Trial Outcomes & Findings for Study of PF-05208756, Moroctocog Alfa (AF-CC), Xyntha For Male Chinese Subjects With Hemophilia A (NCT NCT02461992)

NCT ID: NCT02461992

Last Updated: 2016-09-07

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 13 participants
• Primary outcome timeframe: Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose
• Results posted on: 2016-09-07

Participant Flow

This study recruited Chinese male participants that were age 6 years or older with severe hemophilia A (factor VIII [FVIII] activity <1%) previously treated with >150 exposure days to any FVIII-containing product.

Participant milestones

Measure	Xyntha 50 IU/kg Participants were administered a single dose of recombinant antihemophilic factor (Xyntha) at 50 international units per kilogram (IU/kg) infused intravenously over 10 minutes.
Overall Study STARTED	13
Overall Study COMPLETED	13
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study of PF-05208756, Moroctocog Alfa (AF-CC), Xyntha For Male Chinese Subjects With Hemophilia A

Baseline characteristics by cohort

Measure	Xyntha 50 IU/kg n=13 Participants Participants were administered a single dose of recombinant antihemophilic factor (Xyntha) at 50 international units per kilogram (IU/kg) infused intravenously over 10 minutes.
Age, Customized 6 to 11 years	3 participants 19.6 • n=93 Participants
Age, Customized 12 to 17 years	5 participants n=93 Participants
Age, Customized 18 to 44 years	2 participants n=93 Participants
Age, Customized 45 to 64 years	3 participants n=93 Participants
Age, Customized Greater than or equal to 65 years	0 participants n=93 Participants
Sex: Female, Male Female	0 Participants n=93 Participants
Sex: Female, Male Male	13 Participants n=93 Participants

PRIMARY outcome

Timeframe: Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose

Population: The pharmacokinetic (PK) parameter analysis population is defined as all participants enrolled and treated who have at least 1 of the PK parameters of primary interest reported.

Outcome measures

Measure	Xyntha 50 IU/kg n=13 Participants Participants were administered a single dose of recombinant antihemophilic factor (Xyntha) at 50 international units per kilogram (IU/kg) infused intravenously over 10 minutes.
Maximum Plasma FVIII Activity (Cmax)	1.147 IU/milliliter (mL) Geometric Coefficient of Variation 44

PRIMARY outcome

Timeframe: Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose

Population: The PK parameter analysis population is defined as all participants enrolled and treated who have at least 1 of the PK parameters of primary interest reported.

Outcome measures

Measure	Xyntha 50 IU/kg n=13 Participants Participants were administered a single dose of recombinant antihemophilic factor (Xyntha) at 50 international units per kilogram (IU/kg) infused intravenously over 10 minutes.
Area Under the Plasma FVIII Activity-Time Profile From Time 0 to Time of the Last Quantifiable Concentration (AUClast)	14.49 IU*hour/mL Geometric Coefficient of Variation 57

PRIMARY outcome

Timeframe: Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose

Population: The PK parameter analysis population is defined as all participants enrolled and treated who have at least 1 of the PK parameters of primary interest reported.

Outcome measures

Measure	Xyntha 50 IU/kg n=13 Participants Participants were administered a single dose of recombinant antihemophilic factor (Xyntha) at 50 international units per kilogram (IU/kg) infused intravenously over 10 minutes.
Area Under the Plasma FVIII Activity-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf)	15.21 IU*hour/mL Geometric Coefficient of Variation 58

PRIMARY outcome

Timeframe: Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose

Population: The PK parameter analysis population is defined as all participants enrolled and treated who have at least 1 of the PK parameters of primary interest reported.

Outcome measures

Measure	Xyntha 50 IU/kg n=13 Participants Participants were administered a single dose of recombinant antihemophilic factor (Xyntha) at 50 international units per kilogram (IU/kg) infused intravenously over 10 minutes.
Time to Reach Maximum Observed Plasma Concentration (Tmax)	0.500 hour Interval 0.25 to 3.0

PRIMARY outcome

Timeframe: Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose

Population: The PK parameter analysis population is defined as all participants enrolled and treated who have at least 1 of the PK parameters of primary interest reported.

Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

Outcome measures

Measure	Xyntha 50 IU/kg n=13 Participants Participants were administered a single dose of recombinant antihemophilic factor (Xyntha) at 50 international units per kilogram (IU/kg) infused intravenously over 10 minutes.
Clearance (CL)	3.295 mL/hour/kg Geometric Coefficient of Variation 56

PRIMARY outcome

Timeframe: Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose

Population: The PK parameter analysis population is defined as all participants enrolled and treated who have at least 1 of the PK parameters of primary interest reported.

