An Open-label Safety and Efficacy Study of Recombinant FV... | NCT02172950

NCT02172950

ID	Type	Description	Link
2013-003262-13	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
Previously treated patients (PTPs)	Experimental	The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule for the subject based upon the subject's pharmacokinetic (PK) profile, rVIII-SingleChain PK data, previous FVIII treatment regimen, and bleeding phenotype, if available.	Biological: rVIII-SingleChain
Previously untreated patients (PUPs)	Experimental	The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics.	Biological: rVIII-SingleChain

Interventions

Name	Type	Description	Arm Group Labels	Other Names
rVIII-SingleChain	Biological	Recombinant single-chain coagulation factor VIII	Previously treated patients (PTPs) Previously untreated patients (PUPs)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Incidence of Inhibitor Formation to FVIII in Previously Treated Patients (PTPs) With 100 Exposure Days (EDs) to CSL627		At the closest visit after 100 EDs (up to 5 years).
Number of Previously Untreated Patients (PUPs) With High-titer Inhibitor Formation to FVIII With at Least 50 EDs to CSL627	High-titer inhibitor is defined as an inhibitor titer of ≥ 5 Bethesda units/mL.	At the closest visit after 50 EDs (up to 5 years).
Percent Treatment Success for Major Bleeding Episodes in PUPs	Percentage of major bleeding episodes treated successfully where treatment success for a bleeding episode is defined as a rating of "excellent" or "good" on the investigator's clinical assessment of hemostatic efficacy 4-point scale "excellent, good, moderate or poor/no response". Major bleeding episodes are defined as bleeding episodes for which a subject is required to seek treatment at the hemophilia center or that threatens the subject's life or loss of limb.	Up to 5 years
Annualized Spontaneous Bleeding Rate in PUPs	The annualized spontaneous bleeding rate for PUPs taking prophylaxis and on-demand treatment regimens.	Up to 5 years

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Bleeding Episodes Treated Successfully in PTPs	Percentage of bleeding episodes treated successfully where treatment success for a bleeding episode is defined as a rating of "excellent" or "good" on the investigator's clinical assessment of hemostatic efficacy 4-point scale "excellent, good, moderate or poor/no response".	Up to 5 years

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Program Director	CSL Behring	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Study Site 8400213		San Diego	California	92103-8651	United States
Study Site 8400241

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Previously Treated Patients (PTPs)	The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule for the subject based upon the subject's pharmacokinetic (PK) profile, rVIII-SingleChain PK data, previous FVIII treatment regimen, and bleeding phenotype, if available. rVIII-SingleChain: Recombinant single-chain coagulation factor VIII

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	May 26, 2020	Aug 30, 2021

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

No data available

No data is available for this block.

Masking Info

Age was analyzed separately as PTPs and PUPs

Arm/Group Information

ID	Title	Description
BG000	Previously Treated Patients (PTPs)	The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule for the subject based upon the subject's pharmacokinetic (PK) profile, rVIII-SingleChain PK data, previous FVIII treatment regimen, and bleeding phenotype, if available. rVIII-SingleChain: Recombinant single-chain coagulation factor VIII
BG001	Previously Untreated Patients (PUPs)	The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics. rVIII-SingleChain: Recombinant single-chain coagulation factor VIII
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
	OG0000

Primary

Number of Previously Untreated Patients (PUPs) With High-titer Inhibitor Formation to FVIII With at Least 50 EDs to CSL627

High-titer inhibitor is defined as an inhibitor titer of ≥ 5 Bethesda units/mL.

Posted

Number

participants

At the closest visit after 50 EDs (up to 5 years).

ID	Title	Description
OG000	CSL627: Previously Untreated Patients (PUPs)	The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics. rVIII-SingleChain: Recombinant single-chain coagulation factor VIII

Units	Counts
Participants	OG000

Primary

Percent Treatment Success for Major Bleeding Episodes in PUPs

Percentage of major bleeding episodes treated successfully where treatment success for a bleeding episode is defined as a rating of "excellent" or "good" on the investigator's clinical assessment of hemostatic efficacy 4-point scale "excellent, good, moderate or poor/no response". Major bleeding episodes are defined as bleeding episodes for which a subject is required to seek treatment at the hemophilia center or that threatens the subject's life or loss of limb.

