Evaluation of Safety Following Immune Tolerance Induction Treatment With Turoctocog Alfa in Patients With Haemophilia A Following Inhibitor Development in NN7170-4213 Trial

Study Overview
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Brief Summary
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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)

Official Title
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Evaluation of Safety Following Immune Tolerance Induction Treatment With Turoctocog Alfa in Patients With Haemophilia A Following Inhibitor Development in NN7170-4213 Trial

Conditions
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Haemophilia A

Intervention / Treatment
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* Drug: Turoctocog alfa


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Turoctocog alfa<br> | Drug: Turoctocog alfa<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Month 0 - up to month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Month 12 |