Trial Outcomes & Findings for Study to Investigate Immunogenicity, Efficacy and Safety of Treatment With Human-cl rhFVIII (NCT NCT01992549)
NCT ID: NCT01992549
Last Updated: 2021-01-19
Results Overview
The number of patients developing FVIII inhibitors was observed during the observation period by assessing inhibitor development by the modified Bethesda assay (Nijmegen modification) using congenital FVIII-deficient human plasma spiked with Human-cl rhFVIII. The definition threshold for a "positive" inhibitor was if the modified Bethesda assay resulted in a titre ≥0.6 BU/mL at any time point during the observation period.
COMPLETED
PHASE3
48 participants
Maximum two years
2021-01-19
Participant Flow
Participant milestones
| Measure |
Human-cl rhFVIII
Of the total number of patients that started in the study, all those in the safety (SAF) population received at least 1 infusion of Human-cl rhFVIII. Patients who had data collected post-treatment were included in the intent-to-treat (ITT) population. Prophylactic treatment dose given to all patients in the PROPH population (all patients who received at least 1 administration of Human-cl rhFVIII with prophylaxis documented as the reason for treatment): \>20 IU FVIII/kg body weight (BW). On-demand treatment of bleeding episodes (BEs) dose given to the BLEED population (all patients with bleeding episodes treated with Human-cl rhFVIII): 20-30 IU FVIII/kg BW (minor haemorrhage), 30-40 IU FVIII/kg BW (moderate to major haemorrhage) or 50-80 IU FVIII/kg BW (major to life-threatening haemorrhage). Surgical prophylaxis dose was given to the SURG population (all patients with surgeries treated with Human-cl rhFVIII): 25-30 IU FVIII/kg BW (minor surgeries); \>50 IU FVIII/kg BW (major surgeries).
|
|---|---|
|
Overall Study
STARTED
|
48
|
|
Overall Study
SAF Population
|
48
|
|
Overall Study
ITT Population
|
47
|
|
Overall Study
PROPH Population
|
47
|
|
Overall Study
BLEED Population
|
29
|
|
Overall Study
SURG Population
|
3
|
|
Overall Study
COMPLETED
|
44
|
|
Overall Study
NOT COMPLETED
|
4
|
Reasons for withdrawal
| Measure |
Human-cl rhFVIII
Of the total number of patients that started in the study, all those in the safety (SAF) population received at least 1 infusion of Human-cl rhFVIII. Patients who had data collected post-treatment were included in the intent-to-treat (ITT) population. Prophylactic treatment dose given to all patients in the PROPH population (all patients who received at least 1 administration of Human-cl rhFVIII with prophylaxis documented as the reason for treatment): \>20 IU FVIII/kg body weight (BW). On-demand treatment of bleeding episodes (BEs) dose given to the BLEED population (all patients with bleeding episodes treated with Human-cl rhFVIII): 20-30 IU FVIII/kg BW (minor haemorrhage), 30-40 IU FVIII/kg BW (moderate to major haemorrhage) or 50-80 IU FVIII/kg BW (major to life-threatening haemorrhage). Surgical prophylaxis dose was given to the SURG population (all patients with surgeries treated with Human-cl rhFVIII): 25-30 IU FVIII/kg BW (minor surgeries); \>50 IU FVIII/kg BW (major surgeries).
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|---|---|
|
Overall Study
Lost to Follow-up
|
2
|
|
Overall Study
Serious Adverse Event
|
1
|
|
Overall Study
Product Switch to Extend Half Life
|
1
|
Baseline Characteristics
Study to Investigate Immunogenicity, Efficacy and Safety of Treatment With Human-cl rhFVIII
Baseline characteristics by cohort
| Measure |
Human-cl rhFVIII
n=48 Participants
The safety (SAF) population consist of all patients who received at least one infusion of Human-cl rhFVIII (n=48).
|
|---|---|
|
Age, Continuous
|
3.47 Years
STANDARD_DEVIATION 2.13 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
48 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
48 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
9 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
36 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Body Mass Index (BMI) at screening
|
16.46 kg/m^2
n=5 Participants
|
|
Height at screening
|
97.44 Centimeters (cm)
n=5 Participants
|
|
Weight at screening
|
15.84 Kilograms (kg)
n=5 Participants
|
|
Family history of inhibitors
Yes
|
3 Participants
n=5 Participants
|
|
Family history of inhibitors
No
|
45 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Maximum two yearsPopulation: The analysis was performed for the safety (SAF) population which includes all patients who received at least 1 infusion of Human-cl rhFVIII (N=48)
The number of patients developing FVIII inhibitors was observed during the observation period by assessing inhibitor development by the modified Bethesda assay (Nijmegen modification) using congenital FVIII-deficient human plasma spiked with Human-cl rhFVIII. The definition threshold for a "positive" inhibitor was if the modified Bethesda assay resulted in a titre ≥0.6 BU/mL at any time point during the observation period.
