Outcome
| Type |
Measure |
Description |
Time frame |
Safety issue |
| Primary |
Annualized Bleeding Rate (ABR) for Total Bleeds (Treated and Untreated) From Week 12 to Month 15 |
ABR = number of total bleeding episodes on study during the given time period) *365.25/ (Date of last day - date of first day +1) in that time period. Surgical procedures were excluded from summary/analyses. Treated Bleed: An event necessitating administration of coagulation factor within 72 hours of signs or symptoms of bleeding (protocol definition, unless specifically referring to untreated bleed). Untreated Bleed: A bleeding event not necessitating administration of coagulation factor within 72 hours of signs or symptoms of bleeding. This outcome measure compared data collected from lead-in study C0371004 and from current study C0371002. Pre-infusion period = at least 6 months of prospectively collected data while receiving FIX prophylaxis replacement therapy in lead-in study C0371004 up to dosing in current study C0371002. |
Pre-infusion period: minimum of 6 months through first dose of current study, an average of 1.31 years (FIX Prophylaxis arm); Week 12 to Month 15 post infusion in current study (PF-06838435 arm) |
|
| Secondary |
ABR for Treated Bleeds From Week 12 to Month 15 |
ABR = number of total bleeding episodes on study during the given time period) *365.25/ (Date of last day - date of first day +1) in that time period. Surgical procedures were excluded from summary/analyses. Treated Bleed: An event necessitating administration of coagulation factor within 72 hours of signs or symptoms of bleeding (protocol definition, unless specifically referring to untreated bleed). This outcome measure compared data collected from lead-in study C0371004 and from current study C0371002. Pre-infusion period = at least 6 months of prospectively collected data while receiving FIX prophylaxis replacement therapy in lead-in study C0371004 up to dosing in current study C0371002. |
Pre-infusion period: minimum of 6 months through first dose of current study, an average of 1.31 years (FIX Prophylaxis arm); Week 12 to Month 15 post infusion in current study (PF-06838435 arm) |
|
| Secondary |
Annualized Infusion Rate (AIR) of Exogenous FIX From Week 12 to Month 15 |
AIR = number of exogenous infusions (for any reason) received during given time period *365.25/ (Date of last day - date of first day +1) in that time period. This outcome measure compared data collected from lead-in study C0371004 and from current study C0371002. Pre-infusion period = at least 6 months of prospectively collected data while receiving FIX prophylaxis replacement therapy in lead-in study C0371004 up to dosing in current study C0371002. |
Pre-infusion period: minimum of 6 months through first dose of current study, an average of 1.31 years (FIX Prophylaxis arm); Week 12 to Month 15 post infusion in current study (PF-06838435 arm) |
|
| Secondary |
Steady State Circulating Factor IX (FIX:C) From Week 12 to Month 15 |
The certified central clinical laboratory analyzed the sample by two one-stage assays and a chromogenic assay. The first one-stage assay was performed on BCSXP analyzer with Actin-FSL reagent. The second one-stage assay used the same analyzer but SynthAsil as reagent. Data reported in this Outcome Measure is the geometric mean of all assessments from week 12 to Month 15. |
Week 12 to Month 15 |
|
| Secondary |
Circulating Factor IX (FIX:C) at Week 12, Week 24, Week 65 |
The certified central clinical laboratory analyzed the sample by two one-stage assays and a chromogenic assay. The first one-stage assay was performed on BCSXP analyzer with Actin-FSL reagent. The second one-stage assay used the same analyzer but SynthAsil as reagent. |
Week 12, Week 24, Week 65 |
|
| Secondary |
Annualized Factor IX (FIX) Consumption From Week 12 to Month 15 |
Annualized FIX consumption was reported by International Units per kilogram (IU/kg). This outcome measure compared data collected from lead-in study C0371004 and from current study C0371002. Pre-infusion period = at least 6 months of prospectively collected data while receiving FIX prophylaxis replacement therapy in lead-in study C0371004 up to dosing in current study C0371002. Data reported in this Outcome Measure is average of all assessments from Week 12 to Month 15. |
Pre-infusion period: minimum of 6 months through first dose of current study, an average of 1.31 years (FIX Prophylaxis arm); Week 12 to Month 15 post infusion in current study (PF-06838435 arm) |
