Trial Outcomes & Findings for Trial to Evaluate the Effect of Secondary Prophylaxis With rFVIII Therapy in Severe Hemophilia A Adult and/or Adolescent Subjects Compared to That of Episodic Treatment (NCT NCT00623480)
NCT ID: NCT00623480
Last Updated: 2014-11-17
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
84 participants
Primary outcome timeframe
After the last enrolled patient has been in the study for 1 year. At the cut-off, the median follow-up duration was 616 days (minimum was 111 days and maximum was 1109 days)
Results posted on
2014-11-17
Participant Flow
Participant milestones
| Measure |
Recombinant Factor VIII Prophylaxis Treatment
Participants received 25 IU/kg of Recombinant Factor VIII (Kogenate FS, BAY14-2222) intravenously (IV), 3 times per week. Dose escalation steps by 5 IU/kg (to 30 IU/kg or 35 IU/kg maximum) for patients exhibiting a bleeding frequency of 12 bleeding episodes per year or greater.
|
Recombinant Factor VIII On-demand Treatment
Participants received Recombinant Factor VIII (Kogenate FS, BAY14-2222) IV for bleeds in accordance with package insert instructions and study physician recommendations.
|
|---|---|---|
|
Overall Study
STARTED
|
42
|
42
|
|
Overall Study
COMPLETED
|
35
|
35
|
|
Overall Study
NOT COMPLETED
|
7
|
7
|
Reasons for withdrawal
| Measure |
Recombinant Factor VIII Prophylaxis Treatment
Participants received 25 IU/kg of Recombinant Factor VIII (Kogenate FS, BAY14-2222) intravenously (IV), 3 times per week. Dose escalation steps by 5 IU/kg (to 30 IU/kg or 35 IU/kg maximum) for patients exhibiting a bleeding frequency of 12 bleeding episodes per year or greater.
|
Recombinant Factor VIII On-demand Treatment
Participants received Recombinant Factor VIII (Kogenate FS, BAY14-2222) IV for bleeds in accordance with package insert instructions and study physician recommendations.
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
2
|
4
|
|
Overall Study
Lack of Efficacy
|
1
|
0
|
|
Overall Study
Non-compliant with study medication
|
4
|
0
|
|
Overall Study
Protocol Violation
|
0
|
1
|
|
Overall Study
Site closed by sponsor
|
0
|
1
|
Baseline Characteristics
Trial to Evaluate the Effect of Secondary Prophylaxis With rFVIII Therapy in Severe Hemophilia A Adult and/or Adolescent Subjects Compared to That of Episodic Treatment
Baseline characteristics by cohort
| Measure |
Recombinant Factor VIII Prophylaxis Treatment
n=42 Participants
Participants received 25 IU/kg of Recombinant Factor VIII (Kogenate FS, BAY14-2222) intravenously (IV), 3 times per week. Dose escalation steps by 5 IU/kg (to 30 IU/kg or 35 IU/kg maximum) for patients exhibiting a bleeding frequency of 12 bleeding episodes per year or greater.
|
Recombinant Factor VIII On-demand Treatment
n=42 Participants
Participants received Recombinant Factor VIII (Kogenate FS, BAY14-2222) IV for bleeds in accordance with package insert instructions and study physician recommendations.
|
Total
n=84 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
30.6 Years
STANDARD_DEVIATION 8.8 • n=93 Participants
|
30.7 Years
STANDARD_DEVIATION 9.7 • n=4 Participants
|
30.6 Years
STANDARD_DEVIATION 9.2 • n=27 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
42 Participants
n=93 Participants
|
42 Participants
n=4 Participants
|
84 Participants
n=27 Participants
|
|
Number of bleeds during last 6 months
|
10.0 Bleeds
STANDARD_DEVIATION 4.4 • n=93 Participants
|
12.2 Bleeds
STANDARD_DEVIATION 5.1 • n=4 Participants
|
11.1 Bleeds
STANDARD_DEVIATION 4.8 • n=27 Participants
|
|
Number of patients with target joints, Yes/No
Yes
|
28 Participants
n=93 Participants
|
31 Participants
n=4 Participants
|
59 Participants
n=27 Participants
|
|
Number of patients with target joints, Yes/No
No
|
14 Participants
n=93 Participants
|
11 Participants
n=4 Participants
|
25 Participants
n=27 Participants
|
PRIMARY outcome
Timeframe: After the last enrolled patient has been in the study for 1 year. At the cut-off, the median follow-up duration was 616 days (minimum was 111 days and maximum was 1109 days)Population: ITT (Intent-to-treat) Population
Outcome measures
| Measure |
Recombinant Factor VIII Prophylaxis Treatment
n=42 Participants
Participants received 25 IU/kg of Recombinant Factor VIII (Kogenate FS, BAY14-2222) intravenously (IV), 3 times per week. Dose escalation steps by 5 IU/kg (to 30 IU/kg or 35 IU/kg maximum) for patients exhibiting a bleeding frequency of 12 bleeding episodes per year or greater.
