Trial Outcomes & Findings for Dose-finding Study of SPK-8016 Gene Therapy in Patients With Hemophilia A to Support Evaluation in Individuals With FVIII Inhibitors (NCT NCT03734588)
NCT ID: NCT03734588
Last Updated: 2024-02-23
Results Overview
An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
COMPLETED
PHASE1/PHASE2
4 participants
Up to week 52
2024-02-23
Participant Flow
A dose-finding part of this trial was planned but no participants were enrolled into the higher dose arms. All participants received SPK-8016 5x10\^11 vg/kg
Participant milestones
| Measure |
SPK-8016
Participants received a single intravenous infusion of SPK-8016 at 5x10\^11 vector genomes per kilogram body weight (vg/kg).
|
|---|---|
|
Overall Study
STARTED
|
4
|
|
Overall Study
COMPLETED
|
4
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Dose-finding Study of SPK-8016 Gene Therapy in Patients With Hemophilia A to Support Evaluation in Individuals With FVIII Inhibitors
Baseline characteristics by cohort
| Measure |
SPK-8016
n=4 Participants
Participants received a single intravenous infusion of SPK-8016 at 5x10\^11 vg/kg.
|
|---|---|
|
Age, Continuous
|
36.3 years
STANDARD_DEVIATION 19.29 • n=99 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
4 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Up to week 52Population: The FAS included all enrolled participants who received the infusion of SPK-8016.
An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Outcome measures
| Measure |
SPK-8016
n=4 Participants
Participants received a single intravenous infusion of SPK-8016 at 5x10\^11 vg/kg.
|
|---|---|
|
Number of Participants With Adverse Events (AEs)
|
4 Participants
|
PRIMARY outcome
Timeframe: Up to week 52Population: The FAS included all enrolled participants who received the infusion of SPK-8016.
Outcome measures
| Measure |
SPK-8016
n=4 Participants
Participants received a single intravenous infusion of SPK-8016 at 5x10\^11 vg/kg.
|
|---|---|
|
Number of Participants With Hepatic Transaminase Elevation Requiring Immunosuppression.
|
0 Participants
|
PRIMARY outcome
Timeframe: Up to week 52Population: The FAS included all enrolled participants who received the infusion of SPK-8016.
Outcome measures
| Measure |
SPK-8016
n=4 Participants
Participants received a single intravenous infusion of SPK-8016 at 5x10\^11 vg/kg.
|
|---|---|
|
Peak FVIII Activity Levels Assessed by Coagulation Clotting Assays
|
NA percentage of normal activity
Data was not analyzed due to low number of participants enrolled. Data values are not reported due to privacy concerns related to low enrollment.
|
PRIMARY outcome
Timeframe: Up to week 52Population: The FAS included all enrolled participants who received the infusion of SPK-8016.
Outcome measures
| Measure |
SPK-8016
n=4 Participants
Participants received a single intravenous infusion of SPK-8016 at 5x10\^11 vg/kg.
|
|---|---|
|
Steady-state FVIII Activity Levels Assessed by Coagulation Clotting Assays
|
NA percentage of normal activity
Standard Deviation NA
Insufficient number of participants with events
|
PRIMARY outcome
Timeframe: From 28 days post vector administration up to week 52Population: The FAS included all enrolled participants who received the infusion of SPK-8016.
Outcome measures
| Measure |
SPK-8016
n=4 Participants
Participants received a single intravenous infusion of SPK-8016 at 5x10\^11 vg/kg.
|
|---|---|
|
Number of Bleeding Events (Spontaneous and Traumatic) Since 28 Day Post Vector Administration
Traumatic
|
6 Number of bleeding events
|
|
Number of Bleeding Events (Spontaneous and Traumatic) Since 28 Day Post Vector Administration
Spontaneous
|
1 Number of bleeding events
|
PRIMARY outcome
Timeframe: From 28 days post vector administration up to week 52Population: The FAS included all enrolled participants who received the infusion of SPK-8016.
Outcome measures
| Measure |
SPK-8016
n=4 Participants
Participants received a single intravenous infusion of SPK-8016 at 5x10\^11 vg/kg.
|
|---|---|
|
Annualized Infusion Rate
|
NA Annualized Infusion Rate
Data was not analyzed due to low number of participants enrolled. Data values are not reported due to privacy concerns related to low enrollment.
|
SECONDARY outcome
Timeframe: Up to week 52Population: The FAS included all enrolled participants who received the infusion of SPK-8016.
Outcome measures
| Measure |
SPK-8016
n=4 Participants
Participants received a single intravenous infusion of SPK-8016 at 5x10\^11 vg/kg.
|
|---|---|
|
Time to Achieve Steady-state FVIII Activity Levels
|
NA hours
Standard Deviation NA
Insufficient number of participants with events
|
SECONDARY outcome
Timeframe: Up to week 52Population: Results were uninterpretable due to a technical error.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to week 52Population: The FAS includes all enrolled participants who received the infusion of SPK-8016.