Volume of distribution is the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vss is the volume of distribution at steady-state.

Outcome measures

Measure	Xyntha 50 IU/kg n=13 Participants Participants were administered a single dose of recombinant antihemophilic factor (Xyntha) at 50 international units per kilogram (IU/kg) infused intravenously over 10 minutes.
Volume of Distribution at Steady-State (Vss)	53.96 mL/kg Geometric Coefficient of Variation 29

PRIMARY outcome

Timeframe: Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose

Population: The PK parameter analysis population is defined as all participants enrolled and treated who have at least 1 of the PK parameters of primary interest reported.

Terminal phase rate constant is the absolute value of the slope of a linear regression during the terminal phase of the natural--logarithm transformed concentration--time profile.

Outcome measures

Measure	Xyntha 50 IU/kg n=13 Participants Participants were administered a single dose of recombinant antihemophilic factor (Xyntha) at 50 international units per kilogram (IU/kg) infused intravenously over 10 minutes.
Terminal Phase Rate Constant (Kel)	0.06039 1/hour Geometric Coefficient of Variation 39

PRIMARY outcome

Timeframe: Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose

Population: The PK parameter analysis population is defined as all participants enrolled and treated who have at least 1 of the PK parameters of primary interest reported.

Terminal half-life is the time measured for the plasma concentration to decrease by one half.

Outcome measures

Measure	Xyntha 50 IU/kg n=13 Participants Participants were administered a single dose of recombinant antihemophilic factor (Xyntha) at 50 international units per kilogram (IU/kg) infused intravenously over 10 minutes.
Terminal Elimination Half-Life (t1/2)	12.24 hour Standard Deviation 4.4172

PRIMARY outcome

Timeframe: Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose

Population: The PK parameter analysis population is defined as all participants enrolled and treated who have at least 1 of the PK parameters of primary interest reported.

MRT = AUMCinf / AUCinf, where AUMCinf is the area under the first moment curve from zero time to infinity calculated as AUMCinf = AUMCt + ((t x Ct) / kel) + (Ct / kel^2). AUMCt is the area under the first moment curve from zero time to time t calculated using the trapezoidal method.

Outcome measures

Measure	Xyntha 50 IU/kg n=13 Participants Participants were administered a single dose of recombinant antihemophilic factor (Xyntha) at 50 international units per kilogram (IU/kg) infused intravenously over 10 minutes.
Mean Residence Time (MRT)	16.37 hour Geometric Coefficient of Variation 38

PRIMARY outcome

Timeframe: Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose

Population: The PK parameter analysis population is defined as all participants enrolled and treated who have at least 1 of the PK parameters of primary interest reported.

Incremental recovery is the increase in circulating FVIII activity for every IU of Xyntha administered per kilogram of body weight.

Outcome measures

Measure	Xyntha 50 IU/kg n=13 Participants Participants were administered a single dose of recombinant antihemophilic factor (Xyntha) at 50 international units per kilogram (IU/kg) infused intravenously over 10 minutes.
Incremental Recovery (INCREC)	2.284 IU/deciliter (dL) per IU/kg Geometric Coefficient of Variation 44

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to Day 28

Population: The safety analysis population included all participants who received at least 1 dose of study drug.

An AE was any untoward medical occurrence in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-SAEs.

Outcome measures

Measure	Xyntha 50 IU/kg n=13 Participants Participants were administered a single dose of recombinant antihemophilic factor (Xyntha) at 50 international units per kilogram (IU/kg) infused intravenously over 10 minutes.
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) Number of participants with AEs	4 participants 44
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) Number of participants with SAEs	2 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to Day 4

Population: The safety analysis population included all participants who received at least 1 dose of study drug.

The following laboratory parameters were analyzed: hematology (hemoglobin, hematocrit, red blood cell count, RBC morphology, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); blood chemistry (blood urea nitrogen, creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid, albumin, and total protein; urinalysis (pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, urobilinogen, urine bilirubin, microscopy [if urine dipstick was positive for blood, protein, nitrites or leukocyte esterase]); others (urine drug screening, FVIII inhibitor assay, FVIII activity, prothrombin time [PT], activated partial thromboplastin time [APTT], anti-human immunodeficiency virus [HIV] 1, hepatitis C virus antibody [HCVAb], HAVAb, HBsAg, HBsAb, HBcAb). Only parameters which met abnormality criteria are reported.

