NCT05082116 - Efficacy and Safety of Turoctocog Alfa Pegol (N8-GP) for Prophylaxis and Treatment of Bleeding Episodes in Previously Treated Chinese Patients With Haemophilia A (pathfinder10) | Crick

Eligibility

Sex: MALEMin age: 12 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial. * Male Chinese patient with severe congenital haemophilia A with a FVIII activity below 1% according to medical records. * Aged greater than or equal to 12 years at the time of signing informed consent. * History of at least 150 exposure days (EDs) to other FVIII products. * The patient and/or caregiver is capable of assessing a bleeding episode, keeping a diary, performing home treatment of bleeding episodes and otherwise following the trial procedures at the discretion of the investigator. Exclusion Criteria: * Known or suspected hypersensitivity to trial product or related products. * Previous participation in this trial. Participation is defined as signed informed consent. * Participation in any clinical trial of an approved or non-approved investigational medicinal product within 5 half-lives or 30 days from screening, whichever is longer. * Known history of FVIII inhibitors based on existing medical records, laboratory report reviews and patient and/or caregiver interviews. * Current FVIII inhibitors greater than or equal to 0.6 BU. * Congenital or acquired coagulation disorder other than haemophilia According to medical records. * HIV positive, defined by medical records, with CD4+ count less than or equal 200/L and a viral load greater than 200 particles/μl or greater than 400000 copies/mL within 6 months of the trial entry. If the data are not available in medical records within last 6 months, then the test must be performed at screening visit. * Previous significant thromboembolic events (e.g. myocardial infarction, cerebrovascular disease or deep venous thrombosis) as defined by available medical records. * Hepatic dysfunction defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) greater than 3 times limit of normal combined with total bilirubin greater than 1.5 times the upper limit of normal at screening, as defined by central laboratory * Renal impairment defined as estimated glomerular filtration rate (eGFR) below or equal to 30 mL/min/1.73 m\^2 for serum creatinine measured at screening, as defined by central laboratory. * Platelet count below 50×109/L at screening based on central laboratory values at screening. * Ongoing immune modulating or chemotherapeutic medication. * Any disorder, except for conditions associated with haemophilia A, which in the investigator's opinion might jeopardise the patient's safety or compliance with the protocol. * Mental incapacity, unwillingness or language barriers precluding adequate understanding or cooperation.

Outcomes

Primary Outcomes

Number of Bleeding Episodes Per Year (Annualised Bleeding Rate)

Number of bleeding episodes per year (Annualised Bleeding Rate) data is reported. Annualised bleeding rate (ABR) is the number of bleeding episodes per year.

Time frame: From start of treatment (Week 0) until Week 28

Secondary Outcomes

Haemostatic Effect of N8-GP When Used for Treatment of Bleeding Episodes, Assessed on a Four-point Scale for Haemostatic Response (Excellent, Good, Moderate and None)

Haemostatic effect of N8-GP for treatment of bleeding episodes was assessed by 4-point response scale: none, moderate, good or excellent. Evaluation during trial was done by participant and/or parent(s)/caregiver within approximately 8 hours after a single injection as follows: Excellent: Abrupt pain relief and/or clear improvement in objective signs of bleeding within approximately 8 hrs after a single injection; Good: Definite pain relief and/or improvement in signs of bleeding within approximately 8 hrs after a single injection, but possibly requiring more than one injection for complete resolution; Moderate: Probable or slight beneficial effect within approximately 8 hours after the first injection, but usually requiring more than one injection; None: No improvement, or worsening of symptoms.

Time frame: From start of treatment (Week 0) until Week 28

Number of Injections Needed to Treat Bleeding Episodes

The mean number of injections of N8-GP used for treatment of a bleed from start to stop of a bleed was reported.

Time frame: From start of treatment (Week 0) until Week 28

Consumption of N8-GP for Prophylaxis

The mean consumption of N8-GP for prophylaxis per year per participant was reported and it was measured in international units per kilogram per year (IU/kg/year).

