Safety, Tolerability, PK and PD of ADX-038 in Healthy Participants and Paroxysmal Nocturnal Hemoglobinuria (PNH) Patients

Exclusion Criteria

• •History of any significant medical conditions, except for completely excised non-melanoma skin cancer or low grade cervical intraepithelial neoplasia without evidence of recurrence within the prior 3 months
• •Any viral, bacterial, parasitic, or fungal infection within the prior 30 days
• •Frequent respiratory, nasopharyngeal or ear infections (more than 5 infections per year)
• •History of environmental exposure or sick contact that increase the risk of meningococcal, pneumococcal and/or Haemophilus influenza type B infections
• •Complement deficiency or immunodeficiency syndrome
• •Major surgery or significant traumatic injury within the prior 3 months
• •History of anaphylaxis or hypersensitivity reactions
• •History of penicillin allergy
• •History of splenectomy
• •History of alcohol abuse or illicit drug use
• •Donated plasma within the prior 7 days
• •Donated blood or loss more than 400 milliliters of blood (excluding blood volume drawn at screening) within the prior 90 days
• •Screening estimated creatinine clearance of less than 60 milliliters per minute
• •Screening hematology, serum chemistry, or coagulation parameters that are outside the normal range
• •Screening vital signs that are abnormal per protocol specification
• •Screening electrocardiogram findings that are clinically significant
• •Pregnant or lactating females
• •Use of prescription (except for contraceptives and study-related prophylactic antibiotics) or over-the counter medications (except for paracetamol or ibuprofen) or vitamins/supplements within the prior 7 days
• •Use of medications that may reduce the effectiveness of hormonal contraceptives within the prior 28 days
• •Use of an investigational therapeutics within the prior 30 days or within the expected washout (at least 5 half-lives)
• •Unwilling or unable to adhere to study-related prophylactic antibiotics requirements
• •Any viral, bacterial, parasitic, or fungal infection within the prior 14 days
• •HIV, active hepatitis C or hepatitis B infection
• •History of meningococcal or tuberculosis infection
• •History of malignancy in the past 5 years, except for completely excised non-melanoma skin cancer or low grade cervical intraepithelial neoplasia with no evidence of recurrence within the prior 3 months
• •Complement deficiency syndrome
• •History of hematopoietic stem cell transplantation
• •History of splenectomy
• •Inflammatory bowel disease, systemic lupus erythematosus, rheumatoid arthritis, or chronic liver disease
• •Clinically significant and uncontrolled medical conditions including, but not limited to, thromboembolic disease, acute coronary syndrome, and diabetes
• •Pregnant or lactating females
• •Use of an investigational therapeutics within the prior 30 days or within the expected washout period (at lest 5 half-lives)
• •Abstain from alcohol consumption for 48 hrs before day of dosing and restrict to no more than an average of 14 standard drinks per week