Hemophilia B
Conditions
Keywords
PF 06838435, Hemophilia, Hemophilia B, Factor IX, FIX, Gene Therapy, Infusion, rAAV Spark100 hFIX Padua, rAAV Spark100-hFIX-R338L, R338L, BeneGene 2, Hematological Diseases, Annualized bleeding rate (ABR)
Brief summary
This study will evaluate the efficacy and safety of PF-06838435 (a gene therapy drug) in adult male participants with moderately severe to severe hemophilia B (participants that have a Factor IX circulating activity of 2% or less). The gene therapy is designed to introduce genetic material into cells to compensate for missing or non-functioning Factor IX. Eligible study participants will have completed a minimum 6 months of routine Factor IX prophylaxis therapy during the lead in study (C0371004). Participants will be dosed once (intravenously) and will be evaluated over the course of 6 years. The main objective of the study will evaluate the annualized bleeding rate \[ABR\] for participants treated with gene therapy versus standard of care (SOC) therapy (FIX prophylaxis replacement regimen).
Interventions
BIOLOGICALPF-06838435/ fidanacogene elaparvovec
Gene Therapy
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Males who completed 6 months of Factor IX prophylaxis therapy during the lead-in study (C0371004) prior to providing consent at the screening visit for this study. * Documented moderately severe to severe hemophilia B (Factor IX activity \< =2%) * Previous experience with FIX therapy (=\>50 documented exposure days to a FIX protein product) * Suspension of prophylaxis therapy for hemophilia B after administration of the study drug * Laboratory values (hemoglobin, platelets and creatinine) within study specified limits * Agree to contraception until components of the drug are eliminated from their body * Capable of giving signed informed consent
Exclusion criteria
* Anti-AAVRh74var neutralizing antibodies (nAb) titer above the established threshold (ie, positive for nAb). * History of inhibitor to Factor IX or inhibitor detected during screening. Clinical signs or symptoms of decreased response to Factor IX * Hypersensitivity to Factor IX replacement product or IV immunoglobulin administration * History of chronic infection or other chronic disease * Any conditions associated with increased thromboembolic risk * Concurrent clinically significant major disease or condition unsuitable for participation and/or may interfere with the interpretation of study results * Laboratory values at screening visit that are abnormal or outside acceptable study limits * Current unstable liver or biliary disease * Currently on antiviral therapy for hepatitis B or C * Planned surgical procedure requiring Factor IX surgical prophylactic factor treatment 15 months from screening visit * Use of restricted therapies (e.g., blood products, acetylsalicylic acid \[aspirin\] or ibuprofen, other investigational therapy, and by-passing agents) * Previously dosed in a gene therapy research trial at any time or in an interventional clinical study within 12 weeks of screening visit * Active hepatitis B or C; hepatitis B surface antigen, hepatitis B virus deoxyribonucleic acid positivity, or hepatitis C virus ribonucleic acid positivity * Significant liver disease * Serological evidence of HIV1 or HIV2 infection with either CD4+ cell count \<=200 mm3 and/or a viral load \>20 copies/mL * Study and sponsor staff involved in the conduct of the study and their families * Unable to comply with study procedures * Sensitivity to heparin or heparin induced thrombocytopenia * Sensitivity to any of the study interventions, or components thereof, or drug or other allergy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annualized Bleeding Rate (ABR) for Total Bleeds (Treated and Untreated) 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) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ABR for Treated Bleeds 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) | 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. |
| Annualized Infusion Rate (AIR) of Exogenous FIX 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) | 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. |
| Steady State Circulating Factor IX (FIX:C) From Week 12 to Month 15 | 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. |
| Circulating Factor IX (FIX:C) at Week 12, Week 24, Week 65 | 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. |
| Annualized Factor IX (FIX) Consumption 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) | 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. |
| ABR for Spontaneous Bleeds 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) | 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. |
| ABR for Traumatic Bleeds 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) | 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. |