Outcome measures
| Measure |
SPK-8016
n=4 Participants
Participants received a single intravenous infusion of SPK-8016 at 5x10\^11 vg/kg.
|
|---|---|
|
Number of Participants With Immune Responses to AAV Capsid Protein and BDD-hFVIII Transgene
|
3 Participants
|
Adverse Events
SPK-8016
Serious adverse events
| Measure |
SPK-8016
n=4 participants at risk
Participants received a single intravenous infusion of SPK-8016 at 5x10\^11 vg/kg
|
|---|---|
|
Gastrointestinal disorders
Food Poisoning
|
25.0%
1/4 • Up to week 52
|
|
Gastrointestinal disorders
Haematemesis
|
25.0%
1/4 • Up to week 52
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
25.0%
1/4 • Up to week 52
|
Other adverse events
| Measure |
SPK-8016
n=4 participants at risk
Participants received a single intravenous infusion of SPK-8016 at 5x10\^11 vg/kg
|
|---|---|
|
Endocrine disorders
Cushingoid
|
25.0%
1/4 • Up to week 52
|
|
Eye disorders
Vision Blurred
|
25.0%
1/4 • Up to week 52
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
25.0%
1/4 • Up to week 52
|
|
Gastrointestinal disorders
Diarrhoea
|
25.0%
1/4 • Up to week 52
|
|
Gastrointestinal disorders
Dyspepsia
|
25.0%
1/4 • Up to week 52
|
|
Gastrointestinal disorders
Food Poisoning
|
25.0%
1/4 • Up to week 52
|
|
Gastrointestinal disorders
Nausea
|
25.0%
1/4 • Up to week 52
|
|
Gastrointestinal disorders
Tooth Loss
|
25.0%
1/4 • Up to week 52
|
|
Gastrointestinal disorders
Vomiting
|
25.0%
1/4 • Up to week 52
|
|
General disorders
Fatigue
|
25.0%
1/4 • Up to week 52
|
|
General disorders
Feeling Hot
|
25.0%
1/4 • Up to week 52
|
|
General disorders
Oedema Peripheral
|
25.0%
1/4 • Up to week 52
|
|
General disorders
Swelling Face
|
25.0%
1/4 • Up to week 52
|
|
Hepatobiliary disorders
Drug-Induced Liver Injury
|
25.0%
1/4 • Up to week 52
|
|
Infections and infestations
Candida Infection
|
25.0%
1/4 • Up to week 52
|
|
Infections and infestations
Gastroenteritis Viral
|
25.0%
1/4 • Up to week 52
|
|
Infections and infestations
Nasopharyngitis
|
25.0%
1/4 • Up to week 52
|
|
Infections and infestations
Oral Herpes
|
25.0%
1/4 • Up to week 52
|
|
Infections and infestations
Pharyngitis Streptococcal
|
25.0%
1/4 • Up to week 52
|
|
Infections and infestations
Skin Infection
|
25.0%
1/4 • Up to week 52
|
|
Infections and infestations
Tooth Abscess
|
25.0%
1/4 • Up to week 52
|
|
Injury, poisoning and procedural complications
Contusion
|
25.0%
1/4 • Up to week 52
|
|
Injury, poisoning and procedural complications
Limb Crushing Injury
|
25.0%
1/4 • Up to week 52
|
|
Injury, poisoning and procedural complications
Scratch
|
25.0%
1/4 • Up to week 52
|
|
Injury, poisoning and procedural complications
Skin Abrasion
|
25.0%
1/4 • Up to week 52
|
|
Injury, poisoning and procedural complications
Skin Laceration
|
25.0%
1/4 • Up to week 52
|
|
Injury, poisoning and procedural complications
Thermal Burn
|
25.0%
1/4 • Up to week 52
|
|
Injury, poisoning and procedural complications
Tooth Fracture
|
25.0%
1/4 • Up to week 52
|
|
Investigations
Blood Glucose Increased
|
25.0%
1/4 • Up to week 52
|
|
Investigations
Weight Increased
|
50.0%
2/4 • Up to week 52
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
25.0%
1/4 • Up to week 52
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
50.0%
2/4 • Up to week 52
|
|
Musculoskeletal and connective tissue disorders
Joint Noise
|
25.0%
1/4 • Up to week 52
|
|
Musculoskeletal and connective tissue disorders
Joint Swelling
|
25.0%
1/4 • Up to week 52
|
|
Musculoskeletal and connective tissue disorders
Muscular Weakness
|
25.0%
1/4 • Up to week 52
|
|
Nervous system disorders
Dizziness
|
25.0%
1/4 • Up to week 52
|
|
Nervous system disorders
Headache
|
50.0%
2/4 • Up to week 52
|
|
Nervous system disorders
Hypoaesthesia
|
25.0%
1/4 • Up to week 52
|
|
Nervous system disorders
Lethargy
|
50.0%
2/4 • Up to week 52
|
|
Psychiatric disorders
Anxiety
|
25.0%
1/4 • Up to week 52
|
|
Psychiatric disorders
Libido Decreased
|
25.0%
1/4 • Up to week 52
|
|
Renal and urinary disorders
Pollakiuria
|
25.0%
1/4 • Up to week 52
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
25.0%
1/4 • Up to week 52
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain
|
50.0%
2/4 • Up to week 52
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngeal Erythema
|
25.0%
1/4 • Up to week 52
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
25.0%
1/4 • Up to week 52
|
|
Skin and subcutaneous tissue disorders
Acne
|
25.0%
1/4 • Up to week 52
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
25.0%
1/4 • Up to week 52
|
|
Skin and subcutaneous tissue disorders
Rash
|
25.0%
1/4 • Up to week 52
|
|
Skin and subcutaneous tissue disorders
Skin Irritation
|
25.0%
1/4 • Up to week 52
|
Additional Information
Tiffany Chang, MD, MAS Clinical Development Lead, Hematology
Spark Therapeutics
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place