Trial · NCT01181128
Study to Evaluate the Safety, Pharmacokinetics and Efficacy of Recombinant Factor VIII Fc Fusion Protein (rFVIIIFc) in Previously Treated Subjects With Severe Hemophilia A
NCT01181128, Phase 3, Completed, Bioverativ Therapeutics Inc.; results first posted 2014-08-29
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. Study to Evaluate the Safety, Pharmacokinetics and Efficacy of Recombinant Factor VIII Fc Fusion Protein (rFVIIIFc) in Previously Treated Subjects With Severe Hemophilia A. Trials, record NCT01181128. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT01181128
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- Study to Evaluate the Safety, Pharmacokinetics and Efficacy of Recombinant Factor VIII Fc Fusion Protein (rFVIIIFc) in Previously Treated Subjects With Severe Hemophilia A
- NCT number
- NCT01181128
- Status
- Completed
- Phases
- Phase 3
- Enrollment
- 165 participants, actual
- Lead sponsor
- Bioverativ Therapeutics Inc.
- Conditions
- Severe Hemophilia A
- Interventions
- Factor VIII (rFVIIIFc), Advate®
- First posted
- 2010-08-13
- Last updated
- 2021-01-08
- Results first posted
- 2014-08-29
Source ClinicalTrials.gov
Registered outcomes40
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Incidence Rate of FVIII Inhibitor Development | up to 52 weeks ± 2 weeks | An inhibitor test result ≥0.6 Bethesda units (BU)/mL, identified and confirmed by re-testing of a second sample obtained within 2 to 4 weeks, was considered positive. Both tests were to be performed using the Nijmegen-modified Bethesda Assay by the central laboratory. The incidence rates along with the 95% confidence interval (CI) were summarized for all titers for subjects with 50 or more exposure days (EDs) to rFVIIIFc and a valid inhibitor test after the 50th exposure. In addition, the incidence rates for all subjects regardless of their exposure days to rFVIIIFc were also summarized. The 95% CI was calculated using Clopper-Pearson exact method. |
| Primary | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | up to 52 weeks + 30 days ± 1 week | AE=any untoward medical occurrence that did not necessarily have a causal relationship with treatment, and could be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study product, whether related or not. TEAE=AE present prior to receiving the first injection of Advate or rFVIIIFc that subsequently worsened in severity or not present prior to receiving the first injection but subsequently appeared before the last visit on study. Serious AE (SAE)=AE resulting in death, immediate risk of death, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, or a congenital anomaly/birth defect, or any other medically important event. AEs emergent between the first Advate injection and first on-study rFVIIIFc injection (Sequential PK Subgroup) or during the surgical/rehabilitation period (Surgery Subgroup) are presented separately. |
| Primary | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values From Baseline | up to 52 weeks ± 2 weeks | Clinical laboratory evaluations included hematology and blood chemistry. Table does not include laboratory tests evaluated during the surgical/rehabilitation period. ULN=upper limit of normal. |
| Primary | Number of Participants With Clinically Relevant Abnormalities in Vital Signs or Relevant Changes From Baseline in Vital Signs | up to 52 weeks ± 2 weeks | Number of participants with clinically relevant abnormalities or relevant changes from baseline in temperature, pulse (beats per minute \[bpm\]), systolic blood pressure (SBP), and diastolic blood pressure (DBP) are presented. Baseline (BL) is defined as the last non-missing evaluable assessment taken prior and closest to the first rFVIIIFc dose. ↑ signifies increase and ↓ signifies decrease. |
| Primary | Annualized Bleeding Rate | up to 52 weeks ± 2 weeks (efficacy period as defined in description) | Annualized bleeding episodes = (number of bleeding episodes during the efficacy period / number of days during the efficacy period)\*365.25. The efficacy period in Arms 1 and 2 began with the first prophylactic dose of rFVIIIFc and ended with the last dose (regardless of reason for dosing). The efficacy period in Arm 3 began at the time of last PK rFVIIIFc sampling timepoint and ended at the date of the last study visit. Periods of PK evaluations and surgery/rehabilitation are not included in the efficacy period. A bleeding episode started from the first sign of a bleed, and ended 72 hours after the last treatment for the bleeding, within which any symptoms of bleeding at the same location, or injections less than or equal to 72 hours apart, were considered the same bleeding episode. |
