Nonacog Alfa Prophylaxis And Treatment Of Bleeding Episodes In Previously Treated Patients With Hemophilia B

Study Overview
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Brief Summary
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Nonacog alfa is indicated for the control and prevention of hemorrhagic episodes and for routine and surgical prophylaxis in patients with hemophilia B. The current single country, multi-centric, open label, non-randomized clinical trial is a post-approval study to fulfill the Central Drugs Standard Control Organization (CDSCO) request for supplementary information relating to the use of nonacog alfa in Indian subjects with hemophilia B.

Official Title
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A SINGLE COUNTRY, MULTICENTER, OPEN-LABEL AND NON-RANDOMIZED CLINICAL TRIAL WITH NONACOG ALFA PROPHYLAXIS AND TREATMENT OF BLEEDING EPISODES IN PREVIOUSLY TREATED PATIENTS WITH MODERATELY-SEVERE TO SEVERE HEMOPHILIA B FOR A DURATION OF 8 WEEKS.

Conditions
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Hemophilia B

Intervention / Treatment
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* Biological: Nonacog alfa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male subjects ≥12 years to ≤65 years with a diagnosis of congenital moderately-severe to severe hemophilia B (FIX activity ≤2%). Documented history of at least 50 exposure days (EDs) to FIX-containing products. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative, parent(s)/legal guardian) has been informed of all pertinent aspects of the study. For minors under the age of legal consent in India, assent of the participating child needs to be documented for the age range 12 to 18 in addition to the parental informed consent. Exclusion Criteria: Prior history of inhibitor to FIX or positive inhibitor testing (≥0.6 BU/mL) during Screening. Clinical signs or symptoms of decreased response to FIX. Known hypersensitivity to the active substance or any of the excipients. Known allergic reaction to hamster proteins. Presence of any bleeding disorder in addition to hemophilia B. Participation in other studies involving investigational drug(s) (Phases 1-4) within 30 days before the current study begins and/or during study participation. Planned surgery within 6 months from the start of the study. Unsuitable to participate in study for any other reason as assessed by the investigator; including any disorder, except for conditions associated with hemophilia B, which in the investigator's opinion might jeopardize subject's safety or compliance with the protocol. Subjects (or a legally acceptable representative) is not able to understand study documents and study procedure. Immunocompromised subjects due to human immunodeficiency virus (HIV) infection (defined as viral load above or equal to 100,000 copies/mL; and for HIV+ subjects: cluster of differentiation 4 positive (CD4+) lymphocyte count below or equal to 200/μL). HIV status and CD4+ lymphocyte count results may be obtained at screening or from available medical records; results must be not older than 6 months prior to screening. Subjects who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, subjects who have been previously enrolled into the study, or subjects who are Pfizer employees directly involved in the conduct of the study. Planned use of any non-study medication for treatment of hemophilia (eg, other factor replacement agents, bypassing agents, or non-factor treatments [such as anti-tissue factor pathway inhibitors]).

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 65 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: Treatment Arm<br>At least twenty five eligible male subjects will be enrolled in the treatment arm to receive Nonacog alfa until 16 exposure days (EDs) or a period of up to 8 weeks on treatment had occurred (whichever occurs first). | Biological: Nonacog alfa<br>* Nonacog alfa is indicated in India for the treatment and prophylaxis of bleeding in patients with hemophilia B (congenital factor IX deficiency).<br>* Other names: BeneFIX;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Developed Factor IX (FIX) Inhibitors | FIX inhibitor development was defined as an inhibitor titer >= 0.6 Bethesda units per milliliter (BU/mL) confirmed by central laboratory testing during the course of the study. | At Visit 4 (any 1 day between Day 52 to Day 60) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Serious Adverse Events (SAEs) and Medically Important Events (MIEs) | An adverse events (AE) is any untoward medical occurrence in clinical investigation participant administered a product or medical device; event need not necessarily to have a causal relationship with treatment or usage. SAEs: an AE resulting in any of following outcomes/deemed significant for any other reason: death; initial/prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. MIEs: any confirmed FIX inhibitor development (titer greater than or equal to 0.6 BU/mL confirmed by central laboratory testing), thrombotic events (any event associated with the formation of a blood clot including catheter-associated thrombi and thrombotic complications) or hypersensitivity reactions (hypersensitivity reaction to a FIX product with symptoms such as hives, urticaria, tightness of chest, wheezing, hypotension, and anaphylaxis based on investigator's judgment). | Baseline up to 28 days after last dose of study drug (i.e, up to 116 days) | 
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs are events between first dose of study drug and up to 116 days that were absent before treatment or that worsened relative to pretreatment state. | Baseline up to 28 days after last dose of study drug (i.e, up to 116 days) | 
| Mean Annualized Bleeding Rate (ABR) | ABR: number of bleeding episodes per year. ABR for each participant = number of bleeds during treatment interval duration (TID)/(TID/365.25). Number of bleeds for each participant for ABR included all new bleeds (with unique start date and time) requiring treatment with nonacog alfa during TID. TID=date of Visit 4 (3 to 10 days after last dose) - date of Visit 2 (Day 1) +1. For participants who had Visit 4 beyond 3 (+7) days after final dose due to COVID-19 pandemic, date of final dose was used in place of date of Visit 4. For discontinued participants, date of final dose/last study visit date (whichever occurred later) was used to replace Visit 4. | Up to 88 Days | 
| Mean Annualized Total Factor Consumption (TFC) Per Participant | The TFC per participant was the sum of the total amount (in international units [IU]) infused for each infusion for each participant. Annualized TFC of nonacog alfa was derived for each participant by using the following formula; Annualized TFC = (TFC / treatment interval duration)*365.25. Treatment interval duration was calculated as the number of days beginning on Visit 2 (Day 1, provided an infusion was given) up to Visit 4 (any 1 day between Day 52 to Day 60). | Up to 88 Days | 
| Mean Annualized Total Factor Consumption (TFC) by Weight Per Participant | The total amount in international units (IU) per kilogram infused for each infusion recorded were summed to calculate the total factor consumption for each participant. Annualized TFC = (TFC / treatment interval duration)*365.25. Treatment interval duration was calculated as Date of Visit 4 - Date of Visit 2 +1. If Date of Visit 4 - Last dosing date was > 10 days then Date of Visit 4 was replaced with Last dosing date. If Date of Visit 4 was missing (due to discontinuation or any other reason), then Date of Visit 4 was replaced with last dosing date or last subject visit date, whichever was greater. International unit per kilogram= IU/kg. | Up to 88 days | 
| Mean Number of Nonacog Alfa Infusions Used to Treat Each Bleed | Number of nonacog alfa infusions used to treat each bleed in participants was calculated by adding the initial (on-demand) infusion to any subsequent (on-demand) infusions for the same bleed (same bleed start date/time). On demand treatment was defined as treatment used to treat a bleeding episode. | Up to 88 days |