Hemophilia A
Conditions
Brief summary
The goal of this study is to give gather more information on how safe and well Jivi works in patients with severe hemophilia A. Jivi has been approved by various regulatory agencies, including the FDA, Health Canada, Japanese Health Authority and the European Medicinal Agency. 25 patients will be enrolled and will stay for 1 to 2 years in this study depending on their treatment frequency. Researcher will monitor during the course of the study whether patients are developing antibodies (a protein made by the body in response to the drug) affecting the effectiveness of Jivi. In addition information on bleedings and patient's wellbeing will be collected.
Interventions
The recommended starting dose is every 5 days treatment (45 IU/kg)- An assessment of response to treatment will be performed at the next scheduled visit after 10-15 ED (8-10 weeks). Participants may be assigned to different dosing regimens (every 7 days or 2x/week) or continue with every 5 days regimen, according to individual bleeding tendency and needs at investigator's discretion.
Sponsors
Bayer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants must ≥ 18 years of age inclusive, at the time of signing the informed consent. * Participants with severe hemophilia A (FVIII: C\<1%) * PTPs (Previously treated patients) (≥150 ED (Exposure day)) on prophylaxis treatment before enrollment * Participants who are immunocompetent. If human immunodeficiency virus (HIV) positive, cluster of differentiation 4 (CD4)+ lymphocyte count \>200/mm\*3 * Participants who are willing to complete an eDiary * Male participants * Capable of giving signed informed consent
Exclusion criteria
* Any other inherited or acquired bleeding disorder in addition to Hemophilia A. * Platelet count \< 100,000/mm\*3 * Creatinine \> 2x upper limit of normal * AST or ALT \> 5x upper limit of normal (AST: aspartate aminotransferase; ALT: alanine aminotransferase) * The participant has a planned major surgery. * The participant is currently participating in another investigational drug study, or has participated in a clinical study involving an investigational drug within 30 days of signing informed consent or previous treatment in a clinical phase III study with BAY 94-9027 (now marketed as Jivi). * Current evidence (by central laboratory) or history of inhibitor to FVIII with a titer ≥ 0.6 Bethesda unit (BU). * Known hypersensitivity to the drug substance, excipients, or mouse or hamster protein.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| FVIII Inhibitor Development by the Nijmegen Bethesda Assay | Observed for 100 exposure days (EDs), up to 2 years | FVIII inhibitor testing was performed using the Nijmegen-modified Bethesda assay. A positive inhibitor result was defined as a threshold of ≥0.6 BU/mL at the central laboratory and had to be confirmed with a second blood sample. After confirmation of the positive result, the inhibitor was to be reported as a serious adverse event (SAE). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Observed for 100 exposure days (EDs), up to 2 years | Treatment-emergent AEs were defined as those that started after the first dose of study drug and up to 7 days after the last dose. |
| Development of Treatment-emergent Anti-PEG Antibodies | Observed for 100 exposure days (EDs), up to 2 years | Anti-PEG antibody: antibody against the PEG moiety determined by enzyme-linked immunosorbent assay (ELISA). For participants with a positive result, IgM antibodies were tested. |
| Annualized Bleeding Rate (ABR) | Observed for 100 exposure days (EDs), up to 2 years | ABR is number of all bleeds per individual treatment period annualized to a 1-year time interval. |
Countries
Bulgaria, Denmark, Greece, Italy, Norway, Poland, Spain
Participant flow
Recruitment details
The study was conducted at 13 centers in 7 countries between 23 SEP 2019 (First participant first visit) and 26 Aug 2022 (last participant's data from the last visit were received). Bulgaria (2 centers), Denmark (1 centers), Spain (3 centers), Greece (1 center), Italy (3 centers), Norway (1 center), Poland (2 centers).
Pre-assignment details
36 participants were screened into the study (signed informed consent form (ICF)). 4 participants were screening failed.
Participants by arm
| Arm | Count |
|---|---|
| Severe Hemophilia A Patients With Damoctocog Alfa Pegol (Jivi, BAY94-9027) Treatment Prophylaxis regimens with every 5 days treatment (45-60 IU/kg), or every 7 days (60 IU/kg) or twice per week (40 IU/kg). | 32 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Other | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Severe Hemophilia A Patients With Damoctocog Alfa Pegol (Jivi, BAY94-9027) Treatment |
|---|---|
| Age, Continuous | 42.8 years STANDARD_DEVIATION 15.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 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 | 0 Participants |
| Race (NIH/OMB) White | 32 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 32 |
| other Total, other adverse events | 15 / 32 |
| serious Total, serious adverse events | 2 / 32 |
Outcome results
Primary
FVIII Inhibitor Development by the Nijmegen Bethesda Assay
FVIII inhibitor testing was performed using the Nijmegen-modified Bethesda assay. A positive inhibitor result was defined as a threshold of ≥0.6 BU/mL at the central laboratory and had to be confirmed with a second blood sample. After confirmation of the positive result, the inhibitor was to be reported as a serious adverse event (SAE).
