders	Systematic Assessment	EG0001 events1 affected10 at risk EG0012 events2 affected16 at risk
Vaginal discharge	Reproductive system and breast disorders	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected16 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0002 events2 affected10 at risk EG0010 events0 affected16 at risk
Cough	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected16 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected16 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected10 at risk EG0014 events1 affected16 at risk
Actinic keratosis	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected16 at risk
Lymphoedema	Vascular disorders	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected16 at risk

ID	Term
D006457	Hemoglobinuria, Paroxysmal

ID	Term
C000719268	zilucoplan

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