| ABR for Untreated Bleeds 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) | 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. |
| Number of Target Joint Bleeds 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) | 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. |
| Percentage of the Participants Without Bleeds From Week 12 to Month 15 | 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. |
| Change From Baseline in Joint Health as Measured by the Hemophilia Joint Health Score (HJHS) Instrument at Month 12 | Baseline, 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. |
| Change From Baseline in Hemophilia Quality of Life (Haem A QoL) Physical Health Domain at Month 12 | Baseline, 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. |
| Change From Baseline in Hemophilia Activities List (HAL) Complex Lower Extremity Activities Component Score at Month 12 | Baseline, 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. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Maximum up to 6 years (Week 312) after PF-06838435 infusion | Results would be posted at secondary completion date. |
| Number of Participants With Adverse Events of Special Interest | Maximum up to 6 years (Week 312) after PF-06838435 infusion | Results would be posted at secondary completion date. |
| Number of Participants With Positive Neutralizing Antibody (nAb) to Adeno-associated Virus Vector (AAV) and Anti-Drug Antibody (ADA) | Maximum up to 6 years (Week 312) after PF-06838435 infusion | Results would be posted at secondary completion date. |
| ABR for Total Bleeds (Treated and Untreated) Through the Study | Maximum up to 6 years (Week 312) after PF-06838435 infusion | Results would be posted at secondary completion date. |
| ABR for Treated Bleeds Through the Study | Maximum up to 6 years (Week 312) after PF-06838435 infusion | Results would be posted at secondary completion date. |
| AIR of Exogenous Factor IX Through the Study | Maximum up to 6 years (Week 312) after PF-06838435 infusion | Results would be posted at secondary completion date. |
| FIX: C Level Through the Study | Maximum up to 6 years (Week 312) after PF-06838435 infusion | Results would be posted at secondary completion date. |
| Annualized Factor IX Consumption Through the Study | Maximum up to 6 years (Week 312) after PF-06838435 infusion | Results would be posted at secondary completion date. |
| ABR for Spontaneous and Traumatic, and Untreated Bleeds Through the Study | Maximum up to 6 years (Week 312) after PF-06838435 infusion | Results would be posted at secondary completion date. |
| Change From Baseline in Joint Health as Measured by the HJHS Instrument Through the Study | Baseline, 6 years | Results would be posted at secondary completion date. |
| Number of Target Joint Bleeds Through the Study | Maximum up to 6 years (Week 312) after PF-06838435 infusion | Results would be posted at secondary completion date. |
| Change From Baseline in Haem A QoL Physical Health Domain Through the Study | Baseline, Maximum up to 6 years (Week 312) after PF-06838435 infusion | Results would be posted at secondary completion date. |
| Change From Baseline in HAL Complex Lower Extremity Activities Component Score Through the Study | Baseline, 6 years | Results would be posted at secondary completion date. |
Countries
Australia, Brazil, Canada, France, Germany, Greece, Italy, Japan, Saudi Arabia, South Korea, Spain, Sweden, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Participant flow
Recruitment details
Participants with moderately severe to severe hemophilia B, who completed a minimum 6 months of routine Factor IX prophylaxis therapy during the lead-in study C0371004 (NCT03587116), were enrolled in this study.
Pre-assignment details
A total of 51 participants were screened in this study and 45 participants received a single dose of PF-06838435 (fidanacogene elaparvovec). Results presented are for primary outcome measures and only those secondary measures whose analysis was complete on a data cutoff date of 16 November 2022 (primary completion date \[PCD\]).
Participants by arm
| Arm | Count |
|---|---|
| PF-06838435 All participants enrolled in the study and who received PF-06838435 infusion. | 45 |
| Total | 45 |
Baseline characteristics
| Characteristic | PF-06838435 |
|---|---|
| Age, Continuous | 33.18 Years STANDARD_DEVIATION 10.947 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 35 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 8 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 7 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 33 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 45 |
| other Total, other adverse events | 37 / 45 |
| serious Total, serious adverse events | 7 / 45 |
Outcome results
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.