Efficacy population (EP) - comprised all subjects in the Safety Population who received at least 1 dose of rVIII-SingleChain (CSL627) for either routine prophylaxis treatment or on-demand treatment during the study. This endpoint was analyzed for PUPs only.

Posted

Number

percentage of treatment success

Up to 5 years

Major bleeds

ID	Title	Description
OG000	CSL627: Previously Untreated Patients (PUPs)	The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics. rVIII-SingleChain: Recombinant single-chain coagulation factor VIII

Units

Primary

Annualized Spontaneous Bleeding Rate in PUPs

The annualized spontaneous bleeding rate for PUPs taking prophylaxis and on-demand treatment regimens.

EP. This endpoint was analyzed for PUPs only.

Posted

Mean

Standard Deviation

Number of Spontaneous bleeds per year

Up to 5 years

ID	Title	Description
OG000	CSL627: Previously Untreated Patients (PUPs)	The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics. rVIII-SingleChain: Recombinant single-chain coagulation factor VIII

Units	Counts
Participants	OG000

Secondary

Percentage of Bleeding Episodes Treated Successfully in PTPs

Posted

Number

99% Confidence Interval

Percentage of treated bleeding events

Up to 5 years

Number of treated bleeding events

ID	Title	Description
OG000	CSL627: Previously Treated Patients (PTPs)	The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule for the subject based upon the subject's pharmacokinetic (PK) profile, rVIII-SingleChain PK data, previous FVIII treatment regimen, and bleeding phenotype, if available. rVIII-SingleChain: Recombinant single-chain coagulation factor VIII

Units	Counts
Participants	OG000

Secondary

Annualized Bleeding Rate in PTPs and PUPs

The annualized bleeding rate for PTPs and PUPs taking prophylaxis and on-demand treatment regimens

Posted

Mean

Standard Deviation

Number of bleeds per year

Up to 5 years

ID	Title	Description
OG000	CSL627: Previously Treated Patients (PTPs)	The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule for the subject based upon the subject's pharmacokinetic (PK) profile, rVIII-SingleChain PK data, previous FVIII treatment regimen, and bleeding phenotype, if available. rVIII-SingleChain: Recombinant single-chain coagulation factor VIII
OG001	CSL627: Previously Untreated Patients (PUPs)	The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics. rVIII-SingleChain: Recombinant single-chain coagulation factor VIII

Secondary

Percentage of Bleeding Episodes Requiring 1, 2, 3, or > 3 Injections of CSL627 to Achieve Hemostasis in PTPs and PUPs

Posted

Number

Percentage of treated bleeds

Up to 5 years

Treated bleeds

ID	Title	Description
OG000	CSL627: Previously Treated Patients (PTPs)	The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule for the subject based upon the subject's pharmacokinetic (PK) profile, rVIII-SingleChain PK data, previous FVIII treatment regimen, and bleeding phenotype, if available. rVIII-SingleChain: Recombinant single-chain coagulation factor VIII
OG001	CSL627: Previously Untreated Patients (PUPs)	The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics. rVIII-SingleChain: Recombinant single-chain coagulation factor VIII

Secondary

Mean Number of On-demand Infusions of CSL627

EP. This endpoint analyzes PTPs and PUPs that received on-demand treatment.

Posted

Mean

Standard Deviation

Number of infusions

Up to 5 years

ID	Title	Description
OG000	CSL627: Previously Treated Patients (PTPs)	The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule for the subject based upon the subject's pharmacokinetic (PK) profile, rVIII-SingleChain PK data, previous FVIII treatment regimen, and bleeding phenotype, if available. rVIII-SingleChain: Recombinant single-chain coagulation factor VIII
OG001	CSL627: Previously Untreated Patients (PUPs)	The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics. rVIII-SingleChain: Recombinant single-chain coagulation factor VIII

Secondary

Mean On-demand Dose Administered of CSL627

EP. This endpoint analyzes PTPs and PUPs that received on-demand treatment.

