Trial Outcomes & Findings for A Gene Therapy Study for Hemophilia B (NCT NCT02484092)
NCT ID: NCT02484092
Last Updated: 2020-06-16
Results Overview
Physical examination included examination of the head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. The examination assessed the participants for any potential changes in general appearance, the respiratory and cardiovascular systems, as well as towards participant reported symptoms. Findings were considered to be clinically significant based on investigator's decision.
COMPLETED
PHASE2
15 participants
Baseline up to Week 52
2020-06-16
Participant Flow
A total of 22 participants were screened, 15 participants were assigned to treatment and completed study. All 15 participants received the lowest dose in the study (5 x 10\^11 vg/kg). No participants were assigned to the 2 higher dose arms. Results presented here are from the lowest dose level.
Participant milestones
| Measure |
SPK-9001 (5 x 10^11 vg/kg) IV Infusion
Participants were infused with 100 IU/kg of their usual FIX protein product over 10 minutes at Day 0 visit. Following the bolus infusion of the usual FIX protein product, the participant was infused with SPK-9001 (5 x 10\^11 vg/kg) for approximately 60 minutes via infusion pump.
|
|---|---|
|
Overall Study
STARTED
|
15
|
|
Overall Study
COMPLETED
|
15
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Gene Therapy Study for Hemophilia B
Baseline characteristics by cohort
| Measure |
SPK-9001 (5 x 10^11 vg/kg) IV Infusion
n=15 Participants
Participants were infused with 100 IU/kg of their usual FIX protein product over 10 minutes at Day 0 visit. Following the bolus infusion of the usual FIX protein product, the participant was infused with SPK-9001 (5 x 10\^11 vg/kg) for approximately 60 minutes via infusion pump.
|
|---|---|
|
Age, Continuous
|
38.6 Years
STANDARD_DEVIATION 14.5 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White or Caucasian
|
12 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Multiple
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline up to Week 52Population: All participants who received the infusion of SPK-9001.
Physical examination included examination of the head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. The examination assessed the participants for any potential changes in general appearance, the respiratory and cardiovascular systems, as well as towards participant reported symptoms. Findings were considered to be clinically significant based on investigator's decision.
Outcome measures
| Measure |
SPK-9001 (5 x 10^11 vg/kg)
n=15 Participants
Participants were infused with 100 IU/kg of their usual FIX protein product over 10 minutes at Day 0 visit. Following the bolus infusion of the usual FIX protein product, the participant was infused with SPK-9001 (5 x 10\^11 vg/kg) for approximately 60 minutes via infusion pump.
|
|---|---|
|
Number of Participants With Clinically Significant Change From Baseline in Physical Examination Findings
|
0 Participants
|
PRIMARY outcome
Timeframe: Baseline up to Week 52Population: All participants who received the infusion of SPK-9001.
Vital signs (temperature, respiratory rate, pulse rate, height, weight, systolic and diastolic blood pressure) were obtained with participant in the seated position, after having sat calmly for at least 5 minutes. Clinical significance of vital signs was determined at the investigator's discretion.
Outcome measures
| Measure |
SPK-9001 (5 x 10^11 vg/kg)
n=15 Participants
Participants were infused with 100 IU/kg of their usual FIX protein product over 10 minutes at Day 0 visit. Following the bolus infusion of the usual FIX protein product, the participant was infused with SPK-9001 (5 x 10\^11 vg/kg) for approximately 60 minutes via infusion pump.
|
|---|---|
|
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
|
0 Participants
|
PRIMARY outcome
Timeframe: Baseline up to Week 52Population: All participants who received the infusion of SPK-9001.