Outcome measures
| Measure |
Human-cl rhFVIII
n=48 Participants
The safety (SAF) population consist of all patients who received at least one infusion of Human-cl rhFVIII
|
Major Surgeries
All patients that had major surgeries performed under Human-cl rhFVIII treatment (n=2)
|
SURG Population
All patients that had surgeries performed under Human-cl rhFVIII treatment (n=3)
|
|---|---|---|---|
|
Immunogenicity of Human-cl rhFVIII: Incidence of Inhibitors
|
0 participants
Interval 0.0 to 7.549
|
—
|
—
|
SECONDARY outcome
Timeframe: Maximum 2 yearsPopulation: The analysis population includes all patients in PROPH population who received at least one prophylactic treatment with Human-cl rhFVIII (n=47).
The annualized bleeding rate (ABR) was calculated during the time of prophylactic treatment with Human-cl rhFVIII for spontaneous bleeding events (BEs).
Outcome measures
| Measure |
Human-cl rhFVIII
n=47 Participants
The safety (SAF) population consist of all patients who received at least one infusion of Human-cl rhFVIII
|
Major Surgeries
All patients that had major surgeries performed under Human-cl rhFVIII treatment (n=2)
|
SURG Population
All patients that had surgeries performed under Human-cl rhFVIII treatment (n=3)
|
|---|---|---|---|
|
Frequency of Spontaneous Break-through Bleeds
|
0.283 Events/year (ABR)
Interval 0.153 to 0.527
|
—
|
—
|
SECONDARY outcome
Timeframe: Maximum 2 yearsPopulation: The analysis population included all patients who received on-demand treatment with Human-cl rhFVIII for bleeding episodes (BLEED population; n=29).
A personal efficacy assessment (final outcome) to assess the efficacy of Human-cl rhFVIII for the on-demand treatment of bleeding episodes (BEs) at the end of a BE. Efficacy was assessed using a four-point scale (excellent, good, moderate, none) by the patient's parent(s)/legal guardian(s) together with the investigator in case of on site treatment.
Outcome measures
| Measure |
Human-cl rhFVIII
n=111 Bleeding episodes
The safety (SAF) population consist of all patients who received at least one infusion of Human-cl rhFVIII
|
Major Surgeries
All patients that had major surgeries performed under Human-cl rhFVIII treatment (n=2)
|
SURG Population
All patients that had surgeries performed under Human-cl rhFVIII treatment (n=3)
|
|---|---|---|---|
|
Efficacy of Human-cl rhFVIII for the Treatment of Bleeds
Excellent
|
58 Bleeding episodes
|
—
|
—
|
|
Efficacy of Human-cl rhFVIII for the Treatment of Bleeds
Good
|
28 Bleeding episodes
|
—
|
—
|
|
Efficacy of Human-cl rhFVIII for the Treatment of Bleeds
Moderate
|
21 Bleeding episodes
|
—
|
—
|
|
Efficacy of Human-cl rhFVIII for the Treatment of Bleeds
None
|
3 Bleeding episodes
|
—
|
—
|
|
Efficacy of Human-cl rhFVIII for the Treatment of Bleeds
Not done
|
1 Bleeding episodes
|
—
|
—
|
SECONDARY outcome
Timeframe: Maximum 2 yearsPopulation: The analysis population includes 3 patients that received Human-cl rhFVIII for surgical prophylaxis during a total of 4 surgeries (SURG population). Of these, 1 patient had two minor surgeries and 2 patients had one major surgery each.
An overall efficacy assessment to assess the efficacy of human-cl rhFVIII in surgical prophylaxis of minor and major surgeries. The efficacy assessment was analyzed using a four-point scale (excellent, good, moderate, none). If surgeries could not be assessed due to limited data available or having taken place outside the study site, the results were classified as "not done".
Outcome measures
| Measure |
Human-cl rhFVIII
n=2 Surgeries
The safety (SAF) population consist of all patients who received at least one infusion of Human-cl rhFVIII
|
Major Surgeries
n=2 Surgeries
All patients that had major surgeries performed under Human-cl rhFVIII treatment (n=2)
|
SURG Population
n=4 Surgeries
All patients that had surgeries performed under Human-cl rhFVIII treatment (n=3)
|
|---|---|---|---|
|
Efficacy of Human-cl rhFVIII for Surgical Prophylaxis
Good
|
0 Surgeries
|
0 Surgeries
|
0 Surgeries
|
|
Efficacy of Human-cl rhFVIII for Surgical Prophylaxis
Not done
|
2 Surgeries
|
0 Surgeries
|
2 Surgeries
|
|
Efficacy of Human-cl rhFVIII for Surgical Prophylaxis
Excellent
|
0 Surgeries
|
2 Surgeries
|
2 Surgeries
|
|
Efficacy of Human-cl rhFVIII for Surgical Prophylaxis
Moderate
|
0 Surgeries
|
0 Surgeries
|
0 Surgeries
|
|
Efficacy of Human-cl rhFVIII for Surgical Prophylaxis
None
|
0 Surgeries
|
0 Surgeries
|
0 Surgeries
|
SECONDARY outcome
Timeframe: Maximum 2 yearsPopulation: The analysis was performed for the safety (SAF) population which includes all patients who received at least 1 infusion of Human-cl rhFVIII (n=48).