|
Recombinant Factor VIII On-demand Treatment
n=42 Participants
Participants received Recombinant Factor VIII (Kogenate FS, BAY14-2222) IV for bleeds in accordance with package insert instructions and study physician recommendations.
|
|---|---|---|
|
Bleeding Frequency (Number of Total Bleeds)
|
0 Bleeds
Interval 0.0 to 57.0
|
54.5 Bleeds
Interval 0.0 to 149.0
|
SECONDARY outcome
Timeframe: Baseline and 3 yearsPopulation: Full Analysis Set
The Extended MRI Scale total score has a range between 0 (normal unaffected joint) to 45 (maximal joint damage) points. It is composed of 2 domains, the soft tissue domain with a maximum of 9 points and the osteochondral domain with a maximum of 36 points. A single score for each subject was to be calculated from the sum of both domains and the average over all joints for the Extended MRI endpoint. Higher MRI score denotes greater joint structure damage thus a positive change from baseline means worsening.
Outcome measures
| Measure |
Recombinant Factor VIII Prophylaxis Treatment
n=41 Participants
Participants received 25 IU/kg of Recombinant Factor VIII (Kogenate FS, BAY14-2222) intravenously (IV), 3 times per week. Dose escalation steps by 5 IU/kg (to 30 IU/kg or 35 IU/kg maximum) for patients exhibiting a bleeding frequency of 12 bleeding episodes per year or greater.
|
Recombinant Factor VIII On-demand Treatment
n=38 Participants
Participants received Recombinant Factor VIII (Kogenate FS, BAY14-2222) IV for bleeds in accordance with package insert instructions and study physician recommendations.
|
|---|---|---|
|
Change From Baseline to 3 Years in the MRI (Magnetic Resonance Imaging) Scale.
|
0.79 Scores on a scale
Interval 0.27 to 1.32
|
0.96 Scores on a scale
Interval 0.34 to 1.58
|
SECONDARY outcome
Timeframe: Baseline and 3 yearsPopulation: Full Analysis Set
The total joint score is derived for each of six joints: left and right sides for knees (score: 0-25), ankles (score: 0-25), and elbows (score: 0-21). Higher CAJAS (Colorado Adult Joint Assessment Scale) score denotes greater joint structure damage thus a positive change from baseline means worsening. CAJAS total score is the sum of all 6 joints, ranging from 0 (best possible outcome) to 142 (worst possible outcome).
Outcome measures
| Measure |
Recombinant Factor VIII Prophylaxis Treatment
n=42 Participants
Participants received 25 IU/kg of Recombinant Factor VIII (Kogenate FS, BAY14-2222) intravenously (IV), 3 times per week. Dose escalation steps by 5 IU/kg (to 30 IU/kg or 35 IU/kg maximum) for patients exhibiting a bleeding frequency of 12 bleeding episodes per year or greater.
|
Recombinant Factor VIII On-demand Treatment
n=42 Participants
Participants received Recombinant Factor VIII (Kogenate FS, BAY14-2222) IV for bleeds in accordance with package insert instructions and study physician recommendations.
|
|---|---|---|
|
Change From Baseline to 3 Years in the Colorado Adult Joint Assessment Scale
|
-0.31 Scores on a scale
Interval -0.79 to 0.18
|
0.63 Scores on a scale
Interval 0.08 to 1.18
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline and 3 yearsPopulation: Full Analysis Set
The Haemo-QoL-A total score as well as each of its domains have a range between 0 (worst Quality of Life) and 100 (best Quality of Life) points. Therefore, a higher Haemo-QoL-A score denotes greater Quality of Life.
Outcome measures
| Measure |
Recombinant Factor VIII Prophylaxis Treatment
n=41 Participants
Participants received 25 IU/kg of Recombinant Factor VIII (Kogenate FS, BAY14-2222) intravenously (IV), 3 times per week. Dose escalation steps by 5 IU/kg (to 30 IU/kg or 35 IU/kg maximum) for patients exhibiting a bleeding frequency of 12 bleeding episodes per year or greater.
|
Recombinant Factor VIII On-demand Treatment
n=42 Participants
Participants received Recombinant Factor VIII (Kogenate FS, BAY14-2222) IV for bleeds in accordance with package insert instructions and study physician recommendations.
