A Phase I-IIa Study of Safety, Tolerance, Pharmacokinetics, Dosimetry and Benefice of Early Nuclear Medicine Imaging of 99mTc-rhAnnexin V-128 in Patients With Rheumatoid Arthritis or Ankylosing Spondylitis
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAE) and Death
研究概览
简要总结
This was a monocentric, open label, Phase I-IIa study. Eligible patients who signed the ICF received two single intravenous (IV) bolus of the imaging agent 99mTc-rhAnnexin V-128. The first dose was administered on Day 1, and the second dose on Day 42 (±2 weeks).
All patients were to start a new disease modifying treatment for RA or AS on Day 2. This disease modifying treatment was at the discretion of the investigator and was not chosen by the sponsor.
Safety was monitored at every visit. Whole body scintigraphic imaging was performed at Day 1 and Day 42 after 99mTc-rhAnnexin V-128 dosing. Clinical disease assessments were performed at screening, Day 42 and Day 90 to assess response to RA or AS treatment. Blood was drawn to test for 99mTc-rhAnnexin V-128 immunogenicity at screening and on Days 30, 56 and 90. Patients participating in the pharmacokinetic (PK)/dosimetric sub-study had additional assessments in the 24 hours following the Day 1 dose of 99mTc-rhAnnexin V-128.
详细描述
The study was terminated early after the inclusion of 16 of the 20 planned patients. The sponsor decided to terminate the study earlier than planned due to slow accrual. Novartis acquired Advanced Accelerator Applications SA.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients diagnosed with RA based on ACR/EULAR 2010 criteria (score >=6), or Patients diagnosed with AS based on the ASAS criteria. Patients with RA must have serology assessment performed and documented at the time of enrollment.
- •Patient with RA active disease (DAS > 2,6) and the introduction of a Bi-DMARD should be indicated. RA patients must have been treated with DMARD (methotrexate, leflunomide and sulfasalazine) or combination of these treatments for at least 3 months. Treatment will be pursued while on study.
- •or RA patients must have been previously treated with Bi-DMARD before initiation of the new Bi-DMARD treatment. The non-response of the previous Bi-DMARD treatment must be documented.
- •or Patients with AS with insufficiently controlled disease while under NSAID and indication for Bi-DMARD. These patients must be under NSAID for at least 3 months and under the same NSAID for at least 1 month prior to enrollment.
- •≥ 18 years old
- •Karnofsky ≥ 80%
- •Negative Pregnancy test for women with childbearing potential
- •For women with childbearing potential, use of two reliable means of contraception (e.g., hormonal contraceptive, patch, vaginal ring, intrauterine device, associated with other barrier method of contraception such as the use of condoms) , throughout their participation in the study
- •Absence of ECG anomaly
- •written ICF signed
排除标准
- •Pregnancy or lactation
- •Liver impairment (ALT, AST or Bilirubin > 2 ULN) at screening visit or baseline
- •Kidney impairment (serum creatinine > 1.5 mg/dL)
- •History of congestive heart failure (NYHA III & IV)
- •History of malignant disease within 5 years
- •History of any disease or relevant physical or psychiatric condition or abnormal physical finding which may interfere with the study objectives at the investigator judgment
- •Known hypersensitivity to the investigational drug or any of its components
- •Participation to another clinical trial within 4 weeks before study inclusion except for patients who have participated or who are currently participating in an interventional study without any study drug administration.
研究组 & 干预措施
99mTc-rhAnnexin V-128, i.v.
Patients will receive 2 administrations of the 99mTc-rhAnnexin V-128 medical imaging agent: one at Day 1 and the other at Day 42.
干预措施: 99mTc-rhAnnexin V-128 (Drug)
结局指标
主要结局
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAE) and Death
时间窗: From screening up to Day 90
An adverse event (AE) is defined as any untoward medical occurrence in a patient and which does not necessarily have a causal relationship with the study medication. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease, temporally associated with the use of a study medication, whether or not causally related to the study medication. TEAEs are defined as all AEs reported after the first dose. An SAE is any untoward medical occurrence that at any dose: results in death, is life-threatening, life-threatening, results in persistent or significant disability/incapacity, results in congenital anomaly or birth defect, requires in-patient hospitalization or leads to prolongation of hospitalization.
次要结局
- Systemic Clearance (Cl) of 99mTc-rhAnnexin V-128(Day 1 (0 (Predose), 0.05, 0.10, 0.15, 0.30, 1.00, 1.50, 2.00, 4.00 and 24.00 hours))
- Area Under the Curve Extrapolated to Infinity (AUC) of 99mTc-rhAnnexin V-128(Day 1 (0 (Predose), 0.05, 0.10, 0.15, 0.30, 1.00, 1.50, 2.00, 4.00 and 24.00 hours))
- Distribution Volume (Vz) of 99mTc-rhAnnexin V-128(Day 1 (0 (Predose), 0.05, 0.10, 0.15, 0.30, 1.00, 1.50, 2.00, 4.00 and 24.00 hours))
- 99mTc-rhAnnexin V-128 Serum Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample)(Day 1 (0 (Predose), 0.05, 0.10, 0.15, 0.30, 1.00, 1.50 to 2.00, 3.00 to 4.00, 6.00 and 24.00 hours))
- Elimination Half-life (t1/2) of 99mTc-rhAnnexin V-128(Day 1 (0 (Predose), 0.05, 0.10, 0.15, 0.30, 1.00, 1.50, 2.00, 4.00 and 24.00 hours))
- Serum Concentration of rhAnnexin V-128 Based on Enzyme-linked Immunosorbent Assay (ELISA) Analysis(Day 1 (0 (Predose), 0.05, 0.10, 0.15, 0.30, 1.00, 1.50, 2.00, 3.00, 4.00, 6.00 and 24.00 hours))
- 99mTc-rhAnnexin V-128 Blood Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample)(Day 1 (0 (Predose), 0.05, 0.10, 0.15, 0.30, 1.00, 1.50 to 2.00, 3.00 to 4.00 and 24.00 hours))
- 99mTc-rhAnnexin V-128 Urine Cpm Decay Corrected Data (Counts Per Minute in 1 mL Sample)(Day 1 (0 (Predose), 1.00, 4.00, 6.00 and 24.00 hours))
- Number of Annexin Related Species as Assessed Size-Exclusion HPLC- High-Performance Liquid Chromatography (SEC-HPLC) Analysis(Day 1 (0 (Predose), up to 1.00 hour, from 1.00 to 4.00 hours, from 4.00 to 6.00 hours, from 16.00 to 24.00 hours))