Posted

Mean

Standard Deviation

IU/kg

Up to 5 years

ID	Title	Description
OG000	CSL627: Previously Treated Patients (PTPs)	The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule for the subject based upon the subject's pharmacokinetic (PK) profile, rVIII-SingleChain PK data, previous FVIII treatment regimen, and bleeding phenotype, if available. rVIII-SingleChain: Recombinant single-chain coagulation factor VIII
OG001	CSL627: Previously Untreated Patients (PUPs)	The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics. rVIII-SingleChain: Recombinant single-chain coagulation factor VIII

Units

Secondary

Mean Prophylaxis Dose Administered of CSL627

EP. This endpoint analyzes PTPs and PUPs that received prophylaxis treatment.

Posted

Mean

Standard Deviation

IU/kg

Up to 5 years

ID	Title	Description
OG000	CSL627: Previously Treated Patients (PTPs)	The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule for the subject based upon the subject's pharmacokinetic (PK) profile, rVIII-SingleChain PK data, previous FVIII treatment regimen, and bleeding phenotype, if available. rVIII-SingleChain: Recombinant single-chain coagulation factor VIII
OG001	CSL627: Previously Untreated Patients (PUPs)	The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics. rVIII-SingleChain: Recombinant single-chain coagulation factor VIII

Units

Secondary

Mean Total Amount of CSL627 Administered During Surgery Period in PTPs

Surgery population

Posted

Mean

Standard Deviation

Day of surgery up to 336 hours post-surgery

ID	Title	Description
OG000	CSL627: Previously Treated Patients (PTPs)	The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule for the subject based upon the subject's pharmacokinetic (PK) profile, rVIII-SingleChain PK data, previous FVIII treatment regimen, and bleeding phenotype, if available. rVIII-SingleChain: Recombinant single-chain coagulation factor VIII

Units	Counts
Participants	OG000

Secondary

Total Amount of CSL627 Administered During Surgery Period in PUPs

Surgery population

Posted

Number

Day of surgery up to 336 hours post-surgery

ID	Title	Description
OG000	CSL627: Previously Untreated Patients (PUPs)	The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics. rVIII-SingleChain: Recombinant single-chain coagulation factor VIII

Units	Counts
Participants	OG000

Secondary

Hemostatic Efficacy of rVIII-SingleChain for PTPs and PUPs Who Undergo Surgery

The investigator will rate the efficacy of the rVIII-SingleChain treatment during surgery based on a hemostatic efficacy four point rating scale of "excellent, good, moderate or poor/no response".

Surgery population - comprised all subjects in the Safety Population who received at least 1 dose of rVIII-SingleChain for surgical prophylaxis

Posted

Number

Number of surgeries

From the start of surgery through the post-operative recovery (generally up to 14 days after surgery)

Surgeries

ID	Title	Description
OG000	CSL627: Previously Treated Patients (PTPs)	The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule for the subject based upon the subject's pharmacokinetic (PK) profile, rVIII-SingleChain PK data, previous FVIII treatment regimen, and bleeding phenotype, if available. rVIII-SingleChain: Recombinant single-chain coagulation factor VIII
OG001	CSL627: Previously Untreated Patients (PUPs)	The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics. rVIII-SingleChain: Recombinant single-chain coagulation factor VIII

Secondary

Incidence of Inhibitor Formation to FVIII in PTPs After 10 EDs and After 50 EDs

Posted

Number

percentage of participants

Up to 5 years

ID	Title	Description
OG000	CSL627: Previously Treated Patients (PTPs)	The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule for the subject based upon the subject's pharmacokinetic (PK) profile, rVIII-SingleChain PK data, previous FVIII treatment regimen, and bleeding phenotype, if available. rVIII-SingleChain: Recombinant single-chain coagulation factor VIII

Units	Counts
Participants	OG000

Secondary

Percentage of PTPs and PUPs Developing Antibodies Against CSL627

Posted

Number

percentage of participants

PTPs: At the closest visit after 100 EDs (up to 5 years). PUPs: At the closest visit after 50 EDs (up to 5 years).

