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

Phase 1 Key Inclusion Criteria

• 18 to 55 years of age

• Participants who are healthy as determined by medical evaluation

• History of recent meningococcal, pneumococcal and Haemophilus influenzae type B vaccinations or willing to be vaccinated

• Screening tests negative for illicit drug, nicotine, and alcohol use

Phase 1 Key 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

Phase 2a Key Inclusion Criteria

• at least 18 years of age

• Diagnosis of paroxysmal nocturnal hemoglobinuria based on documented clone size

• Hemoglobin concentration of less than 12 gram per deciliter

• History of recent meningococcal, pneumococcal and Haemophilus influenzae type b vaccinations or willing to be vaccinated

• On a stable anti-C5 regimen for greater than or equal to 12 weeks prior to Day 1

Phase 2a Key Exclusion Criteria

• 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