Following parameters were analyzed for laboratory examination: hematology (neutrophils, lymphocytes, monocytes, eosinophils, basophils, red blood cell \[RBC\] count, hemoglobin, hematocrit, platelet count); liver function (albumin, total bilirubin, total protein, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alkaline phosphatase, GGT); Lipid panel (HDL, VLDL, triglycerides, total cholesterol); clinical chemistry (sodium, potassium, chloride, bicarbonate, glucose, phosphate, serum creatinine, BUN); urinalysis (specific gravity, pH, glucose, protein, blood, ketones; coagulation, immunology, etc. Investigators determined which laboratory abnormalities were reported as treatment-emergent adverse events (TEAEs).
Outcome measures
| Measure |
SPK-9001 (5 x 10^11 vg/kg)
n=15 Participants
Participants were infused with 100 IU/kg of their usual FIX protein product over 10 minutes at Day 0 visit. Following the bolus infusion of the usual FIX protein product, the participant was infused with SPK-9001 (5 x 10\^11 vg/kg) for approximately 60 minutes via infusion pump.
|
|---|---|
|
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAE
|
2 Participants
|
PRIMARY outcome
Timeframe: Baseline up to Week 52Population: All participants who received the infusion of SPK-9001.
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. A serious adverse event (SAE) was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. AEs included both SAEs and AEs. An AE was regarded as TEAE if the start date was on or after the infusion of SPK-9001 but before participant's last visit on study (or the date of withdrawal/the date of being lost to follow-up). Severe TEAEs were TEAEs that interfered significantly with participants' usual function. Treatment-related TEAEs were determined by the investigator.
Outcome measures
| Measure |
SPK-9001 (5 x 10^11 vg/kg)
n=15 Participants
Participants were infused with 100 IU/kg of their usual FIX protein product over 10 minutes at Day 0 visit. Following the bolus infusion of the usual FIX protein product, the participant was infused with SPK-9001 (5 x 10\^11 vg/kg) for approximately 60 minutes via infusion pump.
|
|---|---|
|
Number of Participants With Drug -Related TEAEs and Serious Adverse Events (SAEs)
Drug-related TEAE
|
2 Participants
|
|
Number of Participants With Drug -Related TEAEs and Serious Adverse Events (SAEs)
Drug-related Serious TEAE
|
0 Participants
|
PRIMARY outcome
Timeframe: Baseline up to Week 52Population: All participants who received the infusion of SPK-9001.
Peripheral blood mononuclear cells (PBMC) results by interferon gamma enzyme-linked immunospot assay (ELISPOT) to assess cellular immune responses to AAV capsid and to FIX were presented. The ELISPOT is a type of assay that focuses on quantitatively measuring the frequency of cytokine secretion for a single cell. The positive ELISPOT results suggested a T-cell reaction to capsid protein.
Outcome measures
| Measure |
SPK-9001 (5 x 10^11 vg/kg)
n=15 Participants
Participants were infused with 100 IU/kg of their usual FIX protein product over 10 minutes at Day 0 visit. Following the bolus infusion of the usual FIX protein product, the participant was infused with SPK-9001 (5 x 10\^11 vg/kg) for approximately 60 minutes via infusion pump.
|
|---|---|
|
Number of Participants With Positive Immune Reponses Against Adeno-associated Virus Vector (AAV) Capsid
|
2 Participants
|
PRIMARY outcome
Timeframe: Baseline up to Week 52Population: All participants who received the infusion of SPK-9001.
Based on non-clinical studies in non-human primates (NHPs), it was not predicted that vector-derived FIX:C activity levels \>150% of normal would be achieved in this study. However, thrombin antithrombin (TAT) levels as thrombotic potential were to be measured if vector derived FIX:C activity levels \>150% of normal were achieved in any participant during the study. Blood samples for TAT at Day 0 visit (prior to FIX protein product infusion) were used to establish baseline value.
Outcome measures
| Measure |
SPK-9001 (5 x 10^11 vg/kg)
n=15 Participants
Participants were infused with 100 IU/kg of their usual FIX protein product over 10 minutes at Day 0 visit. Following the bolus infusion of the usual FIX protein product, the participant was infused with SPK-9001 (5 x 10\^11 vg/kg) for approximately 60 minutes via infusion pump.
|
|---|---|
|
Number of Participants Who Reached > 150% Vector-derived FIX:C Activity Level After SPK-9001 Infusion
|
0 Participants
|
PRIMARY outcome
Timeframe: Baseline up to Week 52Population: All participants who received the infusion of SPK-9001.