| Primary | Comparison of Annualized Bleeding Rates: Arm 1 Versus Arm 3 | up to 52 weeks ± 2 weeks (efficacy period as defined in description) | Estimated using the negative binomial model with treatment arm as covariate, based on whole study duration for all participants. Annualized bleeding episodes = (number of bleeding episodes / number of days in the respective period)\*365.25.The efficacy period in Arm 1 began with the first prophylactic dose of rFVIIIFc and ended with the last dose (regardless of reason for dosing). The efficacy period in Arm 3 began at the time of last PK rFVIIIFc sampling timepoint and ended at the date of the last study visit. Periods of PK evaluations and surgery/rehabilitation are not included in the efficacy period. A bleeding episode started from the first sign of a bleed, and ended 72 hours after the last treatment for the bleeding, within which any symptoms of bleeding at the same location, or injections less than or equal to 72 hours apart, were considered part of the same bleeding episode. |
| Primary | Area Under the Curve (AUC) Per Dose (One-stage Clotting Assay) | See Measure Description for complete time frame. | Dose normalized area under the drug concentration-time curve. Sampling for Advate PK profiling was conducted, following at least 96 hours of washout, at these timepoints: preinjection and at either 30 (±3) minutes or 10 (±3) minutes, 1 hour (±15 minutes), 6 (±1) hours, 24 (±2) hours (Day 1), 48 (±2) hours (Day 2), and 72 (±2) hours (Day 3) from the start of the injection. Sampling for rFVIIIFc PK profiling was conducted at Day 0 (directly following at least 96 hours washout from Advate PK profiling or within 4 weeks of the Advate dose or other rFVIII product) and repeated 12 to 24 weeks later at the following timepoints: preinjection and at 30 (±3) minutes (or 10 (±3) minutes), 1 hour (±15 minutes), 6 (±1) hours, 24 (±2) hours (Day 1), 72 (±2) hours (Day 3), 96 (±2) hours (Day 4), and 120 (±2) hours (Day 5) from the start of the injection. |
| Primary | Elimination Half Life (t1/2; One-stage Clotting Assay) | See Measure Description for complete time frame. | Time required for the activity of the drug to reach half of its original value. Sampling for Advate PK profiling was conducted, following at least 96 hours of washout, at these timepoints: preinjection and at either 30 (±3) minutes or 10 (±3) minutes, 1 hour (±15 minutes), 6 (±1) hours, 24 (±2) hours (Day 1), 48 (±2) hours (Day 2), and 72 (±2) hours (Day 3) from the start of the injection. Sampling for rFVIIIFc PK profiling was conducted at Day 0 (directly following at least 96 hours washout from Advate PK profiling or within 4 weeks of the Advate dose or other rFVIII product) and repeated 12 to 24 weeks later at the following timepoints: preinjection and at 30 (±3) minutes (or 10 (±3) minutes), 1 hour (±15 minutes), 6 (±1) hours, 24 (±2) hours (Day 1), 72 (±2) hours (Day 3), 96 (±2) hours (Day 4), and 120 (±2) hours (Day 5) from the start of the injection. |
| Primary | Clearance (CL; One-stage Clotting Assay) | See Measure Description for complete time frame. | Rate at which the body removes the drug, measured as the volume of the plasma cleared of drug per unit time per unit weight. Sampling for Advate PK profiling was conducted, following at least 96 hours of washout, at these timepoints: preinjection and at either 30 (±3) minutes or 10 (±3) minutes, 1 hour (±15 minutes), 6 (±1) hours, 24 (±2) hours (Day 1), 48 (±2) hours (Day 2), and 72 (±2) hours (Day 3) from the start of the injection. Sampling for rFVIIIFc PK profiling was conducted at Day 0 (directly following at least 96 hours washout from Advate PK profiling or within 4 weeks of the Advate dose or other rFVIII product) and repeated 12 to 24 weeks later at the following timepoints: preinjection and at 30 (±3) minutes (or 10 (±3) minutes), 1 hour (±15 minutes), 6 (±1) hours, 24 (±2) hours (Day 1), 72 (±2) hours (Day 3), 96 (±2) hours (Day 4), and 120 (±2) hours (Day 5) from the start of the injection. |