ID	Title	Description
OG000	CSL627: Previously Treated Patients (PTPs)	The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule for the subject based upon the subject's pharmacokinetic (PK) profile, rVIII-SingleChain PK data, previous FVIII treatment regimen, and bleeding phenotype, if available. rVIII-SingleChain: Recombinant single-chain coagulation factor VIII
OG001	CSL627: Previously Untreated Patients (PUPs)	The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics. rVIII-SingleChain: Recombinant single-chain coagulation factor VIII

Secondary

Percentage of PTPs and PUPs Developing Antibodies to Chinese Hamster Ovary (CHO) Proteins

Posted

Number

percentage of participants

PTPs: At the closest visit after 100 EDs (up to 5 years). PUPs: At the closest visit after 50 EDs (up to 5 years).

ID	Title	Description
OG000	CSL627: Previously Treated Patients (PTPs)	The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule for the subject based upon the subject's pharmacokinetic (PK) profile, rVIII-SingleChain PK data, previous FVIII treatment regimen, and bleeding phenotype, if available. rVIII-SingleChain: Recombinant single-chain coagulation factor VIII
OG001	CSL627: Previously Untreated Patients (PUPs)	The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics. rVIII-SingleChain: Recombinant single-chain coagulation factor VIII

Secondary

Number of PUPs With High-titer Inhibitor Formation to FVIII After 10 EDs With CSL627

High-titer inhibitor is defined as an inhibitor titer of ≥ 5 Bethesda units/mL.

Posted

Number

participants

At the closest visit after 10 EDs (up to 5 years)

ID	Title	Description
OG000	CSL627: Previously Untreated Patients (PUPs)	The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics. rVIII-SingleChain: Recombinant single-chain coagulation factor VIII

Units	Counts
Participants	OG000

Secondary

Number of PUPs With Low-titer Inhibitor Formation to FVIII After 10 EDs and After 50 EDs With CSL627

Low-titer inhibitor is defined as an inhibitor titer of less than 5 Bethesda units/mL.

Posted

Number

participants

At the closest visit after 10 and after 50 EDs (up to 5 years)

ID	Title	Description
OG000	CSL627: Previously Untreated Patients (PUPs)	The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics. rVIII-SingleChain: Recombinant single-chain coagulation factor VIII

Units	Counts
Participants	OG000

Secondary

Incidence of Total Inhibitor Formation to FVIII in PUPs

Posted

Number

percentage of participants

Up to 5 years

ID	Title	Description
OG000	CSL627: Previously Untreated Patients (PUPs)	The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics. rVIII-SingleChain: Recombinant single-chain coagulation factor VIII

Units	Counts
Participants	OG000

Secondary

Percent Treatment Success for Non-major Bleeding Episodes in PUPs

Percentage of bleeding episodes treated successfully where treatment success for a bleeding episode is defined as a rating of "excellent" or "good" on the investigator's clinical assessment of hemostatic efficacy 4-point scale "excellent, good, moderate or poor/no response". Non-major bleeding episodes are those not requiring treatment at the hemophilia center or not threatening subject's life or loss of limb.

EP. This endpoint was analyzed for PUPs only.

Posted

Number

95% Confidence Interval

percentage of treated bleeding events

Up to 5 years

Treated bleeding events

ID	Title	Description
OG000	CSL627: Previously Untreated Patients (PUPs)	The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics. rVIII-SingleChain: Recombinant single-chain coagulation factor VIII

Units	Counts
Participants

Secondary

Percentage of PUPs With Clinically Significant Abnormal Vital Signs Values After First Infusion of CSL627

Vital signs assessments include heart rate, blood pressure, and body temperature. Clinical significance of an abnormality will be assessed by the investigator.

SP. This endpoint was analyzed for PUPs only.