FIX inhibitors were measured using the Bethesda assay from the central and local laboratory. The Bethesda assay measures the amount of factor (FIX) inactivated when the plasma from the patient is incubated with an external source of factor for 2 hours at 37ºC. Inhibitor levels are quantified in Bethesda units (BU). An inhibitor titer of ≥ 0.6 BU/ml is to be taken as clinically significant.
Outcome measures
| Measure |
SPK-9001 (5 x 10^11 vg/kg)
n=15 Participants
Participants were infused with 100 IU/kg of their usual FIX protein product over 10 minutes at Day 0 visit. Following the bolus infusion of the usual FIX protein product, the participant was infused with SPK-9001 (5 x 10\^11 vg/kg) for approximately 60 minutes via infusion pump.
|
|---|---|
|
Number of Participants With FIX Inhibitor
|
0 Participants
|
PRIMARY outcome
Timeframe: Day 0 and Week 52Population: Participants who had received 100 IU/kg of FIX protein product infusion and completed the blood sample collection within the first 3 hours post infusion for FIX protein product enabling determination of FIX incremental recovery.
Incremental recovery was determined as the peak factor level recorded within the first 3 hours after infusion and was reported as (IU/ml)/(IU/kg), using the formula:(\[Activity IU/mL peak post infusion\] - \[Activity IU/mL pre-infusion\]) / (IU/kg infused).
Outcome measures
| Measure |
SPK-9001 (5 x 10^11 vg/kg)
n=15 Participants
Participants were infused with 100 IU/kg of their usual FIX protein product over 10 minutes at Day 0 visit. Following the bolus infusion of the usual FIX protein product, the participant was infused with SPK-9001 (5 x 10\^11 vg/kg) for approximately 60 minutes via infusion pump.
|
|---|---|
|
Incremental Recovery of FIX Product
Day 0
|
0.0100 [IU/ml]/[IU/kg]
Standard Deviation 0.00242
|
|
Incremental Recovery of FIX Product
Week 52
|
0.0162 [IU/ml]/[IU/kg]
Standard Deviation 0.01351
|
SECONDARY outcome
Timeframe: Baseline up to Week 52Population: Participants who had received SPK-9001 and had collected vector-derived FIX:C activity levels enabling acceptable determination of the peak and steady-state derived activity level.
All samples collected from participants for plasma FIX activity levels were analyzed and used to determine peak and steady-state vector-derived circulating FIX activity levels. The vector-derived endogenous (not affected by intercurrent FIX product infusions) FIX:C activity levels were characterized by post-treatment population mean. Dose escalation and dose level expansion strategies were employed in the study based on vector-derived FIX activity levels as well as any immune responses against AAV capsid. Steady-state levels were based on 2 separate vector-derived FIX:C activity level measurements (at least 2 weeks apart) starting from Week 8-12 with adequate washout.
Outcome measures
| Measure |
SPK-9001 (5 x 10^11 vg/kg)
n=15 Participants
Participants were infused with 100 IU/kg of their usual FIX protein product over 10 minutes at Day 0 visit. Following the bolus infusion of the usual FIX protein product, the participant was infused with SPK-9001 (5 x 10\^11 vg/kg) for approximately 60 minutes via infusion pump.
|
|---|---|
|
FIX:C Activity
Steady-State Level
|
22.9 Percentage of Normal
Standard Deviation 9.89
|
|
FIX:C Activity
Peak Activity
|
29.1 Percentage of Normal
Standard Deviation 11.63
|
SECONDARY outcome
Timeframe: Week 12 up to Week 52Population: Participants who had received SPK-9001 and had collected vector-derived FIX:C activity levels enabling acceptable determination of the peak and steady-state derived activity level.