| Primary | Mean Residence Time (MRT; One-stage Clotting Assay) | See Measure Description for complete time frame. | The average time that a drug molecule is present in the systemic circulation. Sampling for Advate PK profiling was conducted, following at least 96 hours of washout, at these timepoints: preinjection and at either 30 (±3) minutes or 10 (±3) minutes, 1 hour (±15 minutes), 6 (±1) hours, 24 (±2) hours (Day 1), 48 (±2) hours (Day 2), and 72 (±2) hours (Day 3) from the start of the injection. Sampling for rFVIIIFc PK profiling was conducted at Day 0 (directly following at least 96 hours washout from Advate PK profiling or within 4 weeks of the Advate dose or other rFVIII product) and repeated 12 to 24 weeks later at the following timepoints: preinjection and at 30 (±3) minutes (or 10 (±3) minutes), 1 hour (±15 minutes), 6 (±1) hours, 24 (±2) hours (Day 1), 72 (±2) hours (Day 3), 96 (±2) hours (Day 4), and 120 (±2) hours (Day 5) from the start of the injection. |
1 to 10 of 40Source ClinicalTrials.gov
See all 40 registered outcomesOutcomes40
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Incidence Rate of FVIII Inhibitor Development | up to 52 weeks ± 2 weeks | Safety Analysis Set: participants who received at least 1 dose of Advate or at least 1 dose of rFVIIIFc; n=number of participants with given number of exposure days who had a valid inhibitor test. | percentage of participants | NUMBER |
| PRIMARY | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | up to 52 weeks + 30 days ± 1 week | Safety Analysis Set: participants who received at least 1 dose of Advate or at least 1 dose of rFVIIIFc. For Arm 1, AEs emergent between 1st on-study Advate dose and 1st rFVIIIFc dose are reported as treatment-emergent to Advate (1st column); AEs emergent after 1st rFVIIIFc injection are reported as treatment-emergent to rFVIIIFc (2nd column). | participants | NUMBER |
| PRIMARY | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values From Baseline | up to 52 weeks ± 2 weeks | Safety Analysis Set: participants who received at least 1 dose of Advate or at least 1 dose of rFVIIIFc n=the number of participants with at least one post-baseline value. | participants | NUMBER |
| PRIMARY | Number of Participants With Clinically Relevant Abnormalities in Vital Signs or Relevant Changes From Baseline in Vital Signs | up to 52 weeks ± 2 weeks | Safety Analysis Set: participants who received at least 1 dose of Advate or at least 1 dose of rFVIIIFc and had a baseline assessment and at least one post-baseline assessment for temperature or at least one post-baseline assessment for pulse, systolic blood pressure, and diastolic blood pressure. | participants | NUMBER |
| PRIMARY | Annualized Bleeding Rate | up to 52 weeks ± 2 weeks (efficacy period as defined in description) | Full Analysis Set: participants who received at least 1 dose of rFVIIIFc with an efficacy assessment. | episodes per participant per year | MEDIAN |
| PRIMARY | Comparison of Annualized Bleeding Rates: Arm 1 Versus Arm 3 | up to 52 weeks ± 2 weeks (efficacy period as defined in description) | Full Analysis Set: participants who received at least 1 dose of rFVIIIFc with an efficacy assessment. | episodes per participant per year | NUMBER |
| PRIMARY | Area Under the Curve (AUC) Per Dose (One-stage Clotting Assay) | See Measure Description for complete time frame. | Participants who had evaluable one-stage PK profiles for both Advate and baseline rFVIIIFc. | IU*h/dL per IU/kg | GEOMETRIC_MEAN |
| PRIMARY | Elimination Half Life (t1/2; One-stage Clotting Assay) | See Measure Description for complete time frame. | Participants who had evaluable one-stage PK profiles for both Advate and baseline rFVIIIFc. | hours | GEOMETRIC_MEAN |
| PRIMARY | Clearance (CL; One-stage Clotting Assay) | See Measure Description for complete time frame. | Participants who had evaluable one-stage PK profiles for both Advate and baseline rFVIIIFc. | mL/h/kg | GEOMETRIC_MEAN |
| PRIMARY | Mean Residence Time (MRT; One-stage Clotting Assay) | See Measure Description for complete time frame. | Participants who had evaluable one-stage PK profiles for both Advate and baseline rFVIIIFc. | hours | GEOMETRIC_MEAN |
1 to 10 of 40Source ClinicalTrials.gov
See all 40 outcomesResults by group392
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Incidence Rate of FVIII Inhibitor Development | Arm 1: Individualized (Tailored) Prophylaxis | Participants with>=50 EDs; n=107, 1, 2, 110 | 0 | 95% Confidence Interval 0.0 to 3.4 | percentage of participants |
| Incidence Rate of FVIII Inhibitor Development | Arm 2: Weekly Prophylaxis | Participants with>=50 EDs; n=107, 1, 2, 110 | 0 | 95% Confidence Interval 0.0 to 97.5 | percentage of participants |
| Incidence Rate of FVIII Inhibitor Development | Arm 3: Episodic (On-Demand) Dosing | Participants with>=50 EDs; n=107, 1, 2, 110 | 0 | 95% Confidence Interval 0.0 to 84.2 | percentage of participants |
