IGHID 11705 A Randomized, Open-label, Controlled Clinical Trial to Assess the Efficacy of F598 in Preventing an Experimental Urethral Infection With Neisseria Gonorrhoeae in Healthy Male Subjects
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Assess the efficacy of F598 in preventing an experimental urethral infection with N. gonorrhoeae
研究概览
简要总结
Approximately 24 healthy male volunteers between the ages of 18 and 35 years will be enrolled at a single center for a duration of two months for each subject. Subjects who meet the enrollment criteria will be randomized to one of four open-label groups: Control (no treatment) or treatment with F598 at one of three doses. Following F598 administration or assignment to the Control group, subjects must return to the study site for inoculation with N. gonorrhoeae within 2 weeks. Once subjects have been inoculated with N. gonorrhoeae, they will enter the observation phase and will return to the study site daily for up to 5 days. At the end of the observation phase, definitive antibiotic therapy will be administered. A follow-up visit will be conducted 3-5 days after definitive antibiotic and a confirmatory interaction will occur with the subjects 7-10 days after the follow-up to confirm the subject's response. A final visit will occur approximately 8 weeks after inoculation.
详细描述
The study is comprised of 8 phases:
- Screening (Visits 1 and 2)
- F598 administration (Visit 3)
- Inoculation (Visit 4)
- Observation (Visits 5 - 8, as needed)
- Definitive antibiotic treatment (Visit 9)
- Test of cure (Visit 10)
- Confirmatory interaction (Visit 11)
- Final pharmacokinetic (PK)/pharmacodynamic (PD)/anti-drug antibody determination (Visit 12)
For the purposes of standardization, Day 1 of the study will be considered the day of inoculation.
During the Screening phase, prospective subjects will undergo informed consent and will be reviewed for their compatibility with the eligibility criteria. Those subjects who meet all of the Inclusion criteria and none of the Exclusion criteria will be enrolled. Following enrollment, subjects must undergo a repeat urine screen for C. trachomatis, N. gonorrhoeae and T. vaginalis (Days -17 to -4).
If the second urine screening test is negative, subjects will enter the F598 administration phase. Subjects will return to the study site and will be randomized to one of four open-label groups: Control (no treatment) or treatment with F598 at one of three doses. Following F598 administration or assignment to the Control group, subjects must return to the study site for inoculation with N. gonorrhoeae within 2 weeks. Thus, F598 will be administered on any one of Days -12 to -2.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Prevention
- 盲法
- Single (Participant)
盲法说明
All doses of F598 will be administered on an open-label basis. Investigators will be unblinded, and subjects will be aware if they are randomized to the control group or one of the active dose groups; however, subjects in one of the active dose groups will not be informed of their randomized dosage.
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy male between the ages of 18 and 35 years
- •Able and willing to be located easily by providing street address and telephone number (land line and/or cell phone number)
- •Able and willing to provide written informed consent
- •Able and willing to attend all study visits and follow-up visit during the week after treatment
- •Willing to abstain from masturbation during the 6 days after inoculation
- •Willing to abstain from all sexual activity during the course of the study
- •No clinically significant abnormalities on physical examination
- •No clinically significant abnormalities in serum chemistries, hematology and urinalysis
- •Urine negative for chlamydia, gonorrhea and trichomonas
- •No history of sexually transmitted infections (STIs), including syphilis and hepatitis B (HBV) & hepatitis C (HCV)
- •Negative human immunodeficiency virus (HIV), syphilis and HCV serologies
- •Negative HBV core and surface antibodies or results consistent with immunization (negative HBV core antibody/positive HBV surface antibody)
- •No history of bleeding diathesis
- •No history of seizures (due to reports of seizures with ciprofloxacin)
- •No history of cancer, except basal cell carcinoma of the skin more than 5 years ago
- •No history of drug abuse
- •No history of psychiatric disorders, except depression controlled by medication
- •No history of genitourinary surgery
排除标准
- •Student or employee under the direct supervision of any of the study investigators
- •Any known immunodeficiencies including complement deficiency, antibody deficiency, chronic granulomatous disease or HIV infection
- •Sickle cell disease
- •Psychiatric disorders that would interfere with the ability of the subject to comply with the requirements of the protocol
- •Unstable depression (defined as receiving either <3 months of the same medication (and dose) or a decompensating event during the previous 3 months) or depression that, in the opinion of the investigator, will compromise the subject's ability to comply with protocol requirements
- •Heart murmur or heart disease
- •Anatomic abnormality of the urinary tract
- •Any antibiotic treatment in the past 30 days, or azithromycin in the past 60 days
- •Chemotherapy within the past year
- •Current steroid use, except for topical application
- •Allergy to penicillin, cephalosporins, ciprofloxacin or to lidocaine
- •Treatment with medications that are contraindicated with cefixime, ceftriaxone or ciprofloxacin and that cannot be withheld for the single doses given in this study.
- •Medications not permitted with cefixime or ceftriaxone include:
- •Probenecid
- •Diuretics such as furosemide
- •Aminoglycoside antibiotics
- •Chloramphenicol
- •Medications not permitted with ciprofloxacin include:
- •Tizanidine
- •Theophylline
- •Glyburide
- •Cyclosporine
- •Probenecid
- •Phenytoin
- •Methotrexate
- •Antacids, multivitamins, and other dietary supplements containing magnesium, calcium, aluminum, iron or zinc
- •Caffeine-containing medications
- •Sucralfate or didanosine chewable or buffered
- •Major organ dysfunction
- •Any significant pre-existing condition preventing full compliance with the study
- •Infection or any serious underlying medical condition that would impair the ability of the subject to receive protocol treatment
研究组 & 干预措施
1 mg/kg single infusion of F598
1 mg/kg single infusion of F598
干预措施: 1 mg/kg single infusion of F598 (Drug)
3 mg/kg single infusion of F598
3 mg/kg single infusion of F598
干预措施: 3 mg/kg single infusion of F598 (Drug)
10 mg/kg single infusion of F598
10 mg/kg single infusion of F598
干预措施: 10 mg/kg single infusion of F598 (Drug)
结局指标
主要结局
Assess the efficacy of F598 in preventing an experimental urethral infection with N. gonorrhoeae
时间窗: Through study completion, an average of two months
Following the inoculation of N. gonorrhoeae, assess efficacy based of the proportion of infected subjects in each treatment group
次要结局
- Pharmacodynamics: Associations between the PD parameters and infection rate(Through study completion, an average of two months)
- Assess the impact of F598 on urethritis symptoms caused by N. gonorrhoeae infection(Up to 6 weeks)
- Incidence of Treatment-Emergent Adverse Events [Safety and Immunogenicity](Through study completion, an average of two months)
- Pharmacokinetic evaluation by measuring change from baseline in the concentration of F598 in the blood(Through study completion, an average of two months)