|
|---|---|---|
|
Change From Baseline to 3 Years in the Physical Functioning Domain of the Haemo-QoL-A
|
7.86 Scores on a scale
Interval 1.79 to 13.92
|
-5.30 Scores on a scale
Interval -11.97 to 1.37
|
Adverse Events
Recombinant Factor VIII Prophylaxis Treatment
Serious events: 9 serious events
Other events: 11 other events
Deaths: 0 deaths
Recombinant Factor VIII On-demand Treatment
Serious events: 11 serious events
Other events: 28 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Recombinant Factor VIII Prophylaxis Treatment
n=42 participants at risk
Participants received 25 IU/kg of Recombinant Factor VIII (Kogenate FS, BAY14-2222) intravenously (IV), 3 times per week. Dose escalation steps by 5 IU/kg (to 30 IU/kg or 35 IU/kg maximum) for patients exhibiting a bleeding frequency of 12 bleeding episodes per year or greater.
|
Recombinant Factor VIII On-demand Treatment
n=42 participants at risk
Participants received Recombinant Factor VIII (Kogenate FS, BAY14-2222) IV for bleeds in accordance with package insert instructions and study physician recommendations.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/42 • From randomization until Month 37.
|
2.4%
1/42 • Number of events 1 • From randomization until Month 37.
|
|
Congenital, familial and genetic disorders
Phimosis
|
0.00%
0/42 • From randomization until Month 37.
|
2.4%
1/42 • Number of events 1 • From randomization until Month 37.
|
|
Gastrointestinal disorders
Peritoneal haemorrhage
|
2.4%
1/42 • Number of events 1 • From randomization until Month 37.
|
0.00%
0/42 • From randomization until Month 37.
|
|
Gastrointestinal disorders
Retroperitoneal haematoma
|
2.4%
1/42 • Number of events 1 • From randomization until Month 37.
|
0.00%
0/42 • From randomization until Month 37.
|
|
Gastrointestinal disorders
Tooth impacted
|
2.4%
1/42 • Number of events 1 • From randomization until Month 37.
|
0.00%
0/42 • From randomization until Month 37.
|
|
Infections and infestations
Appendicitis
|
4.8%
2/42 • Number of events 2 • From randomization until Month 37.
|
2.4%
1/42 • Number of events 1 • From randomization until Month 37.
|
|
Infections and infestations
Device related infection
|
2.4%
1/42 • Number of events 1 • From randomization until Month 37.
|
0.00%
0/42 • From randomization until Month 37.
|
|
Infections and infestations
Peritonsillar abscess
|
2.4%
1/42 • Number of events 1 • From randomization until Month 37.
|
0.00%
0/42 • From randomization until Month 37.
|
|
Infections and infestations
Pilonidal cyst
|
2.4%
1/42 • Number of events 1 • From randomization until Month 37.
|
0.00%
0/42 • From randomization until Month 37.
|
|
Injury, poisoning and procedural complications
Fibula fracture
|
0.00%
0/42 • From randomization until Month 37.
|
2.4%
1/42 • Number of events 1 • From randomization until Month 37.
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.00%
0/42 • From randomization until Month 37.
|
2.4%
1/42 • Number of events 1 • From randomization until Month 37.
|
|
Injury, poisoning and procedural complications
Meniscus injury
|
2.4%
1/42 • Number of events 1 • From randomization until Month 37.
|
0.00%
0/42 • From randomization until Month 37.
|
|
Injury, poisoning and procedural complications
Stab wound
|
0.00%
0/42 • From randomization until Month 37.
|
2.4%
1/42 • Number of events 1 • From randomization until Month 37.
|
|
Injury, poisoning and procedural complications
Tibia fracture
|
0.00%
0/42 • From randomization until Month 37.
|
2.4%
1/42 • Number of events 1 • From randomization until Month 37.
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/42 • From randomization until Month 37.
|
2.4%
1/42 • Number of events 1 • From randomization until Month 37.
|
|
Musculoskeletal and connective tissue disorders
Haemarthrosis
|
0.00%
0/42 • From randomization until Month 37.
|
4.8%
2/42 • Number of events 2 • From randomization until Month 37.
|
|
Musculoskeletal and connective tissue disorders
Joint contracture
|
2.4%
1/42 • Number of events 1 • From randomization until Month 37.
|
0.00%
0/42 • From randomization until Month 37.
|
|
Musculoskeletal and connective tissue disorders
Joint lock
|
0.00%
0/42 • From randomization until Month 37.
|
2.4%
1/42 • Number of events 1 • From randomization until Month 37.
|
|
Musculoskeletal and connective tissue disorders
Joint range of motion decreased
|
0.00%
0/42 • From randomization until Month 37.
|
2.4%
1/42 • Number of events 1 • From randomization until Month 37.
|
|
Musculoskeletal and connective tissue disorders
Muscle haemorrhage
|
0.00%
0/42 • From randomization until Month 37.
|
2.4%
1/42 • Number of events 1 • From randomization until Month 37.