Time frame: 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)
Population: Dosed analysis set included all participants enrolled in the study who received PF-06838435 infusion.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FIX Prophylaxis | Annualized Bleeding Rate (ABR) for Total Bleeds (Treated and Untreated) From Week 12 to Month 15 | 4.43 Total bleeds per year |
| PF-06838435 | Annualized Bleeding Rate (ABR) for Total Bleeds (Treated and Untreated) From Week 12 to Month 15 | 1.30 Total bleeds per year |
p-value: 0.008195% CI: [-5.44, -0.81]Generalized linear model (GLM)
Secondary
ABR for Spontaneous and Traumatic, and Untreated Bleeds Through the Study
Results would be posted at secondary completion date.
Time frame: Maximum up to 6 years (Week 312) after PF-06838435 infusion
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.
Time frame: 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)
Population: Dosed analysis set included all participants enrolled in the study who received PF-06838435 infusion.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FIX Prophylaxis | ABR for Spontaneous Bleeds From Week 12 to Month 15 | 3.24 Spontaneous bleeds per year |
| PF-06838435 | ABR for Spontaneous Bleeds From Week 12 to Month 15 | 0.69 Spontaneous bleeds per year |
p-value: 0.019195% CI: [-4.67, -0.42]Generalized linear model (GLM)
Secondary
ABR for Total Bleeds (Treated and Untreated) Through the Study
Results would be posted at secondary completion date.
Time frame: Maximum up to 6 years (Week 312) after PF-06838435 infusion
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.
Time frame: 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)
Population: Dosed analysis set included all participants enrolled in the study who received PF-06838435 infusion.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FIX Prophylaxis | ABR for Traumatic Bleeds From Week 12 to Month 15 | 1.16 Traumatic bleeds per year |
| PF-06838435 | ABR for Traumatic Bleeds From Week 12 to Month 15 | 0.59 Traumatic bleeds per year |
p-value: 0.152895% CI: [-1.35, 0.21]Generalized linear model (GLM)
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.
Time frame: 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)
Population: Dosed analysis set included all participants enrolled in the study who received PF-06838435 infusion.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FIX Prophylaxis | ABR for Treated Bleeds From Week 12 to Month 15 | 3.35 Treated bleeds per year |
| PF-06838435 | ABR for Treated Bleeds From Week 12 to Month 15 | 0.73 Treated bleeds per year |
p-value: 0.001995% CI: [-4.27, -0.96]Generalized linear model (GLM)
Secondary
ABR for Treated Bleeds Through the Study
Results would be posted at secondary completion date.
Time frame: Maximum up to 6 years (Week 312) after PF-06838435 infusion
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.
Time frame: 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)
Population: Dosed analysis set included all participants enrolled in the study who received PF-06838435 infusion.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FIX Prophylaxis | ABR for Untreated Bleeds From Week 12 to Month 15 | 1.07 Untreated bleeds per year |
| PF-06838435 | ABR for Untreated Bleeds From Week 12 to Month 15 | 0.57 Untreated bleeds per year |
p-value: 0.373895% CI: [-1.63, 0.61]Generalized linear model (GLM)
Secondary
AIR of Exogenous Factor IX Through the Study
Results would be posted at secondary completion date.
Time frame: 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.
Time frame: Maximum up to 6 years (Week 312) after PF-06838435 infusion
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.
Time frame: 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)
Population: Dosed analysis set included all participants enrolled in the study who received PF-06838435 infusion.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FIX Prophylaxis | Annualized Factor IX (FIX) Consumption From Week 12 to Month 15 | 3170.74 IU/kg per year | Standard Deviation 1634.753 |
| PF-06838435 | Annualized Factor IX (FIX) Consumption From Week 12 to Month 15 | 235.04 IU/kg per year | Standard Deviation 538.977 |
p-value: <0.000195% CI: [-3403.1, -2468.3]Paired t-test
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.
