Long-term safety and efficacy of denecimig prophylaxis in participants with haemophilia A with or without factor VIII inhibitors

The primary objective is to investigate the long-term safety of Mim8 prophylaxis in participants with haemophilia A, with or without FVIII inhibitors. 4: 2: 5.

The secondary objectives include:

• Evaluation of the efficacy of Mim8 prophylaxis and the long-term efficacy of various prophylaxis regimens in participants with haemophilia A with or without inhibitors.
• Assessment of the device handling experience during administration via the DV3407-C1 pen-injector.

This clinical trial involves 18 participants diagnosed with haemophilia A, characterized by an intrinsic factor VIII level of less than 1%. The study population consists of both male and female patients, including a subgroup of infants under 1 year of age who are either previously untreated or minimally treated. Participants are selected based on a congenital diagnosis confirmed through medical records. Eligible individuals may include those transitioning from specific ongoing or completed clinical studies, provided they meet age-specific requirements. The cohort includes vulnerable populations, specifically infants, who require parental or legal representative consent. Inclusion is contingent upon the ability to comply with scheduled clinical visits and the maintenance of a diary.

This open-label study is designed as a phase 5 clinical trial to evaluate the long-term safety and efficacy of Mim8 prophylaxis in participants diagnosed with haemophilia A, including those with or without FVIII inhibitors. The research methodology involves monitoring participants from the initial screening phase through subsequent study visits. Primary efficacy and safety assessments, specifically the number of treatment-emergent adverse events, are conducted from the first visit at week 0 until the end-of-study visit, which may occur up to 283 weeks. Secondary endpoints, including the occurrence of anti-Mim8 antibodies, injection site reactions, and various types of bleeding episodes, are monitored from week 0 until the end of treatment, lasting up to 262 weeks. For specific cohorts, such as infants in Arm 3, the study assesses exposure and safety in previously untreated or minimally treated patients. The total duration of participant involvement is determined by the individual treatment course, which can extend up to approximately 283 weeks.

The experimental treatment consists of denecimig, which is provided as a solution for injection. This substance is administered via the subcutaneous route.

The efficacy and safety of Mim8 prophylaxis in participants with haemophilia A are evaluated through several parameters. Secondary efficacy endpoints include the assessment of treated bleeding episodes, categorized into spontaneous, traumatic, and joint bleeding episodes. For participants in Arm 2, the number of treated target joint bleeding episodes is specifically monitored. The occurrence of anti Mim8 antibodies and Mim8 plasma concentration are also measured as part of the clinical assessment.

Data collection for these parameters begins at Visit 1 (Week 0) and continues until the end of treatment, which extends up to 262 weeks. Additionally, device handling experience is evaluated using the Haemophilia Device Assessment Tool (HDAT) for participants assigned to Arm 2.