|
| Secondary |
ABR for Spontaneous Bleeds From Week 12 to Month 15 |
ABR = number of total bleeding episodes on study during the given time period) *365.25/ (Date of last day - date of first day +1) in that time period. Surgical procedures were excluded from summary/analyses. Surgical procedures were excluded from summary/analyses. Spontaneous Bleeds: Bleeding for no apparent/known reason particularly into the joints, muscles, and soft tissues. This outcome measure compared data collected from lead-in study C0371004 and from current study C0371002. Pre-infusion period = at least 6 months of prospectively collected data while receiving FIX prophylaxis replacement therapy in lead-in study C0371004 up to dosing in current study C0371002. |
Pre-infusion period: minimum of 6 months through first dose of current study, an average of 1.31 years (FIX Prophylaxis arm); Week 12 to Month 15 post infusion in current study (PF-06838435 arm) |
|
| Secondary |
ABR for Traumatic Bleeds From Week 12 to Month 15 |
ABR = number of total bleeding episodes on study during the given time period) *365.25/ (Date of last day - date of first day +1) in that time period. Surgical procedures were excluded from summary/analyses. Surgical procedures were excluded from summary/analyses. Traumatic Bleeds: Bleeding event occurring for an apparent/known reason. This outcome measure compared data collected from lead-in study C0371004 and from current study C0371002. Pre-infusion period = at least 6 months of prospectively collected data while receiving FIX prophylaxis replacement therapy in lead-in study C0371004 up to dosing in current study C0371002. |
Pre-infusion period: minimum of 6 months through first dose of current study, an average of 1.31 years (FIX Prophylaxis arm); Week 12 to Month 15 post infusion in current study (PF-06838435 arm) |
|
| Secondary |
ABR for Untreated Bleeds From Week 12 to Month 15 |
ABR = number of total bleeding episodes on study during the given time period) *365.25/ (Date of last day - date of first day +1) in that time period. Surgical procedures were excluded from summary/analyses. Surgical procedures were excluded from summary/analyses. Untreated Bleed: A bleeding event not necessitating administration of coagulation factor within 72 hours of signs or symptoms of bleeding. This outcome measure compared data collected from lead-in study C0371004 and from current study C0371002. Pre-infusion period = at least 6 months of prospectively collected data while receiving FIX prophylaxis replacement therapy in lead-in study C0371004 up to dosing in current study C0371002. |
Pre-infusion period: minimum of 6 months through first dose of current study, an average of 1.31 years (FIX Prophylaxis arm); Week 12 to Month 15 post infusion in current study (PF-06838435 arm) |
|
| Secondary |
Number of Target Joint Bleeds From Week 12 to Month 15 |
Target Joint: Defined as a major joint (e.g., hip, elbow, wrist, shoulder, knee, and ankle) into which repeated bleeds occurred (three or more spontaneous bleeds into a single joint within a consecutive 6-month period). A target joint was considered resolved when there were =<2 bleeds into the joint within a 12-month period. Joint Bleed: A bleeding episode characterized by rapid loss of range of motion as compared with baseline that was associated with any combination of the following: pain or an unusual sensation in the joint, palpable swelling, and warmth of the skin over the joint. This outcome measure compared data collected from lead-in study C0371004 and from current study C0371002. Pre-infusion period = at least 6 months of prospectively collected data while receiving FIX prophylaxis replacement therapy in lead-in study C0371004 up to dosing in current study C0371002. |
Pre-infusion period: minimum of 6 months through first dose of current study, an average of 1.31 years (FIX Prophylaxis arm); Week 12 to Month 15 post infusion in current study (PF-06838435 arm) |
|
| Secondary |
Percentage of the Participants Without Bleeds From Week 12 to Month 15 |
Percentage of participants without bleeds (total bleeds and treated bleeds) were summarized by type from Week 12 to Month 15. |
Week 12 to Month 15 |
|
| Secondary |
Change From Baseline in Joint Health as Measured by the Hemophilia Joint Health Score (HJHS) Instrument at Month 12 |