Outcome measures

Measure	Xyntha 50 IU/kg n=13 Participants Participants were administered a single dose of recombinant antihemophilic factor (Xyntha) at 50 international units per kilogram (IU/kg) infused intravenously over 10 minutes.
Number of Participants With Laboratory Abnormalities Meeting the Criteria for Potential Clinical Concern APTT >1.1X upper limit of normal (ULN)	13 participants 44
Number of Participants With Laboratory Abnormalities Meeting the Criteria for Potential Clinical Concern Potassium <0.9X lower limit of normal (LLN)	1 participants
Number of Participants With Laboratory Abnormalities Meeting the Criteria for Potential Clinical Concern Urine leukocyte >=1	1 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to Day 4

Population: The safety analysis population included all participants who received at least 1 dose of study drug.

Vital signs assessment included pulse rate and blood pressure. Criteria for vital sign values meeting potential clinical concern included: supine pulse rate <50 beats per minute (bpm), >=30 bpm increase from baseline, or >25 bpm decrease from baseline; systolic blood pressure (SBP) <90 milliliters of mercury (mmHg), >=30 mmHg increase from baseline, or >=30 mmHg decrease from baseline; diastolic blood pressure (DBP) <50 mmHg, >=20 mmHg increase from baseline, or >=20 mmHg decrease from baseline.

Outcome measures

Measure	Xyntha 50 IU/kg n=13 Participants Participants were administered a single dose of recombinant antihemophilic factor (Xyntha) at 50 international units per kilogram (IU/kg) infused intravenously over 10 minutes.
Number of Participants With Potentially Clinically Significant Vital Signs Findings Supine SBP <90 mmHg	0 participants 44
Number of Participants With Potentially Clinically Significant Vital Signs Findings Supine DBP <50 mmHg	0 participants
Number of Participants With Potentially Clinically Significant Vital Signs Findings Supine Pulse Rate <50 bpm	0 participants
Number of Participants With Potentially Clinically Significant Vital Signs Findings Supine SBP >=30 mmHg Increase From Baseline	0 participants
Number of Participants With Potentially Clinically Significant Vital Signs Findings Supine DBP >=20 mmHg Increase From Baseline	0 participants
Number of Participants With Potentially Clinically Significant Vital Signs Findings Supine Pulse Rate >=30 bpm Increase From Baseline	1 participants
Number of Participants With Potentially Clinically Significant Vital Signs Findings Supine SBP >=30 mmHg Decrease From Baseline	0 participants
Number of Participants With Potentially Clinically Significant Vital Signs Findings Supine DBP >=20 mmHg Decrease From Baseline	0 participants
Number of Participants With Potentially Clinically Significant Vital Signs Findings Supine Pulse Rate >=25 bpm Increase From Baseline	0 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 4

Population: The safety analysis population included all participants who received at least 1 dose of study drug.

As with all FVIII products, participants using Xyntha were monitored for the development of FVIII inhibitors. Values >= 0.6 Bethesda Unit (BU) per mL were considered positive results.

Outcome measures

Measure	Xyntha 50 IU/kg n=13 Participants Participants were administered a single dose of recombinant antihemophilic factor (Xyntha) at 50 international units per kilogram (IU/kg) infused intravenously over 10 minutes.
Number of Participants With Positive FVIII Inhibitor Activity at Day 4	2 participants 44

Adverse Events

Xyntha 50 IU/kg

Serious events: 2 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Measure	Xyntha 50 IU/kg n=13 participants at risk Participants were administered a single dose of recombinant antihemophilic factor (Xyntha) at 50 international units per kilogram (IU/kg) infused intravenously over 10 minutes.
Blood and lymphatic system disorders Factor VIII inhibition	15.4% 2/13 • Number of events 2 • Baseline up to Day 28

Other adverse events

Measure	Xyntha 50 IU/kg n=13 participants at risk Participants were administered a single dose of recombinant antihemophilic factor (Xyntha) at 50 international units per kilogram (IU/kg) infused intravenously over 10 minutes.
Gastrointestinal disorders Abdominal pain	7.7% 1/13 • Number of events 1 • Baseline up to Day 28
Nervous system disorders Headache	7.7% 1/13 • Number of events 1 • Baseline up to Day 28

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: ClinicalTrials.gov_Inquiries@pfizer.com

Results disclosure agreements

• Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
• Publication restrictions are in place

Restriction type: OTHER