Download PDF

Clinical Trial Results:
Prospective, open-label, uncontrolled, Phase III study to assess the efficacy and safety of Octafibrin for on-demand treatment of acute bleeding and to prevent bleeding during and after surgery in subjects with congenital fibrinogen deficiency.

Summary
EudraCT number	2011-002419-27
Trial protocol	GB BG
Global end of trial date	14 Feb 2018

Results information
Results version number	v1(current)
This version publication date	16 Feb 2019
First version publication date	16 Feb 2019
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

FORMA-02

ISRCTN number

US NCT number

NCT02267226

WHO universal trial number (UTN)

Sponsor organisation name

Octapharma AG

Sponsor organisation address

Seidenstrasse 2, Lachen, Switzerland, 8853

Public contact

Bruce SCHWARTZ. PhD, Octapharma AG, bruce.schwartz@octapharma.com

Scientific contact

Bruce SCHWARTZ. PhD, Octapharma AG, bruce.schwartz@octapharma.com

Is trial part of an agreed paediatric investigation plan (PIP)

Yes

EMA paediatric investigation plan number(s)

EMEA-001208-PIP01-11

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

13 Sep 2018

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

14 Feb 2018

Was the trial ended prematurely?

Main objective of the trial

The study aims to demonstrate the efficacy of Octafibrin for on-demand treatment of acute bleeding episodes (spontaneous or after trauma).

Protection of trial subjects

This trial was conducted in accordance to the principles of GCP, ensuring that the rights, safety and well-being of patients are protected and in consistency with the Declaration of Helsinki. Inclusion and exclusion criteria were carefully defined in order to protect subjects from contraindications, interactions with other medication and risk factors associated with the investigational medicinal product. Throughout the study safety was assessed, such as occurrence of AEs, safety labs and vital signs.

Background therapy

Evidence for comparator

Actual start date of recruitment

13 Oct 2014

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United Kingdom: 3

Country: Number of subjects enrolled

Bulgaria: 2

Country: Number of subjects enrolled

United States: 1

Country: Number of subjects enrolled

Turkey: 2

Country: Number of subjects enrolled

Saudi Arabia: 1

Country: Number of subjects enrolled

Lebanon: 7

Country: Number of subjects enrolled

Russian Federation: 1

Country: Number of subjects enrolled

India: 5

Country: Number of subjects enrolled

Iran, Islamic Republic of: 3

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Screening details

Patients with documented diagnosis of congenital fibrinogen deficiency, expected to require on-demand treatment for bleeding or surgical prophylaxis were screened according to predefined in- and exclusion criteria.

Period 1 title

Overall Trial (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Octafibrin

Arm description

Arm type

Experimental

Investigational medicinal product name

Octafibrin

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for injection

Routes of administration

Intravenous use

Dosage and administration details

It was administered as an intravenous bolus injection at a maximum speed of 5 mL/min. Continuous infusion was not allowed. Octafibrin was recommended to be individually dosed to achieve a target fibrinogen plasma level dependent on the bleeding type (minor or major) or type of surgery (minor or major) as defined per protocol.

Number of subjects in period 1	Octafibrin
Started	25
Completed	18
Not completed	7
Physician decision	1
PI decided to close the site	2
Sponsor Request	4

Baseline characteristics

Top of page

Reporting group title

Overall Trial

Reporting group description

Reporting group values	Overall Trial	Total
Number of subjects	25	25
Age categorical
Units: Subjects
In utero	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0
Newborns (0-27 days)	0	0
Infants and toddlers (28 days-23 months)	0	0
Children (2-11 years)	0	0
Adolescents (12-17 years)	6	6
Adults (18-64 years)	19	19
From 65-84 years	0	0
85 years and over	0	0
Age continuous
Units: years
geometric mean (full range (min-max))	29.04 (12 to 54)	-
Gender categorical
Units: Subjects
Female	11	11
Male	14	14

Subject analysis set title

Safety Population

Subject analysis set type

Full analysis

Subject analysis set description

All patients who fulfilled all the inclusion criteria and met none of the exclusion criteria for the study and who received at least one infusion of Octafibrin

Subject analysis set title

Full analysis set (FAS)-Bleeding population

Subject analysis set type

Full analysis

Subject analysis set description

The FAS defined according to the intention-to-treat (ITT) principle included patients in the Safety population who presented with an episode of acute bleeding and received at least one infusion of Octafibrin for treatment of a Bleeding Episode (BE)

Subject analysis set title

Surgical Prophylaxis population

Subject analysis set type

Sub-group analysis

Subject analysis set description

Patients in the Safety population who underwent a surgical procedure with a need for at least one infusion of Octafibrin.

