Common adverse reactions ( ≥ 1% of subjects) reported in clinical trials were arthralgia and malaise.
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of one drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in practice.
In the multi-center, prospective, open-label, clinical trial of ELOCTATE, 164 adolescent and adult, previously treated patients (PTPs, exposed to a Factor VIII containing product for ≥ 150 exposure days) with severe Hemophilia A ( < 1% endogenous FVIII activity or a genetic mutation consistent with severe Hemophilia A) received at least one dose of ELOCTATE as part of either routine prophylaxis, on-demand treatment of bleeding episodes or perioperative management. A total of 146 (89%) subjects were treated for at least 26 weeks and 23 (14%) subjects were treated for at least 39 weeks.
Adverse reactions (ARs) (summarized in Table 3) were reported for nine (5.5 %) subjects treated with routine prophylaxis or episodic (on-demand) therapy.
Two subjects were withdrawn from study due to adverse reactions of rash and arthralgia. In the study, no inhibitors were detected and no events of anaphylaxis were reported.
Table 3: Adverse Reactions Reported for ELOCTATE (N=164)
|MedDRA System Organ Class||MedDRA Preferred Term||Number of Subjects n (%)|
|General disorders and administration site conditions||Malaise||2 (1.2)|
|Chest pain||1 (0.6)|
|Feeling cold||1 (0.6)|
|Feeling hot||1 (0.6)|
|Nervous systemdisorders||Dizziness||1 (0.6)|
|Joint swelling||1 (0.6)|
|Gastrointestinaldisorders||Abdominal pain, lower||1 (0.6)|
|Abdominal pain, upper||1 (0.6)|
|Vascular disorders||* Angiopathy||1 (0.6)|
|Cardiac disorders||Bradycardia||1 (0.6)|
|Injury, poisoning, and procedural complications||Procedural hypotension||1 (0.6)|
|Respiratory, thoracic, and mediastinal disorders||Cough||1 (0.6)|
|Skin and subcutaneous tissue disorders||Rash||1 (0.6)|
|*Investigator term: vascular pain after injection of study drug|
Clinical trial subjects were monitored for neutralizing antibodies to Factor VIII. No subjects developed confirmed, neutralizing antibodies to Factor VIII. One 25 year old subject had a transient, positive, neutralizing antibody of 0.73 BU at week 14, which was not confirmed upon repeat testing 18 days later and thereafter.
The detection of antibodies that are reactive to Factor VIII is highly dependent on many factors, including: the sensitivity and specificity of the assay, sample handling, timing of sample collection, concomitant medications and underlying disease.