Time frame: 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)
Population: Dosed analysis set included all participants enrolled in the study who received PF-06838435 infusion.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FIX Prophylaxis | Annualized Infusion Rate (AIR) of Exogenous FIX From Week 12 to Month 15 | 58.83 Exogenous infusions per year | Standard Deviation 29.056 |
| PF-06838435 | Annualized Infusion Rate (AIR) of Exogenous FIX From Week 12 to Month 15 | 4.46 Exogenous infusions per year | Standard Deviation 10.028 |
Comparison: The treatment difference (PF-06838435 - FIX Prophylaxis) estimate (95% CI) and p-value were obtained from paired t-test.p-value: <0.000195% CI: [-63.64, -45.1]Paired t-test
Secondary
Change From Baseline in Haem A QoL Physical Health Domain Through the Study
Results would be posted at secondary completion date.
Time frame: 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.
Time frame: Baseline, 6 years
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.
Time frame: Baseline, Month 12
Population: Dosed analysis set included all participants enrolled in the study who received PF-06838435 infusion. Here, Number of Participants Analyzed signifies number of participants evaluable for this outcome measure and Number Analyzed signifies number of participants evaluable for specified rows of respective arms.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| FIX Prophylaxis | Change From Baseline in Hemophilia Activities List (HAL) Complex Lower Extremity Activities Component Score at Month 12 | Baseline | 67.06 Units on a scale |
| FIX Prophylaxis | Change From Baseline in Hemophilia Activities List (HAL) Complex Lower Extremity Activities Component Score at Month 12 | Change at Month 12 | 7.59 Units on a scale |
p-value: 0.0237Paired t-test
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.
Time frame: Baseline, Month 12
Population: Dosed analysis set included all participants enrolled in the study who received PF-06838435 infusion. Here, Number of Participants Analyzed signifies number of participants evaluable for this outcome measure and Number Analyzed signifies number of participants evaluable for specified rows of respective arms.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| FIX Prophylaxis | Change From Baseline in Hemophilia Quality of Life (Haem A QoL) Physical Health Domain at Month 12 | Baseline | 31.00 Units on a scale |
| FIX Prophylaxis | Change From Baseline in Hemophilia Quality of Life (Haem A QoL) Physical Health Domain at Month 12 | Change at Month 12 | -7.70 Units on a scale |
p-value: 0.0052Paired t-test
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.
Time frame: Baseline, Month 12
Population: Dosed analysis set included all participants enrolled in the study who received PF-06838435 infusion. Here, Number of Participants Analyzed signifies number of participants evaluable for this outcome measure and Number Analyzed signifies number of participants evaluable for specified rows of respective arms.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| FIX Prophylaxis | Change From Baseline in Joint Health as Measured by the Hemophilia Joint Health Score (HJHS) Instrument at Month 12 | Baseline | 17.8 Units on a scale |
| FIX Prophylaxis | Change From Baseline in Joint Health as Measured by the Hemophilia Joint Health Score (HJHS) Instrument at Month 12 | Change at Month 12 | -2.6 Units on a scale |
p-value: 0.0117Paired t-test
Secondary
Change From Baseline in Joint Health as Measured by the HJHS Instrument Through the Study
Results would be posted at secondary completion date.
Time frame: Baseline, 6 years
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.
