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

• Status: Not yet recruiting
• Trial end date: 2025-06-30
• Target enrollment: 0
• Participant gender: All

Summary

The first-in-human Phase 1 study described herein will evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of ADX-038 in both healthy volunteers (HV) and in patients with paroxysmal nocturnal hemoglobinuria (PNH).

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: ADARx Pharmaceuticals, Inc.
• Collaborator: ADARx Australia Pty Ltd

Criteria

Inclusion Criteria

1. Male and female adults 18 to 55 years old

2. Body mass index (BMI) between 18 and 32 kg/m2

3. Contraception use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies

4. Willing and able to provide informed consent and comply with all study visits and procedures

5. Negative urine drug, nicotine/tobacco, and breath alcohol test result

6. Neisseria meningitis vaccination

7. Pneumococcus vaccination

8. Hemophilus influenzae vaccination Exclusion Criteria

9. Any significant medical history

10. Active malignancy and/or history of malignancy in the past 5 years

11. History of liver disease, Gilbert's syndrome, or abnormal liver function test

12. Estimated creatinine clearance <60 mL/min using the Cockcroft-Gault formula

13. Any active infection or acute illness

14. History of meningococcal infection or frequent respiratory, nasopharyngeal or ear infections

15. History of previous or current tuberculosis infection.

16. Prior splenectomy

17. Major surgery or significant traumatic injury occurring within 3 months

18. Have any other conditions that, in the opinion of the Investigator or Sponsor, would make the participant unsuitable for inclusion

19. Positive serology tests for human immunodeficiency virus hepatitis B surface antigen or hepatitis C virus

20. Use of any prescription, vaccines, supplements/vitamins, or over-the counter medication

21. Treatment with another investigational product within 30 days

22. Known any clinically significant allergic reactions

23. Known hypersensitivity to any of the study drug ingredients or penicillin.

24. History or presence of alcohol

25. Blood donation

26. Pregnancy

27. May have a higher risk to be exposed to infected individuals, for example active healthcare employees.

Criteria (Part B) Inclusion Criteria

28. Male and female adults 18-65 years old

29. Confirmed diagnosis of PNH based on documented clone size of PNH blood cells by flow cytometry.

30. Serum LDH levels are at least 1.25-fold above the ULN for non-treated participants

31. Liver function test values are less than 2x ULN

32. Mean hemoglobin (Hb) <12 g/dL.

33. A history of red blood cell transfusion within at least 3 months

34. Body mass index (BMI) between 18 and 32 kg/m2, inclusive, at screening.

35. Contraception use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

36. Willing and able to provide informed consent and comply with all study visits and procedures

37. Neisseria meningitis vaccination

38. Pneumococcus vaccination

39. Hemophilus influenzae vaccination

Exclusion Criteria

40. Known or suspected hereditary or acquired complement deficiency

41. History of clinically significant arterial or venous thrombosis

42. History of hematopoietic stem cell transplantation

43. History of meningococcal infection

44. Any significant medical history

45. Active malignancy and/or history of malignancy in the past 5 years

46. Any active viral, bacterial, parasitic, or fungal infection or acute illness

47. Any evidence of sero-positive autoimmune connective tissue diseases

48. Any evidence of active inflammatory conditions

49. History of previous or current tuberculosis infection.

50. Prior splenectomy

51. Major surgery or significant traumatic injury occurring within 3 months

52. Have any other conditions that, in the opinion of the Investigator or Sponsor, would make the participant unsuitable for inclusion

53. Inadequate organ function

54. Positive serology tests for human immunodeficiency virus hepatitis B surface antigen or hepatitis C virus

55. Willing to continue after enrollment with their current treatment with a complement inhibitor.

56. Use of vaccines, or changes in any prescription, supplements/vitamins, or over-the counter medication

57. Treatment with another investigational product or biologic agent within 30 days

58. Blood donation within 30 days

59. Pregnancy