Time frame: Observed for 100 exposure days (EDs), up to 2 years
Population: Safety analysis set (SAF): A participant was included in the SAF if he received at least 1 infusion of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Severe Hemophilia A Patients With Damoctocog Alfa Pegol (Jivi, BAY94-9027) Treatment | FVIII Inhibitor Development by the Nijmegen Bethesda Assay | Any positive FVIII inhibitor | 0 Participants |
| Severe Hemophilia A Patients With Damoctocog Alfa Pegol (Jivi, BAY94-9027) Treatment | FVIII Inhibitor Development by the Nijmegen Bethesda Assay | High titer FVIII inhibitor | 0 Participants |
| Severe Hemophilia A Patients With Damoctocog Alfa Pegol (Jivi, BAY94-9027) Treatment | FVIII Inhibitor Development by the Nijmegen Bethesda Assay | Low titer FVIII inhibitor | 0 Participants |
Secondary
Annualized Bleeding Rate (ABR)
ABR is number of all bleeds per individual treatment period annualized to a 1-year time interval.
Time frame: Observed for 100 exposure days (EDs), up to 2 years
Population: Modified intent-to-treat set (mITT): A participant was included in the mITT if he received at least 1 infusion of study drug and had injection/bleeding data available for at least 3 months. This time period is considered the minimum observation time for a reliable annualization of the observed bleed rate.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Severe Hemophilia A Patients With Damoctocog Alfa Pegol (Jivi, BAY94-9027) Treatment | Annualized Bleeding Rate (ABR) | 1.8 Bleeds per year |
Secondary
Development of Treatment-emergent Anti-PEG Antibodies
Anti-PEG antibody: antibody against the PEG moiety determined by enzyme-linked immunosorbent assay (ELISA). For participants with a positive result, IgM antibodies were tested.
Time frame: Observed for 100 exposure days (EDs), up to 2 years
Population: Safety analysis set (SAF): A participant was included in the SAF if he received at least 1 infusion of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Severe Hemophilia A Patients With Damoctocog Alfa Pegol (Jivi, BAY94-9027) Treatment | Development of Treatment-emergent Anti-PEG Antibodies | 3 participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Treatment-emergent AEs were defined as those that started after the first dose of study drug and up to 7 days after the last dose.
Time frame: Observed for 100 exposure days (EDs), up to 2 years
Population: Safety analysis set (SAF): A participant was included in the SAF if he received at least 1 infusion of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Severe Hemophilia A Patients With Damoctocog Alfa Pegol (Jivi, BAY94-9027) Treatment | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any AE | 21 participants |
| Severe Hemophilia A Patients With Damoctocog Alfa Pegol (Jivi, BAY94-9027) Treatment | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any study drug-related AE | 3 participants |
| Severe Hemophilia A Patients With Damoctocog Alfa Pegol (Jivi, BAY94-9027) Treatment | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any AE related to procedures required by the protocol | 0 participants |
| Severe Hemophilia A Patients With Damoctocog Alfa Pegol (Jivi, BAY94-9027) Treatment | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any AE leading to discontinuation of study drug | 2 participants |
| Severe Hemophilia A Patients With Damoctocog Alfa Pegol (Jivi, BAY94-9027) Treatment | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any SAE | 2 participants |
| Severe Hemophilia A Patients With Damoctocog Alfa Pegol (Jivi, BAY94-9027) Treatment | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any study drug-related SAE | 0 participants |
| Severe Hemophilia A Patients With Damoctocog Alfa Pegol (Jivi, BAY94-9027) Treatment | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any SAE related to procedures required by the protocol | 0 participants |
| Severe Hemophilia A Patients With Damoctocog Alfa Pegol (Jivi, BAY94-9027) Treatment | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any SAE leading to discontinuation of study drug | 0 participants |
| Severe Hemophilia A Patients With Damoctocog Alfa Pegol (Jivi, BAY94-9027) Treatment | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | AE with outcome death | 0 participants |