| Incidence Rate of FVIII Inhibitor Development | All Arms: Total | Participants with>=50 EDs; n=107, 1, 2, 110 | 0 | 95% Confidence Interval 0.0 to 3.3 | percentage of participants |
| Incidence Rate of FVIII Inhibitor Development | Arm 1: Individualized (Tailored) Prophylaxis | All participants; n=117, 24, 23, 164 | 0 | 95% Confidence Interval 0.0 to 3.1 | percentage of participants |
| Incidence Rate of FVIII Inhibitor Development | Arm 2: Weekly Prophylaxis | All participants; n=117, 24, 23, 164 | 0 | 95% Confidence Interval 0.0 to 14.2 | percentage of participants |
| Incidence Rate of FVIII Inhibitor Development | Arm 3: Episodic (On-Demand) Dosing | All participants; n=117, 24, 23, 164 | 0 | 95% Confidence Interval 0.0 to 14.8 | percentage of participants |
| Incidence Rate of FVIII Inhibitor Development | All Arms: Total | All participants; n=117, 24, 23, 164 | 0 | 95% Confidence Interval 0.0 to 2.2 | percentage of participants |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | Arm 1: Individualized (Tailored) Prophylaxis, Advate | >=1 TEAE | 3 | participants | |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | Arm 1: Individualized (Tailored) Prophylaxis, rFVIIIFc Only | >=1 TEAE | 80 | participants |
1 to 10 of 392Source ClinicalTrials.gov
See all 392 results by groupParticipant flow15
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Overall Study | STARTED | Arm 1: Individualized (Tailored) Prophylaxis | 118 | |
| Overall Study | STARTED | Arm 2: Weekly Prophylaxis | 24 | |
| Overall Study | STARTED | Arm 3: Episodic (On-Demand) Dosing | 23 | |
| Overall Study | Pharmacokinetic (PK) Subgroup | Arm 1: Individualized (Tailored) Prophylaxis | 30 | |
| Overall Study | Pharmacokinetic (PK) Subgroup | Arm 2: Weekly Prophylaxis | 0 | |
| Overall Study | Pharmacokinetic (PK) Subgroup | Arm 3: Episodic (On-Demand) Dosing | 0 | |
| Overall Study | Perioperative Management Subgroup | Arm 1: Individualized (Tailored) Prophylaxis | 8 | |
| Overall Study | Perioperative Management Subgroup | Arm 2: Weekly Prophylaxis | 1 | |
| Overall Study | Perioperative Management Subgroup | Arm 3: Episodic (On-Demand) Dosing | 0 | |
| Overall Study | COMPLETED | Arm 1: Individualized (Tailored) Prophylaxis | 112 |
1 to 10 of 15Source ClinicalTrials.gov
See all 15 participant flowAdverse events60
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Nasopharyngitis | Infections and infestations | Individualized (Tailored) Prophylaxis, rFVIIIFc | 16 | 117 | |
| other | Nasopharyngitis | Infections and infestations | Weekly Prophylaxis | 1 | 24 | |
| other | Nasopharyngitis | Infections and infestations | Episodic (On-Demand) Dosing | 3 | 23 | |
| other | Upper respiratory tract infection | Infections and infestations | Individualized (Tailored) Prophylaxis, rFVIIIFc | 6 | 117 | |
| other | Upper respiratory tract infection | Infections and infestations | Weekly Prophylaxis | 0 | 24 | |
| other | Upper respiratory tract infection | Infections and infestations | Episodic (On-Demand) Dosing | 3 | 23 | |
| other | Arthralgia | Musculoskeletal and connective tissue disorders | Individualized (Tailored) Prophylaxis, rFVIIIFc | 10 | 117 | |
| other | Arthralgia | Musculoskeletal and connective tissue disorders | Weekly Prophylaxis | 2 | 24 | |
| other | Arthralgia | Musculoskeletal and connective tissue disorders | Episodic (On-Demand) Dosing | 1 | 23 | |
| other | Headache | Nervous system disorders | Individualized (Tailored) Prophylaxis, rFVIIIFc | 5 | 117 |
1 to 10 of 60Source ClinicalTrials.gov
See all 60 adverse eventsAdverse event totals9
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Individualized (Tailored) Prophylaxis, rFVIIIFc | ||
| Total, all-cause mortality | Weekly Prophylaxis | ||
| Total, all-cause mortality | Episodic (On-Demand) Dosing | ||
| Total, other adverse events | Individualized (Tailored) Prophylaxis, rFVIIIFc | 32 | 117 |
| Total, other adverse events | Weekly Prophylaxis | 8 | 24 |
| Total, other adverse events | Episodic (On-Demand) Dosing | 7 | 23 |
| Total, serious adverse events | Individualized (Tailored) Prophylaxis, rFVIIIFc | 10 | 117 |
| Total, serious adverse events | Weekly Prophylaxis | 2 | 24 |
| Total, serious adverse events | Episodic (On-Demand) Dosing | 0 | 23 |
Source ClinicalTrials.gov
Papers4
The papers the trial lists on ClinicalTrials.gov.
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons0
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
None in this release.
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
For software
Read this trial from software.
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