The vector-derived endogenous (not affected by intercurrent FIX product infusions) FIX:C activity antigen levels were characterized by post-treatment population mean.
Outcome measures
| Measure |
SPK-9001 (5 x 10^11 vg/kg)
n=15 Participants
Participants were infused with 100 IU/kg of their usual FIX protein product over 10 minutes at Day 0 visit. Following the bolus infusion of the usual FIX protein product, the participant was infused with SPK-9001 (5 x 10\^11 vg/kg) for approximately 60 minutes via infusion pump.
|
|---|---|
|
Change From Baseline in FIX:C Antigen Level at Steady State
Week 18
|
-5.8 Percentage of Normal
Standard Deviation 21.81
|
|
Change From Baseline in FIX:C Antigen Level at Steady State
Week 12
|
-4.4 Percentage of Normal
Standard Deviation 19.26
|
|
Change From Baseline in FIX:C Antigen Level at Steady State
Week 14
|
-4.7 Percentage of Normal
Standard Deviation 23.11
|
|
Change From Baseline in FIX:C Antigen Level at Steady State
Week 16
|
-4.7 Percentage of Normal
Standard Deviation 19.79
|
|
Change From Baseline in FIX:C Antigen Level at Steady State
Week 22
|
-4.6 Percentage of Normal
Standard Deviation 22.06
|
|
Change From Baseline in FIX:C Antigen Level at Steady State
Week 26
|
-6.6 Percentage of Normal
Standard Deviation 20.64
|
|
Change From Baseline in FIX:C Antigen Level at Steady State
Week 32
|
-7.1 Percentage of Normal
Standard Deviation 20.48
|
|
Change From Baseline in FIX:C Antigen Level at Steady State
Week 42
|
-4.9 Percentage of Normal
Standard Deviation 19.87
|
|
Change From Baseline in FIX:C Antigen Level at Steady State
Week 52
|
-6.9 Percentage of Normal
Standard Deviation 19.70
|
Adverse Events
SPK-9001 (5 x 10^11 vg/kg) IV Infusion
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
SPK-9001 (5 x 10^11 vg/kg) IV Infusion
n=15 participants at risk
Participants were infused with 100 IU/kg of their usual FIX protein product over 10 minutes at Day 0 visit. Following the bolus infusion of the usual FIX protein product, the participant was infused with SPK-9001 (5 x 10\^11 vg/kg) for approximately 60 minutes via infusion pump.
|
|---|---|
|
Blood and lymphatic system disorders
Microcytic anaemia
|
6.7%
1/15 • Baseline up to Week 52
|
|
Blood and lymphatic system disorders
Normocytic anaemia
|
6.7%
1/15 • Baseline up to Week 52
|
|
Cardiac disorders
Palpitations
|
6.7%
1/15 • Baseline up to Week 52
|
|
Eye disorders
Conjunctivitis allergic
|
6.7%
1/15 • Baseline up to Week 52
|
|
Gastrointestinal disorders
Abdominal discomfort
|
6.7%
1/15 • Baseline up to Week 52
|
|
Gastrointestinal disorders
Abdominal distension
|
6.7%
1/15 • Baseline up to Week 52
|
|
Gastrointestinal disorders
Abdominal pain lower
|
6.7%
1/15 • Baseline up to Week 52
|
|
Gastrointestinal disorders
Aphthous ulcer
|
6.7%
1/15 • Baseline up to Week 52
|
|
Gastrointestinal disorders
Diarrhoea
|
6.7%
1/15 • Baseline up to Week 52
|
|
Gastrointestinal disorders
Dyspepsia
|
13.3%
2/15 • Baseline up to Week 52
|
|
Gastrointestinal disorders
Food poisoning
|
6.7%
1/15 • Baseline up to Week 52
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
13.3%
2/15 • Baseline up to Week 52
|
|
Gastrointestinal disorders
Nausea
|
6.7%
1/15 • Baseline up to Week 52
|
|
General disorders
Catheter site bruise
|
6.7%
1/15 • Baseline up to Week 52
|
|
General disorders
Face oedema
|
6.7%