Subject analysis set title

Investigator Assessment

Subject analysis set type

Sub-group analysis

Subject analysis set description

Efficacy as assessed by the investigator

Subject analysis set title

IDMEAC Assessment

Subject analysis set type

Sub-group analysis

Subject analysis set description

Efficacy as assessed by the IDMEAC

Subject analysis sets values	Safety Population	Full analysis set (FAS)-Bleeding population	Surgical Prophylaxis population	Investigator Assessment	IDMEAC Assessment
Number of subjects	25	24	9	24	24
Age categorical
Units: Subjects
In utero
Preterm newborn infants (gestational age < 37 wks)
Newborns (0-27 days)
Infants and toddlers (28 days-23 months)
Children (2-11 years)
Adolescents (12-17 years)	6	6	1	6	6
Adults (18-64 years)	19	18	8	18	18
From 65-84 years
85 years and over
Age continuous
Units: years
geometric mean (full range (min-max))	29.04 (12 to 54)	28.5 (12 to 54)	31 (12 to 49)	28.5 (12 to 54)	28.5 (12 to 54)
Gender categorical
Units: Subjects
Female	11	11	2	11	11
Male	14	13	7	13	13

End points

Top of page

Reporting group title

Octafibrin

Reporting group description

Subject analysis set title

Safety Population

Subject analysis set type

Full analysis

Subject analysis set description

All patients who fulfilled all the inclusion criteria and met none of the exclusion criteria for the study and who received at least one infusion of Octafibrin

Subject analysis set title

Full analysis set (FAS)-Bleeding population

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

Surgical Prophylaxis population

Subject analysis set type

Sub-group analysis

Subject analysis set description

Patients in the Safety population who underwent a surgical procedure with a need for at least one infusion of Octafibrin.

Subject analysis set title

Investigator Assessment

Subject analysis set type

Sub-group analysis

Subject analysis set description

Efficacy as assessed by the investigator

Subject analysis set title

IDMEAC Assessment

Subject analysis set type

Sub-group analysis

Subject analysis set description

Efficacy as assessed by the IDMEAC

Primary: Haemostatic Efficacy in On-Demand Treatment of the First Bleeding Episode

Top of page

End point title

Haemostatic Efficacy in On-Demand Treatment of the First Bleeding Episode ^[1]

End point description

The investigator's overall clinical assessment of haemostatic efficacy for bleeding was based on a 4 point haemostatic efficacy scale. The final efficacy assessment of each patient was adjudicated by the Independent Data Monitoring & Endpoint Adjudication Committee (IDMEAC). The success rate was calculated as the proportion of patients with treatment success. The 90% CI for the success rate was calculated according to Blyth–Still–Casella interval for the proportion of patients with successful haemostatic efficacy with the predefined threshold of 0.7; values were manually rounded.

End point type

Primary

End point timeframe

The first bleeding episode covers the time period from the first Octafibrin infusion until 24 hours (i.e., 1 day) after the last infusion.

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Analysis of data was descriptive. Continuous variables were summarized using descriptive statistics (arithm. mean, standard deviation (SD), median, min/max, number of observations and missing observations). Categorical variables were summarized with counts and percentages. 90% CI for success rate was calculated according to Blyth–Still–Casella interval for the proportion of patients with successful haemostatic efficacy with a predefined threshold of 0.7. Values were manually rounded.

End point values	Investigator Assessment	IDMEAC Assessment
Number of subjects analysed	24	24
Units: Number of patients
number (not applicable)
Excellent	19	23
Good	5	1
Moderate	0	0
None	0	0
Success rate (%)	100	100
Success rate (90% confidence interval [CI]) lower	0.885	0.885
Success rate (90% confidence interval [CI]) upper	1.000	1.000

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Start of the first Octafibrin infusion until the end of each 30-day observation and follow-up period for on-demand treatment or until the Last Post-Operative Day in surgeries.