Posted

Number

percentage of participants

Up to 6 hours after first infusion

ID	Title	Description
OG000	CSL627: Previously Untreated Patients (PUPs)	The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics. rVIII-SingleChain: Recombinant single-chain coagulation factor VIII

Units	Counts
Participants	OG000

Secondary

Percentage of PUPs With Treatment-emergent Clinically Significant Abnormal Vital Signs Values

Vital signs assessments include heart rate, blood pressure, and body temperature. Clinical significance of an abnormality will be assessed by the investigator.

SP. This endpoint was analyzed for PUPs only.

Posted

Number

percentage of participants

Up to 5 years

ID	Title	Description
OG000	CSL627: Previously Untreated Patients (PUPs)	The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics. rVIII-SingleChain: Recombinant single-chain coagulation factor VIII

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	CSL627: Previously Treated Patients (PTPs)	The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule for the subject based upon the subject's pharmacokinetic (PK) profile, rVIII-SingleChain PK data, previous FVIII treatment regimen, and bleeding phenotype, if available. rVIII-SingleChain: Recombinant single-chain coagulation factor VIII	1	222	23	222	130	222
EG001	CSL627: Previously Untreated Patients (PUPs)	The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics. rVIII-SingleChain: Recombinant single-chain coagulation factor VIII	0	24	14	24	23	24

