A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a Single Dose of NM8074 Administered Intravenously to Healthy Subjects
概览
- 阶段
- 1 期
- 干预措施
- NM8074
- 疾病 / 适应症
- Healthy
- 发起方
- NovelMed Therapeutics
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Monitoring of Adverse Events (AEs) and Serious Adverse Events (SAEs)
- 状态
- 已完成
- 最后更新
- 3年前
概览
简要总结
This is a Phase 1 randomized, double-blind, placebo-controlled, single administration, sequential cohort with sentinel dosing, dose escalation study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of NM8074 in healthy subjects. This study will include 5 cohorts, with each cohort consisting of a total of 8 healthy subjects, including both males and females, randomized in a 3:1 ratio of NM8074 to placebo (6 subjects assigned to NM8074 and 2 subjects assigned to placebo).
详细描述
NM8074 is a novel, recombinant, humanized monoclonal antibody. NM8074 selectively binds to human Factor Bb with high affinity and blocks the formation of Alternative Pathway (AP) driven C3 and C5 convertases. Both C3 and C5 convertases are critical for exacerbation and amplification of the AP in complement-mediated disorders. 06-101-FIH-NM8074 is the first-in-human clinical trial for NM8074 which is intended to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of NM8074 when delivered as a single intravenous infusion to healthy volunteers. Doses will be escalated in each of the 5 sequential cohorts using sentinel dosing.
研究者
入排标准
入选标准
- •Male or Female subjects ≥18 years to ≤60 years of age, inclusive
- •Body mass index (BMI) between 18 kg/m2 and 32 kg/m2, inclusive and weigh at least 50 kg
- •QT interval (Fridericia's correction \[QTcF\]); QTcF ≤ 450 msec for males and ≤ 470 msec for females at Screening and prior to dosing on Admittance Day -1
- •Willing and able to give signed Informed Consent and comply with the study visit schedule
- •In good general health as determined by the Investigator's review of medical history, concomitant medications, physical examination, clinical laboratory tests, and ECG evaluations
- •Male subjects must agree to use barrier contraception (male condom) and not donate sperm during the treatment period and for at least 3 months after the last dose of NM
- •Barrier contraception is required even with documented medical assessment of the surgical success of a vasectomy
- •Female subjects who are of childbearing potential must use highly effective contraception1 or acceptable contraception as defined below, starting at screening and continuing until at least 3 months after the last dose of NM
- •Female subjects must not donate ova during the screening and treatment periods and for at least 3 months after the last dose of NM8074
- •Highly effective contraceptive methods for female subjects are as follows:
排除标准
- •Subjects who plan to travel during the course of the study to endemic areas as per the Centers for Disease Control and Prevention (CDC) definition for meningococcal meningitis
- •Has a currently active systemic infection that requires antibiotic, antifungal, antiparasitic, or antiviral medications. Any infection prior to entry into the study must have been cured for 1 month prior to the Screening Visit
- •Positive QuantiFERON®-TB test indicating possible tuberculosis (TB) infection, active systemic bacterial, viral, or fungal infection within 14 days prior to dosing
- •Has a known history of meningococcal/pneumococcal/gonococcal disease
- •Contraindication to receiving meningococcal vaccine, including severe (life-threatening) allergic reaction to a previous dose of meningococcal serogroup B vaccine; severe (life-threatening) allergy to any vaccine component; previous diagnosis of Guillain-Barré Syndrome
- •History of unexplained, recurrent infection; or infection requiring treatment with systemic antibiotics within the last 90 days prior to dosing
- •History of latent or active tuberculosis or exposure to endemic areas within 8 weeks prior to the tuberculosis test performed at screening
- •Clinically significant abnormalities in urine upon urinalysis to allow investigator discretion and to prevent disqualifications for minor findings of no significance such as mucus in the urine
- •Any of the following hematology tests: hemoglobin; total white blood cells (total WBC); absolute neutrophils; and platelets outside the laboratory reference range at Screening and Day -1
- •Abnormal urine tests: Clinically significant abnormalities in urine upon urinalysis" to allow investigator discretion and to prevent disqualifications for minor findings of no significance such as mucus in the urine
研究组 & 干预措施
NM8074
6 subjects per each of the 5 cohorts will receive a single dose of NM8074 administered via IV (intravenous) infusion at 0.3, 1.0, 3.0, 10, or 20 mg/kg
干预措施: NM8074
Placebo
2 subjects per each of the 5 cohorts will receive saline placebo administered via IV infusion.
干预措施: Placebo
结局指标
主要结局
Monitoring of Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Up to 71 days post-dose
Adverse events will be graded according to the CTCAE v4.03. If the AE term is not described in the grading scales, the AE severity shall be reported according to the following: * Grade I: Mild (awareness of sign or symptom, but easily tolerated) * Grade II: Moderate (discomfort sufficient to cause interference with normal activities) * Grade III: Severe (incapacitating, with inability to perform normal activities) * Grade IV: Life threatening * Grade V: Fatal
次要结局
- Area under the serum concentration versus time curve from time zero to the last quantifiable concentration (AUCt)(Up to 71 days post-dose)
- Terminal elimination rate constant (λz)(Up to 71 days post-dose)
- Total clearance (CL)(Up to 71 days post-dose)
- Time to maximum observed serum concentration (tmax)(Up to 71 days post-dose)
- AUC from time zero to infinity (AUC∞)(Up to 71 days post-dose)
- Maximum observed serum concentration (Cmax)(Up to 71 days post-dose)
- Volume of distribution (Vd)(Up to 71 days post-dose)
- Change from Baseline or Percent Change from Baseline in Levels of Complement Component C3b via Alternative Pathway (AP) of Complement Activity(Up to 71 days post-dose)
- Number of Participants with Antidrug Antibodies (ADAs) to NM8074(Up to 71 days post-dose)
- Terminal half-life (t½)(Up to 71 days post-dose)
- Change from Baseline or Percent Change from Baseline in Levels of Membrane Attack Complex (MAC) via the Alternative Pathway (AP) of Complement Activity(Up to 71 days post-dose)