Adverse event reporting additional description

AEs occurring between the start of the first Octafibrin infusion and the end of each 30-day observation and follow-up period and during the surgical follow-up were recorded as treatment-emergent adverse events (TEAEs). Non-TEAEs were all AEs not falling into the follow-up periods.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

18.1

Reporting group title

Octafibrin

Reporting group description

Serious adverse events	Octafibrin
Total subjects affected by serious adverse events
subjects affected / exposed	5 / 25 (20.00%)
number of deaths (all causes)	0
number of deaths resulting from adverse events	0
Injury, poisoning and procedural complications
Ligament rupture
subjects affected / exposed	1 / 25 (4.00%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Patella fracture
subjects affected / exposed	1 / 25 (4.00%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Ligament sprain
subjects affected / exposed	1 / 25 (4.00%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Transfusion reaction
subjects affected / exposed	1 / 25 (4.00%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Vascular disorders
Accelerated hypertension
subjects affected / exposed	1 / 25 (4.00%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Thrombosis
subjects affected / exposed	1 / 25 (4.00%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Peripheral ischaemia
subjects affected / exposed	1 / 25 (4.00%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Nervous system disorders
Haemorrhage intracranial
subjects affected / exposed	1 / 25 (4.00%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
subjects affected / exposed	1 / 25 (4.00%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Blood and lymphatic system disorders
Iron deficiency anaemia
subjects affected / exposed	1 / 25 (4.00%)
occurrences causally related to treatment / all	0 / 2
deaths causally related to treatment / all	0 / 0
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
subjects affected / exposed	1 / 25 (4.00%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Infections and infestations
Hepatitis C
subjects affected / exposed	1 / 25 (4.00%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Dengue fever
subjects affected / exposed	1 / 25 (4.00%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Metabolism and nutrition disorders
Hypocalcaemia
subjects affected / exposed	1 / 25 (4.00%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Octafibrin
Total subjects affected by non serious adverse events
subjects affected / exposed	7 / 25 (28.00%)
Injury, poisoning and procedural complications
Limb injury
subjects affected / exposed	3 / 25 (12.00%)
occurrences all number	3
Vascular disorders
Hypertension
subjects affected / exposed	2 / 25 (8.00%)
occurrences all number	2
Gastrointestinal disorders
Gingival bleeding
subjects affected / exposed	2 / 25 (8.00%)
occurrences all number	8
Vomiting
subjects affected / exposed	2 / 25 (8.00%)
occurrences all number	4
Skin and subcutaneous tissue disorders
Ecchymosis
subjects affected / exposed	2 / 25 (8.00%)
occurrences all number	4
Musculoskeletal and connective tissue disorders
Pain in extremity
subjects affected / exposed	3 / 25 (12.00%)
occurrences all number	4
Arthralgia
subjects affected / exposed	2 / 25 (8.00%)
occurrences all number	2

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

31 Oct 2014

Amendment 2: -More clearly definition of ‘subject observation and follow-up period,’ ‘treatment observation period,’ and ‘surgical observation period has been added. -Specification that the documentation of a bleeding episode extends across the entire ‘treatment observation period has been added. - Details for the time periods during which adverse events (AEs) and relevant concomitant medications are recorded have been added. - Details for the period of observation during which SAEs and relevant concomitant medications are documented have been added. - Further detail to the formula used to calculate the Octafibrin dose to be administered has been added.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Clinical trials

Clinical Trial Results:
Prospective, open-label, uncontrolled, Phase III study to assess the efficacy and safety of Octafibrin for on-demand treatment of acute bleeding and to prevent bleeding during and after surgery in subjects with congenital fibrinogen deficiency.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Haemostatic Efficacy in On-Demand Treatment of the First Bleeding Episode

Primary: Haemostatic Efficacy in On-Demand Treatment of the First Bleeding Episode

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: Prospective, open-label, uncontrolled, Phase III study to assess the efficacy and safety of Octafibrin for on-demand treatment of acute bleeding and to prevent bleeding during and after surgery in subjects with congenital fibrinogen deficiency.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Haemostatic Efficacy in On-Demand Treatment of the First Bleeding Episode

Primary: Haemostatic Efficacy in On-Demand Treatment of the First Bleeding Episode

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
Prospective, open-label, uncontrolled, Phase III study to assess the efficacy and safety of Octafibrin for on-demand treatment of acute bleeding and to prevent bleeding during and after surgery in subjects with congenital fibrinogen deficiency.