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Shock	Vascular disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected222 at risk EG0010 events0 affected24 at risk
Vasospasm	Vascular disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected222 at risk EG0010 events0 affected24 at risk
Haemorrhage	Vascular disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected222 at risk EG0011 events1 affected24 at risk
Road traffic accident	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0002 events2 affected222 at risk EG0010 events0 affected24 at risk
Abdominal injury	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected222 at risk EG0010 events0 affected24 at risk
Periprosthetic fracture	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected222 at risk EG0010 events0 affected24 at risk
Skin laceration	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected222 at risk EG0010 events0 affected24 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected222 at risk EG0012 events2 affected24 at risk
Wound haemorrhage	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected222 at risk EG0011 events1 affected24 at risk
Anti factor VIII antibody positive	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected222 at risk EG0016 events6 affected24 at risk
Inhibiting antibodies positive	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected222 at risk EG0015 events5 affected24 at risk
Factor VIII inhibition	Blood and lymphatic system disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected222 at risk EG0011 events1 affected24 at risk
Pregnancy of partner	Social circumstances	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected222 at risk EG0010 events0 affected24 at risk
Generalised tonic-clonic seizure	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected222 at risk EG0010 events0 affected24 at risk
Lennox-Gastaut syndrome	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected222 at risk EG0010 events0 affected24 at risk
Seizure	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected222 at risk EG0010 events0 affected24 at risk
Blindness transient	Eye disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected222 at risk EG0010 events0 affected24 at risk
Chest pain	General disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected222 at risk EG0010 events0 affected24 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected222 at risk EG0010 events0 affected24 at risk
Duodenal ulcer	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected222 at risk EG0010 events0 affected24 at risk
Gastritis erosive	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected222 at risk EG0010 events0 affected24 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected222 at risk EG0010 events0 affected24 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected222 at risk EG0010 events0 affected24 at risk
Mouth haemorrhage	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected222 at risk EG0011 events1 affected24 at risk
Nephritis	Renal and urinary disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected222 at risk EG0010 events0 affected24 at risk
Haemophilic arthropathy	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0003 events3 affected222 at risk EG0010 events0 affected24 at risk
Muscle haemorrhage	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected222 at risk EG0010 events0 affected24 at risk
Musculoskeletal stiffness	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected222 at risk EG0010 events0 affected24 at risk
Tendinous contracture	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected222 at risk EG0010 events0 affected24 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected222 at risk EG0011 events1 affected24 at risk
Appendicitis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0002 events2 affected222 at risk EG0010 events0 affected24 at risk
Cellulitis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected222 at risk EG0010 events0 affected24 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected222 at risk EG0010 events0 affected24 at risk
Pneumonia	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected222 at risk EG0010 events0 affected24 at risk
Wound infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected222 at risk EG0010 events0 affected24 at risk
Device related infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected222 at risk EG0011 events1 affected24 at risk
Acinetobacter infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected222 at risk EG0011 events1 affected24 at risk
Influenza	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected222 at risk EG0010 events0 affected24 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Haematoma	Vascular disorders	MedDRA 21.1	Systematic Assessment	EG0002 events2 affected222 at risk EG0013 events2 affected24 at risk
Allergy to arthropod sting	Immune system disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected222 at risk EG0015 events2 affected24 at risk
Pyrexia	General disorders	MedDRA 21.1	Systematic Assessment	EG00018 events14 affected222 at risk EG00144 events15 affected24 at risk
Malaise	General disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected222 at risk EG0014 events2 affected24 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG00012 events11 affected222 at risk EG0015 events3 affected24 at risk
Head injury	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG00011 events11 affected222 at risk EG0013 events1 affected24 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG00013 events11 affected222 at risk EG0010 events0 affected24 at risk
Coronavirus test positive	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected222 at risk EG0012 events2 affected24 at risk
Inhibiting antibodies positive	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected222 at risk EG0012 events2 affected24 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG00019 events13 affected222 at risk EG00113 events6 affected24 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0003 events3 affected222 at risk EG0013 events2 affected24 at risk
Bronchospasm	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected222 at risk EG0014 events2 affected24 at risk
Iron deficiency anaemia	Blood and lymphatic system disorders	MedDRA 21.1	Systematic Assessment	EG0003 events2 affected222 at risk EG0013 events3 affected24 at risk
Headache	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG00029 events20 affected222 at risk EG0010 events0 affected24 at risk
Ear pain	Ear and labyrinth disorders	MedDRA 21.1	Systematic Assessment	EG0004 events4 affected222 at risk EG0012 events2 affected24 at risk
Dental caries	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG00011 events11 affected222 at risk EG0010 events0 affected24 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0005 events5 affected222 at risk EG0016 events5 affected24 at risk
Vomiting	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0005 events4 affected222 at risk EG0018 events3 affected24 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0006 events6 affected222 at risk EG0013 events3 affected24 at risk
Eczema	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected222 at risk EG0013 events3 affected24 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG00028 events20 affected222 at risk EG0011 events1 affected24 at risk
Joint swelling	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0005 events4 affected222 at risk EG0012 events2 affected24 at risk
Haemarthrosis	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0003 events2 affected222 at risk EG0012 events2 affected24 at risk
Nasopharyngitis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG00073 events40 affected222 at risk EG00115 events9 affected24 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG00037 events25 affected222 at risk EG00118 events7 affected24 at risk
Influenza	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG00016 events14 affected222 at risk EG0016 events4 affected24 at risk
Tonsillitis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG00017 events13 affected222 at risk EG0015 events5 affected24 at risk
Rhinitis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0007 events7 affected222 at risk EG00110 events6 affected24 at risk
Ear infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0008 events5 affected222 at risk EG0019 events5 affected24 at risk
Conjunctivitis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0006 events6 affected222 at risk EG0014 events3 affected24 at risk
Bronchitis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0007 events5 affected222 at risk EG0013 events3 affected24 at risk
Varicella	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0002 events2 affected222 at risk EG0017 events6 affected24 at risk
Otitis media	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0005 events3 affected222 at risk EG0015 events4 affected24 at risk
Viral rhinitis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected222 at risk EG0012 events2 affected24 at risk
Scarlet fever	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected222 at risk EG0012 events2 affected24 at risk
Tinea capitis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected222 at risk EG0012 events2 affected24 at risk

ID	Term
D006467	Hemophilia A

Ancestor Terms

ID	Term
D025861	Blood Coagulation Disorders, Inherited
D001778	Blood Coagulation Disorders
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D020147	Coagulation Protein Disorders
D006474	Hemorrhagic Disorders
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Units	Counts
Participants	OG000222 OG00123

Participants	OG000222 OG00124
Treated bleeds	OG0002413 OG001315