The frequency of AEs, as monitored throughout the whole study by the number of patients with at least one adverse event occurrence.
Outcome measures
| Measure |
Human-cl rhFVIII
n=48 Participants
The safety (SAF) population consist of all patients who received at least one infusion of Human-cl rhFVIII
|
Major Surgeries
All patients that had major surgeries performed under Human-cl rhFVIII treatment (n=2)
|
SURG Population
All patients that had surgeries performed under Human-cl rhFVIII treatment (n=3)
|
|---|---|---|---|
|
The Occurrence of Any Adverse Event (AE)
Adverse event
|
29 Participants
|
—
|
—
|
|
The Occurrence of Any Adverse Event (AE)
Serious adverse event (SAE)
|
5 Participants
|
—
|
—
|
|
The Occurrence of Any Adverse Event (AE)
Severe AE
|
3 Participants
|
—
|
—
|
|
The Occurrence of Any Adverse Event (AE)
Temporally related adverse event
|
20 Participants
|
—
|
—
|
|
The Occurrence of Any Adverse Event (AE)
Death
|
0 Participants
|
—
|
—
|
|
The Occurrence of Any Adverse Event (AE)
AE leading to permanent discontinuation
|
1 Participants
|
—
|
—
|
Adverse Events
SAF Population
Serious adverse events
| Measure |
SAF Population
n=48 participants at risk
The safety (SAF) population consist of all patients who received at least one infusion of Human-cl rhFVIII (n=48).
|
|---|---|
|
Infections and infestations
Pneumonia
|
4.2%
2/48 • Maximum 2 years
|
|
Infections and infestations
Varicella
|
2.1%
1/48 • Maximum 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
2.1%
1/48 • Maximum 2 years
|
|
Vascular disorders
Haemorrhage
|
2.1%
1/48 • Maximum 2 years
|
|
Gastrointestinal disorders
Gastritis
|
2.1%
1/48 • Maximum 2 years
|
|
Infections and infestations
Cellulitis
|
2.1%
1/48 • Maximum 2 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neuroblastoma
|
2.1%
1/48 • Maximum 2 years
|
Other adverse events
| Measure |
SAF Population
n=48 participants at risk
The safety (SAF) population consist of all patients who received at least one infusion of Human-cl rhFVIII (n=48).
|
|---|---|
|
Infections and infestations
Nasopharyngitis
|
20.8%
10/48 • Maximum 2 years
|
|
Infections and infestations
Varicella
|
10.4%
5/48 • Maximum 2 years
|
|
Infections and infestations
Bronchitis
|
8.3%
4/48 • Maximum 2 years
|
|
Infections and infestations
Ear infection
|
8.3%
4/48 • Maximum 2 years
|
|
Infections and infestations
Pharyngitis
|
8.3%
4/48 • Maximum 2 years
|
|
Infections and infestations
Tonsillitis
|
6.2%
3/48 • Maximum 2 years
|
|
Infections and infestations
Otitis media
|
4.2%
2/48 • Maximum 2 years
|
|
Infections and infestations
Pneumonia
|
4.2%
2/48 • Maximum 2 years
|
|
Infections and infestations
Pulpitis dental
|
4.2%
2/48 • Maximum 2 years
|
|
Infections and infestations
Respiratory tract infection viral
|
4.2%
2/48 • Maximum 2 years
|
|
Infections and infestations
Tracheitis
|
4.2%
2/48 • Maximum 2 years
|
|
General disorders
Pyrexia
|
20.8%
10/48 • Maximum 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
14.6%
7/48 • Maximum 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
4.2%
2/48 • Maximum 2 years
|
|
Gastrointestinal disorders
Diarrhoea
|
4.2%
2/48 • Maximum 2 years
|
|
Gastrointestinal disorders
Vomiting
|
4.2%
2/48 • Maximum 2 years
|
|
Blood and lymphatic system disorders
Anaemia
|
8.3%
4/48 • Maximum 2 years
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Octapharma agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Octapharma supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial. Octapharma also reserves the right to review data prior to publishing and provide comments/changes within a certain time period.
- Publication restrictions are in place
Restriction type: OTHER