Time frame: From start of treatment (Week 0) until Week 28

FVIII Trough Activity During Prophylaxis

Trough levels of FVIII was reported for all participnats who received prophylaxis treatment. Chromogenic assay was performed with N8-GP product specific standard (PSS) as a calibrator. The analysis is based on a mixed model on the log transformed plasma FVIII activity with age group as fixed effect and participant as a random effect. The mean trough is presented back-transformed to the natural scale.

Time frame: From start of treatment (Week 0) (excluding the first exposure) until Week 28

Percentage of Participants With Incidence Rate of Confirmed FVIII Inhibitors ≥0.6 BU

Percentage of participants who developed inhibitory antibodies against FVIII was presented. A participant was said to have FVIII-inhibitors if two consecutive tests, preferably within 2 weeks, were positive (greater than or equal to (≥) 0.6 bethesda unit (BU)). For the calculation of the inhibitor rate the numerator was included for all participants with neutralising antibodies while the denominator was included for all participants with a minimum of 50 exposures plus any participants with less than 50 exposures but with neutralising inhibitor.

Time frame: From start of treatment (Week 0) until Week 28

Number of Adverse Events (AEs)

An adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. All presented AEs are treatment-emergent. A treatment-emergent adverse event was defined as an event with onset after first N8-GP administration.

Time frame: From start of treatment (Week 0) until end of trial (Week 32)

Number of Serious Adverse Events (SAEs)

A serious adverse event (SAE) is defined as any untoward medical occurrence that at any dose results in death, or is life-threatening, or requires inpatient hospitalization or causes prolongation of existing hospitalization results in persistent or significant disability/incapacity, or may have caused a congenital anomaly/birth defect, or requires intervention to prevent permanent impairment or damage. All presented SAEs are treatment-emergent (any serious adverse events which occurred after trial product administration).

Time frame: From start of treatment (Week 0) until end of trial (Week 32)

Incremental Recovery (IR)

The incremental recovery was calculated by subtracting the FVIII activity (IU/mL) measured in plasma at time 0 from that measured at time 30 min after dosing and dividing this difference by the dose injected at time 0 expressed as IU/kg body weight. FVIII activity was measured with a chromogenic assay.

Time frame: 30 min post-injection at Week 0, Week 28

FVIII Activity 30 Min Post-injection (C30min)

FVIII plasma activity was measured after 30 mins of injection. FVIII activity was measured with a chromogenic assay.

Time frame: 30 min post-injection at Week 0, Week 28

FVIII Trough Activity 96 h Post-injection (C96h)

FVIII plasma activity was measured after 96 h of injection. This was measured at two time points Week 0 and Week 28 during the study. Chromogenic assay was performed.

Time frame: Single-dose: 96 h ± 8 h post-injection at Week 0, Steady-state: 96 h ± 8 h post-injection at Week 28

Area Under the Curve (AUC0-inf)

Area under the plasma activity versus time profile from time zero to infinity (AUC0-inf) was measured.

Time frame: 0-96 hours post-injection at Week 0 and Week 28

Area Under the Curve (0-t)

Area under the plasma activity versus time profile from time zero to last measurable activity (AUC0-t) was measured.

Time frame: 0-96 hours post-injection at Week 0 and Week 28

Area Under the Curve (0-96h)

Area under the plasma activity versus time profile from time zero to 96 hours (AUC0-96h) was measured.

Time frame: 0-96 hours post-injection at Week 0 and Week 28

Accumulation Ratio

Accumulation ratio was calculated as AUC(0-96h) at steady state/AUC(0-96h) at single dose. AUC(0-96) is the area under the plasma activity versus time profile from time zero to 96 hours.

Time frame: 0-96 hours post-injection on Week 28

Terminal Half-life (t½)

Terminal half life was calculated as ln(2)/λz; where λz is the terminal elimination rate constant. The terminal elimination rate constant was estimated using linear regression on the terminal part of the log (activity) versus time profile.