Brief Summary:
The first-in-human Phase 1/Phase 2a study described herein will evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of ADX-038 in both healthy participants (HP) and in patients with paroxysmal nocturnal hemoglobinuria (PNH).
Condition or disease
Paroxysmal Nocturnal Hemoglobinuria (PNH)
Intervention/treatment
ADX-038
Placebo
Detailed Description:
The clinical study described in this protocol is a Phase 1/Phase 2a study evaluating safety, tolerability, PK, and PD of ADX-038.
The study consists of 2 parts:
1. Phase 1 - Randomized, double-blind, placebo-controlled, parallel group, single ascending dose (SAD) in HP with up to 5 dose cohorts.
2. Phase 2a - Open label, single-arm (ADX-038), 2 dose study in participants with paroxysmal nocturnal hemoglobinuria (PNH) and residual anemia on a standard-of-care (SOC) anti-C5 regimen of ravulizumab or eculizumab.
| Study Type : |
INTERVENTIONAL |
| Estimated Enrollment : |
50 participants |
| Masking : |
TRIPLE |
| Masking Description : |
Masking is only applicable to Phase 1 in HP. Phase 2a is open label and there is no masking. |
| Primary Purpose : |
TREATMENT |
| Official Title : |
A Phase 1, Randomized, Double Blind, Placebo-Controlled, Single Ascending Dose Study in Healthy Participants Followed by a Phase 2a Open Label Study in Participants with PNH and Residual Anemia to Evaluate the Safety, Tolerability, PK and PD of ADX-038 |
| Actual Study Start Date : |
2023-08-07 |
| Estimated Primary Completion Date : |
2026-03-30 |
| Estimated Study Completion Date : |
2026-09-30 |
Information not available for Arms and Intervention/treatment
| Ages Eligible for Study: |
18 Years
|
| Sexes Eligible for Study: |
ALL |
| Accepts Healthy Volunteers: |
1 |
Criteria
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 usePhase 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 requirementsPhase 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 1Phase 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