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/42 • From randomization until Month 37.
|
2.4%
1/42 • Number of events 1 • From randomization until Month 37.
|
|
Nervous system disorders
Migraine
|
2.4%
1/42 • Number of events 1 • From randomization until Month 37.
|
0.00%
0/42 • From randomization until Month 37.
|
|
Psychiatric disorders
Suicidal ideation
|
2.4%
1/42 • Number of events 1 • From randomization until Month 37.
|
0.00%
0/42 • From randomization until Month 37.
|
|
Reproductive system and breast disorders
Balanitis
|
0.00%
0/42 • From randomization until Month 37.
|
2.4%
1/42 • Number of events 1 • From randomization until Month 37.
|
|
Vascular disorders
Haematoma
|
2.4%
1/42 • Number of events 1 • From randomization until Month 37.
|
0.00%
0/42 • From randomization until Month 37.
|
Other adverse events
| Measure |
Recombinant Factor VIII Prophylaxis Treatment
n=42 participants at risk
Participants received 25 IU/kg of Recombinant Factor VIII (Kogenate FS, BAY14-2222) intravenously (IV), 3 times per week. Dose escalation steps by 5 IU/kg (to 30 IU/kg or 35 IU/kg maximum) for patients exhibiting a bleeding frequency of 12 bleeding episodes per year or greater.
|
Recombinant Factor VIII On-demand Treatment
n=42 participants at risk
Participants received Recombinant Factor VIII (Kogenate FS, BAY14-2222) IV for bleeds in accordance with package insert instructions and study physician recommendations.
|
|---|---|---|
|
Gastrointestinal disorders
Dental caries
|
0.00%
0/42 • From randomization until Month 37.
|
7.1%
3/42 • Number of events 3 • From randomization until Month 37.
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/42 • From randomization until Month 37.
|
7.1%
3/42 • Number of events 3 • From randomization until Month 37.
|
|
Gastrointestinal disorders
Toothache
|
7.1%
3/42 • Number of events 3 • From randomization until Month 37.
|
4.8%
2/42 • Number of events 3 • From randomization until Month 37.
|
|
General disorders
Pyrexia
|
2.4%
1/42 • Number of events 2 • From randomization until Month 37.
|
11.9%
5/42 • Number of events 6 • From randomization until Month 37.
|
|
Infections and infestations
Influenza
|
4.8%
2/42 • Number of events 2 • From randomization until Month 37.
|
16.7%
7/42 • Number of events 7 • From randomization until Month 37.
|
|
Infections and infestations
Nasopharyngitis
|
4.8%
2/42 • Number of events 2 • From randomization until Month 37.
|
16.7%
7/42 • Number of events 8 • From randomization until Month 37.
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/42 • From randomization until Month 37.
|
7.1%
3/42 • Number of events 4 • From randomization until Month 37.
|
|
Infections and infestations
Upper respiratory tract infection
|
2.4%
1/42 • Number of events 1 • From randomization until Month 37.
|
7.1%
3/42 • Number of events 5 • From randomization until Month 37.
|
|
Metabolism and nutrition disorders
Vitamin D deficiency
|
0.00%
0/42 • From randomization until Month 37.
|
7.1%
3/42 • Number of events 3 • From randomization until Month 37.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
11.9%
5/42 • Number of events 7 • From randomization until Month 37.
|
11.9%
5/42 • Number of events 6 • From randomization until Month 37.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/42 • From randomization until Month 37.
|
9.5%
4/42 • Number of events 5 • From randomization until Month 37.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
7.1%
3/42 • Number of events 3 • From randomization until Month 37.
|
2.4%
1/42 • Number of events 1 • From randomization until Month 37.
|
|
Nervous system disorders
Headache
|
4.8%
2/42 • Number of events 2 • From randomization until Month 37.
|
16.7%
7/42 • Number of events 12 • From randomization until Month 37.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/42 • From randomization until Month 37.
|
7.1%
3/42 • Number of events 3 • From randomization until Month 37.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/42 • From randomization until Month 37.
|
7.1%
3/42 • Number of events 3 • From randomization until Month 37.
|
|
Vascular disorders
Hypertension
|
0.00%
0/42 • From randomization until Month 37.
|
7.1%
3/42 • Number of events 3 • From randomization until Month 37.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Investigator must send a draft manuscript of the publication or abstract to the Sponsor sixty days in advance of submission in order to obtain written approval prior to submission of the final version for publication. In case of a difference of opinion between the Sponsor and the Investigator(s), the contents of the publication will be discussed in order to find a solution which satisfies both parties.
- Publication restrictions are in place
Restriction type: OTHER