Haemophilia A
Conditions
Brief summary
This trial is conducted in Asia, Europe and the United States of America (USA). The aim of the trial is to evaluate safety of immune tolerance induction (ITI) treatment with turoctocog alfa (a recombinant factor VIII) in patients who have developed neutralising antibodies against factor VIII after exposure to subcutaneous turoctocog alfa pegol during participation in NN7170-4213 (NCT02994407)
Interventions
DRUGTuroctocog alfa
Intravenous (i.v., under the skin) administration.A maximum dose of 200 IU/kg daily. The maximum treatment period for this trial is 24 months and the patient(s) will be called for visit to the clinic every 3rd month.
Sponsors
Novo Nordisk A/S
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Previous participation in the NN7170-4213 trial (male, age at least 18 years (part A) and age at least 12 years (part B)) * Development of a confirmed high titre neutralising antibody towards factor VIII (greater than 5 Bethesda Unit) after exposure to subcutaneous turoctocog alfa pegol in the NN7170-4213 trial or development of a confirmed clinically relevant low titre inhibitor (at least 0.6 to below or equal to 5 Bethesda Unit), defined as factor VIII activity measures (recovery) and/or bleedpattern indicating a lack of clinical response to factor VIII treatment
Exclusion criteria
* Known or suspected hypersensitivity to trial product(s) or related products, defined as allergic reactions * Participation in another clinical trial within 1 month before screening (except participation in NN7170-4213) * Any disorder, except for conditions associated with Haemophilia A which in the investigator's opinion might jeopardise patients' safety or compliance with the protocol * Currently receiving immune tolerance induction treatment with a factor VIII containing product other than turoctocog alfa
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Adverse Events | Month 0 - up to month 12 | An adverse event (AE) was any untoward medical occurrence in a participant administered a medicinal product, and which does not necessarily have a causal relationship with this treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response to FVIII ITI Treatment (Success, Partial Success, Failure, Other) | Month 12 | ITI treatment response was categorized as: 1. Success: Undetectable inhibitor titre \<0.6 bethesda units (BU) (or lower limit of quantification \[LLoQ\] if above 0.6 BU); Normalised FVIII in vivo recovery, defined as ≥0.013 international units (IU) per milliliter per IU per kilogram ((IU/ml)/(IU/kg)) (66% of expected incremental recovery); turoctocog alfa half-life ≥7 hours (based on FVIII activity) after 72 hours treatment-free washout period. 2. Partial success: Inhibitor titre ≤5 BU; Clinical effect of turoctocog alfa therapy as judged by the investigator. 3. Failure (one criterion had to be fulfilled): Failure to attain defined success or partial success after 24 months of ITI treatment with turoctocog alfa; Decrease in inhibitor titre after 12 months of ITI treatment \<20% compared to peak titre. 4. Other: Participants not fulfilling the above criteria e.g. early withdrawal from ITI treatment, lack of adherence to recommended ITI protocol etc. |
Countries
Austria, Bulgaria, France, Germany, Serbia, Turkey (Türkiye), United Kingdom
Participant flow
Recruitment details
The trial was conducted at 1 trial site in Germany.
Pre-assignment details
Previously treated participants with severe haemophilia A (FVIII activity \<1% according to medical records) who had developed clinically relevant FVIII inhibitors in trial NN7170-4213 were offered immune tolerance induction (ITI) treatment with turoctocog alfa.
Participants by arm
| Arm | Count |
|---|---|
| Turoctocog Alfa The participant received intravenous (i.v.) injection of 65 international units per kilogram (IU/kg) turoctocog alfa 3 times per week. The planned treatment duration was for at least 12 months and up to a maximum period of 24 months. | 1 |
| Total | 1 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Turoctocog Alfa | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 0 Participants | — |
| Age, Categorical Between 18 and 65 years | 1 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 0 Participants | — |
| Sex: Female, Male Male | 1 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 1 |
| other Total, other adverse events | 1 / 1 |
| serious Total, serious adverse events | 0 / 1 |
Outcome results
Primary
Number of Adverse Events
An adverse event (AE) was any untoward medical occurrence in a participant administered a medicinal product, and which does not necessarily have a causal relationship with this treatment.
Time frame: Month 0 - up to month 12
Population: Safety analysis set (SAS) comprised of the participant(s) who initiated ITI treatment with turoctocog alfa.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Turoctocog Alfa | Number of Adverse Events | 6 Adverse events |
Secondary
Response to FVIII ITI Treatment (Success, Partial Success, Failure, Other)
ITI treatment response was categorized as: 1. Success: Undetectable inhibitor titre \<0.6 bethesda units (BU) (or lower limit of quantification \[LLoQ\] if above 0.6 BU); Normalised FVIII in vivo recovery, defined as ≥0.013 international units (IU) per milliliter per IU per kilogram ((IU/ml)/(IU/kg)) (66% of expected incremental recovery); turoctocog alfa half-life ≥7 hours (based on FVIII activity) after 72 hours treatment-free washout period. 2. Partial success: Inhibitor titre ≤5 BU; Clinical effect of turoctocog alfa therapy as judged by the investigator. 3. Failure (one criterion had to be fulfilled): Failure to attain defined success or partial success after 24 months of ITI treatment with turoctocog alfa; Decrease in inhibitor titre after 12 months of ITI treatment \<20% compared to peak titre. 4. Other: Participants not fulfilling the above criteria e.g. early withdrawal from ITI treatment, lack of adherence to recommended ITI protocol etc.
Time frame: Month 12
Population: FAS comprised of the participant(s) who initiated ITI treatment with turoctocog alfa.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Turoctocog Alfa | Response to FVIII ITI Treatment (Success, Partial Success, Failure, Other) | Success | 0 Participants |
| Turoctocog Alfa | Response to FVIII ITI Treatment (Success, Partial Success, Failure, Other) | Partial success | 0 Participants |
| Turoctocog Alfa | Response to FVIII ITI Treatment (Success, Partial Success, Failure, Other) | Failure | 0 Participants |
| Turoctocog Alfa | Response to FVIII ITI Treatment (Success, Partial Success, Failure, Other) | Other | 1 Participants |