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
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 8
- 主要终点
- Safety in Healthy Volunteers
研究概览
简要总结
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).
详细描述
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:
- Phase 1 - Randomized, double-blind, placebo-controlled, parallel group, single ascending dose (SAD) in HP with up to 5 dose cohorts.
- 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Masking is only applicable to Phase 1 in HP. Phase 2a is open label and there is no masking.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Phase 1- Placebo administered to HP
For each cohort in Phase 1 (SAD), 8 participants will be randomized in a 3:1 ratio; 6 participants to active (ADX-038): 2 participants to control (matched placebo). Randomization will be on Day 1. Initially, 2 sentinel participants (1 active and 1 placebo) will be randomized and dosed. The sentinel participants will be evaluated for safety. The investigator's assessment and the independent medical monitor will decide upon the randomization and dosing of the 6 remaining participants (5 active and 1 placebo) according to the randomization schedule.
干预措施: Placebo (Drug)
Phase 1 - Active ADX-038 administered to HP
For each cohort in Phase 1 (SAD), 8 participants will be randomized in a 3:1 ratio; 6 participants to active (ADX-038): 2 participants to control (matched placebo). Randomization will be on Day 1. Initially, 2 sentinel participants (1 active and 1 placebo) will be randomized and dosed. The sentinel participants will be evaluated for safety. The investigator's assessment and the independent medical monitor will decide upon the randomization and dosing of the 6 remaining participants (5 active and 1 placebo) according to the randomization schedule.
干预措施: ADX-038 (Drug)
Phase 2a - ADX-038 administered to PNH participants
This will be initiated at the dose level determined by the Safety Review Committee from SAD in HPs. The treatment of PNH participants is an open-label study.
干预措施: ADX-038 (Drug)
结局指标
主要结局
Safety in Healthy Volunteers
时间窗: 365 days
To evaluate the safety and tolerability of ADX-038 in HVs by incidence, relationship, and severity of adverse events and serious adverse events
Safety in Paroxysmal Nocturnal Hemoglobinuria Participants
时间窗: 365 days
Evaluate the safety and tolerability of ADX-038 by incidence, relationship, and treatment-emergent adverse events and serious adverse events.
次要结局
- Pharmacokinetics in Healthy Participants(8 days)
- Pharmacodynamics in Healthy Participants(365 days)
- Pharmacodynamics in Paraxysmal Nocturnal Hemoglobinuria(365 days)