1/15 • Baseline up to Week 52
|
|
Immune system disorders
Seasonal allergy
|
6.7%
1/15 • Baseline up to Week 52
|
|
Infections and infestations
Gastroenteritis
|
6.7%
1/15 • Baseline up to Week 52
|
|
Infections and infestations
Nasopharyngitis
|
20.0%
3/15 • Baseline up to Week 52
|
|
Infections and infestations
Otitis media
|
6.7%
1/15 • Baseline up to Week 52
|
|
Infections and infestations
Pharyngitis
|
6.7%
1/15 • Baseline up to Week 52
|
|
Infections and infestations
Upper respiratory tract infection
|
33.3%
5/15 • Baseline up to Week 52
|
|
Injury, poisoning and procedural complications
Ligament sprain
|
6.7%
1/15 • Baseline up to Week 52
|
|
Injury, poisoning and procedural complications
Muscle injury
|
6.7%
1/15 • Baseline up to Week 52
|
|
Injury, poisoning and procedural complications
Muscle strain
|
20.0%
3/15 • Baseline up to Week 52
|
|
Investigations
Transaminases increased
|
13.3%
2/15 • Baseline up to Week 52
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
6.7%
1/15 • Baseline up to Week 52
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
20.0%
3/15 • Baseline up to Week 52
|
|
Musculoskeletal and connective tissue disorders
Calcification of muscle
|
6.7%
1/15 • Baseline up to Week 52
|
|
Musculoskeletal and connective tissue disorders
Costochondritis
|
6.7%
1/15 • Baseline up to Week 52
|
|
Musculoskeletal and connective tissue disorders
Exostosis
|
6.7%
1/15 • Baseline up to Week 52
|
|
Musculoskeletal and connective tissue disorders
Joint range of motion decreased
|
6.7%
1/15 • Baseline up to Week 52
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
6.7%
1/15 • Baseline up to Week 52
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
6.7%
1/15 • Baseline up to Week 52
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
6.7%
1/15 • Baseline up to Week 52
|
|
Musculoskeletal and connective tissue disorders
Tendonitis
|
13.3%
2/15 • Baseline up to Week 52
|
|
Nervous system disorders
Dizziness
|
6.7%
1/15 • Baseline up to Week 52
|
|
Nervous system disorders
Dysgeusia
|
6.7%
1/15 • Baseline up to Week 52
|
|
Nervous system disorders
Headache
|
13.3%
2/15 • Baseline up to Week 52
|
|
Nervous system disorders
Hypoaesthesia
|
6.7%
1/15 • Baseline up to Week 52
|
|
Nervous system disorders
Sinus headache
|
6.7%
1/15 • Baseline up to Week 52
|
|
Psychiatric disorders
Insomnia
|
6.7%
1/15 • Baseline up to Week 52
|
|
Psychiatric disorders
Irritability
|
6.7%
1/15 • Baseline up to Week 52
|
|
Renal and urinary disorders
Haematuria
|
6.7%
1/15 • Baseline up to Week 52
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
13.3%
2/15 • Baseline up to Week 52
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
6.7%
1/15 • Baseline up to Week 52
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
13.3%
2/15 • Baseline up to Week 52
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
6.7%
1/15 • Baseline up to Week 52
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
6.7%
1/15 • Baseline up to Week 52
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
6.7%
1/15 • Baseline up to Week 52
|
|
Respiratory, thoracic and mediastinal disorders
Upper-airway cough syndrome
|
6.7%
1/15 • Baseline up to Week 52
|
|
Skin and subcutaneous tissue disorders
Rash macular
|
6.7%
1/15 • Baseline up to Week 52
|
Additional Information
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