A qualified healthcare professional assessed six joints (left ankle, right ankle, left elbow, right elbow, left knee, right knee) scored from 0 to 20 based on: duration of swelling, muscle atrophy, crepitus, flexion loss, extension loss, instability, joint pain, and strength. Gait was scored (0 to 4) based on walking, stairs, running, hopping on one leg. Total score = sum of scores from all joints + gait score ranged from 0 to 124, with the higher the number equating to more severe joint damage. |
Baseline, Month 12 |
|
| Secondary |
Change From Baseline in Hemophilia Quality of Life (Haem A QoL) Physical Health Domain at Month 12 |
The Haem-A-QoL questionnaire contained 46 items with ten domains that assessed health in the following areas: Physical Health; Feelings; View of Self; Sports and Leisure; Work and School; Dealing with Haemophilia; Treatment; Future; Family Planning; and Partnership and Sexuality. The physical health domain was considered as the primary domain in this questionnaire, had a transformed score range from 0 to 100, with lower scores representing higher quality of life. In this Outcome Measure Physical Health domain scores of Haem A QoL are reported. |
Baseline, Month 12 |
|
| Secondary |
Change From Baseline in Hemophilia Activities List (HAL) Complex Lower Extremity Activities Component Score at Month 12 |
The HAL was a multiple domain measure of the impact of hemophilia on functional abilities in adults. The 7 domains of this instrument contained 42 items in total, as follows: lying/sitting/kneeling/standing; lower (leg) functioning; upper (arm) functioning; transportation; self-care; household tasks; and sports/leisure. Selected items from five of the domains were used to create three components: upper extremity; basic lower extremity; and complex lower extremity activities. The component score of "complex lower extremity activities" was the most important in this questionnaire, had a transformed score range from 0 to 100, higher values indicated less functional limitations in performing tasks. |
Baseline, Month 12 |
|
| Secondary |
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs |
Results would be posted at secondary completion date. |
Maximum up to 6 years (Week 312) after PF-06838435 infusion |
|
| Secondary |
Number of Participants With Adverse Events of Special Interest |
Results would be posted at secondary completion date. |
Maximum up to 6 years (Week 312) after PF-06838435 infusion |
|
| Secondary |
Number of Participants With Positive Neutralizing Antibody (nAb) to Adeno-associated Virus Vector (AAV) and Anti-Drug Antibody (ADA) |
Results would be posted at secondary completion date. |
Maximum up to 6 years (Week 312) after PF-06838435 infusion |
|
| Secondary |
ABR for Total Bleeds (Treated and Untreated) Through the Study |
Results would be posted at secondary completion date. |
Maximum up to 6 years (Week 312) after PF-06838435 infusion |
|
| Secondary |
ABR for Treated Bleeds Through the Study |
Results would be posted at secondary completion date. |
Maximum up to 6 years (Week 312) after PF-06838435 infusion |
|
| Secondary |
AIR of Exogenous Factor IX Through the Study |
Results would be posted at secondary completion date. |
Maximum up to 6 years (Week 312) after PF-06838435 infusion |
|
| Secondary |
FIX: C Level Through the Study |
Results would be posted at secondary completion date. |
Maximum up to 6 years (Week 312) after PF-06838435 infusion |
|
| Secondary |
Annualized Factor IX Consumption Through the Study |
Results would be posted at secondary completion date. |
Maximum up to 6 years (Week 312) after PF-06838435 infusion |
|
| Secondary |
ABR for Spontaneous and Traumatic, and Untreated Bleeds Through the Study |
Results would be posted at secondary completion date. |
Maximum up to 6 years (Week 312) after PF-06838435 infusion |
|
| Secondary |
Change From Baseline in Joint Health as Measured by the HJHS Instrument Through the Study |
Results would be posted at secondary completion date. |
Baseline, 6 years |
|
| Secondary |
Number of Target Joint Bleeds Through the Study |
Results would be posted at secondary completion date. |
Maximum up to 6 years (Week 312) after PF-06838435 infusion |
|
| Secondary |
Change From Baseline in Haem A QoL Physical Health Domain Through the Study |
Results would be posted at secondary completion date. |
Baseline, Maximum up to 6 years (Week 312) after PF-06838435 infusion |
|
| Secondary |
Change From Baseline in HAL Complex Lower Extremity Activities Component Score Through the Study |
Results would be posted at secondary completion date. |
Baseline, 6 years |
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