A Study of Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of SR604 in Two Participants Groups (Part A: Healthy Participants, and Part B: Participants With Hemophilia A or Hemophilia B)

Launched by EQUILIBRA BIOSCIENCE LLC · Apr 3, 2024

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment called SR604 to see how safe it is and how well it works for people with severe Hemophilia A or Hemophilia B, as well as healthy participants. The trial has two parts: Part A includes healthy men aged 18 to 65, while Part B focuses on men with severe bleeding disorders. Participants in Part B must have a history of bleeding events and may need to pause their current treatment to join the study.

If you or a loved one is interested in participating, the study is currently looking for men between the ages of 18 and 65 who meet specific health criteria, such as having a normal weight and no major health issues. Participants can expect to receive the study medication, undergo various health checks, and provide information about their health during the trial. It's important to note that sexually active men will need to use effective birth control during the study and for 90 days afterward. Overall, this trial aims to better understand SR604’s effects and help improve treatment options for people with Hemophilia.

Gender

MALE

Eligibility criteria

• Key Inclusion Criteria:
• Part A:
• • Body mass index between 18 and 30 kilograms per meter square (kg/m\^2), inclusive, and weighs greater than or equal to (\>=) 50 kilograms (kg), less than or equal to (\<=) 90 kg.
• • No clinically significant findings on medical examination, including physical examination, 12-lead electrocardiogram, and clinical laboratory tests.
• • Sexually active men must commit to use an effective method of birth control while taking the study intervention and for 90 days after the dose of study intervention.
• Part B:
• • Participants must have one of the following bleeding disorders: Severe congenital Hemophilia A and Severe and/or moderately severe congenital Hemophilia B.
• • Participants whose bleeding is not well controlled on their current treatment regimen.
• • Medical records documenting a minimum of 2 years of bleeding event history.
• • Willing to undergo a weaning period from prior Hemophilia A or Hemophilia B treatment or prophylaxis.
• • Sexually active men must commit to use an effective method of birth control while taking the study intervention and for 90 days after the dose of study intervention.
• Key Exclusion Criteria:
• Part A:
• • Participant has clinically significant history or evidence of cardiovascular, respiratory (including all chronic lung diseases), hepatic, renal, gastrointestinal, endocrine, neurological, immunological, bleeding, or psychiatric disorder(s).
• • Participant has a mean pulse less than (\<) 40 or greater than (\>) 90 beats per minute (bpm), mean systolic blod pressure (BP) \< 90 millimeter of mercury (mmHg) or \> 140 mmHg, or mean diastolic BP \< 50 mmHg or \> 90 mmHg at the screening visit.
• • Participant has a mean corrected QT corrected for heart rate by Fridericia's formula (QTcF) of \> 450 msec at the Screening Visit.
• • Participant has had injury, trauma, and/or major surgery within 3 months before Screening, or is planned to undergo surgery during the study.
• • Participant has received vaccination within 14 days before the dose of study intervention or has a vaccination planned during the study.
• * History of one or more of the following in participants and/or family members:
• • 1. Factor V (FV) Leiden mutation.
• • 2. Activated protein C (APC) resistant.
• • 3. Protein C (PC) or protein S (PS) deficiency.
• • 4. Prothrombin 20210 mutation;
• • 5. Antithrombin III (ATIII) deficiency.
• • History of clinically significant intracranial hemorrhage, pneumonia, chronic liver disease, liver or kidney transplants, or malignant diseases.
• • Any medical condition (eg, diabetes, obesity.) which, in the Investigator's opinion, could compromise participant safety, interfere with study intervention metabolism, or put the study outcome at undue risk. Any condition for which, in the opinion of the Investigator, participation would not be in the best interest of the participant or could prevent, limit or confound protocol-specified assessments.
• • Participants with a history of all types of thrombosis, including any arterial and/or venous thrombosis, superficial thrombophlebitis, or embolism. Additionally, participants with a history of thrombotic microangiopathy, stroke, and transient ischemic attack (TIA), or abnormal findings in any prior laboratory thrombophilia evaluation will be excluded.
• Part B:
• • Participants with a history of all types of thrombosis, including any arterial and/or venous thrombosis, superficial thrombophlebitis, or embolism. Additionally, participants with a history of thrombotic microangiopathy, stroke, and TIA, or abnormal findings in any prior laboratory thrombophilia evaluation will be excluded.
• * History of one or more of the following in participants and/or family members:
• • 1. FV Leiden mutation.
• • 2. APC resistant.
• • 3. PC or PS deficiency.
• • 4. Prothrombin 20210 mutation.
• • 5. ATIII deficiency.
• * Impaired cardiac function or clinically significant cardiac disease, including any of the following:
• • 1. Clinically significant and/or uncontrolled heart disease such as congestive heart failure requiring treatment (New York Heart Association Grade \>=2), left ventricular ejection fraction \< 50% as determined by multiple gated acquisition or echocardiogram, or clinically significant arrhythmia.
• • 2. QTcF \> 450 ms ECG or congenital Long QT Syndrome at the Screening Visit.
• • 3. Acute myocardial infarction or unstable angina pectoris \< 3 months prior to study entry.
• • Uncontrolled hypertension (systolic BP \> 150 mmHg and diastolic BP \> 100 mmHg), a history of hypertension crisis, or a history of hypertensive encephalopathy.
• * Participant with the following laboratory abnormalities:
• • 1. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 1.5 × upper limit of normal (ULN);
• • 2. Total bilirubin ˃3.0 × ULN and direct bilirubin ˃1.5 × ULN (unless due to Gilbert's syndrome).
• • Calculated creatinine clearance ˂ 60 mL/min using the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula at the Screening Visit.
• • Participant has positive test result for human immunodeficiency virus (HIV) antibody. a) If participants test positive for hepatitis B core antibody (HBcAb), additional tests including hepatitis B surface antibody, hepatitis B surface antigen (HBsAg), and hepatitis B viral deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) will be conducted to determine if there is an active infection. Participants with active infection will be excluded from the study.; b) Participants who test positive for hepatitis C virus antibody will be required to have a negative result for hepatitis C viral ribonucleic acid (RNA) PCR before enrollment. Individuals with positive results for hepatitis C PCR will be excluded from the study.
• • Chronic liver disease (Child-Pugh class C hepatic impairment), or history of liver or kidney transplants.
• • Injury, trauma, and/or major surgery (mediastinoscopy, insertion of a central venous access device, and insertion of a feeding tube are not considered major surgery), major dental procedures (extractions, etc.) within 4 weeks of the first dose of SR604 or planned surgery during the study.
• • Active infection requiring systemic antibiotic or antiviral therapy or in a sepsis condition within 14 days prior to the first dose of SR604.
• • Any medical condition (eg, diabetes, obesity) which, in the Investigator's opinion, could compromise participant safety, interfere with SR604 metabolism, or put the study outcome at undue risk.