Time frame: Week 12, Week 24, Week 65
Population: Dosed analysis set: participants enrolled in the study who received PF-06838435 infusion. The assessments at the visits following participant withdrawal/dropout/FIX prophylaxis resumption were imputed as 1.9%. Number Analyzed: at each row represents the number of participants with valid FIX:C assessments at the respective time points. All participants reported under 'Number of Participants Analyzed' contributed data to the table; however, may not have evaluable data for every row.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FIX Prophylaxis | Circulating Factor IX (FIX:C) at Week 12, Week 24, Week 65 | Week 12: One-stage Assay (Actin-FSL Reagent) | 13.52 Percentage of Normal | Standard Deviation 8.134 |
| FIX Prophylaxis | Circulating Factor IX (FIX:C) at Week 12, Week 24, Week 65 | Week 12: One-stage Assay (SynthASil Reagent) | 27.79 Percentage of Normal | Standard Deviation 15.226 |
| FIX Prophylaxis | Circulating Factor IX (FIX:C) at Week 12, Week 24, Week 65 | Week 12: Chromogenic Assay | 13.91 Percentage of Normal | Standard Deviation 9.302 |
| FIX Prophylaxis | Circulating Factor IX (FIX:C) at Week 12, Week 24, Week 65 | Week 24: One-stage Assay (Actin-FSL Reagent) | 13.10 Percentage of Normal | Standard Deviation 11.144 |
| FIX Prophylaxis | Circulating Factor IX (FIX:C) at Week 12, Week 24, Week 65 | Week 24: One-stage Assay (SynthASil Reagent) | 27.67 Percentage of Normal | Standard Deviation 21.34 |
| FIX Prophylaxis | Circulating Factor IX (FIX:C) at Week 12, Week 24, Week 65 | Week 24: Chromogenic Assay | 14.83 Percentage of Normal | Standard Deviation 12.961 |
| FIX Prophylaxis | Circulating Factor IX (FIX:C) at Week 12, Week 24, Week 65 | Week 65: One-stage Assay (Actin-FSL Reagent) | 13.10 Percentage of Normal | Standard Deviation 12.792 |
| FIX Prophylaxis | Circulating Factor IX (FIX:C) at Week 12, Week 24, Week 65 | Week 65: One-stage Assay (SynthASil Reagent) | 27.47 Percentage of Normal | Standard Deviation 25.739 |
| FIX Prophylaxis | Circulating Factor IX (FIX:C) at Week 12, Week 24, Week 65 | Week 65: Chromogenic Assay | 15.82 Percentage of Normal | Standard Deviation 16.996 |
Secondary
FIX: C Level Through the Study
Results would be posted at secondary completion date.
Time frame: 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.
Time frame: 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.
Time frame: Maximum up to 6 years (Week 312) after PF-06838435 infusion
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
Results would be posted at secondary completion date.
Time frame: Maximum up to 6 years (Week 312) after PF-06838435 infusion
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.
Time frame: 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)
Population: Dosed analysis set included all participants enrolled in the study who received PF-06838435 infusion.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FIX Prophylaxis | Number of Target Joint Bleeds From Week 12 to Month 15 | 2.9 Target joint bleeds | Standard Deviation 7.81 |
| PF-06838435 | Number of Target Joint Bleeds From Week 12 to Month 15 | 0.3 Target joint bleeds | Standard Deviation 1.02 |
Secondary
Number of Target Joint Bleeds Through the Study
Results would be posted at secondary completion date.
Time frame: Maximum up to 6 years (Week 312) after PF-06838435 infusion
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.
Time frame: Week 12 to Month 15
Population: Dosed analysis set included all participants enrolled in the study who received PF-06838435 infusion.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FIX Prophylaxis | Percentage of the Participants Without Bleeds From Week 12 to Month 15 | Without treated and untreated bleeds | 64.4 Percentage of participants |
| FIX Prophylaxis | Percentage of the Participants Without Bleeds From Week 12 to Month 15 | Without treated bleeds | 73.3 Percentage of participants |
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.
Time frame: Week 12 to Month 15
Population: Dosed analysis set included all participants enrolled in the study who received PF-06838435 infusion. The assessments at the visits following participant withdrawal/dropout/FIX prophylaxis resumption were imputed as 1.9%. Here, Number Analyzed signifies number of participants evaluable for specified rows of respective arms.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| FIX Prophylaxis | Steady State Circulating Factor IX (FIX:C) From Week 12 to Month 15 | Week 12 to Month 15: One-stage Assay (Actin-FSL Reagent) | 12.62 Percentage of Normal | Standard Deviation 8.92 |
| FIX Prophylaxis | Steady State Circulating Factor IX (FIX:C) From Week 12 to Month 15 | Week 12 to Month 15: One-stage Assay (SynthASil Reagent) | 25.90 Percentage of Normal | Standard Deviation 16.89 |
| FIX Prophylaxis | Steady State Circulating Factor IX (FIX:C) From Week 12 to Month 15 | Week 12 to Month 15: Chromogenic Assay | 13.49 Percentage of Normal | Standard Deviation 10.4 |
Comparison: Week 12 to Month 15p-value: <0.0001One-sided t-statistic testing