Clinical Effectiveness of Egg-derived Polyclonal Antibodies (IM-01) for the Treatment of Mild-moderate Clostridium Difficile Infection (CDI)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Reduce C. difficile pathogen count, spore count, and C. difficile Toxin Titers in stool samples following IM-01 treatment,
研究概览
简要总结
Patients diagnosed to have mild-moderate CDI will be randomized to receive IM-01 egg-derived anti-C. difficile polyclonal antibodies in increasing dosages, twice daily, for a total of 10 - 14 days. Resolution of diarrhea and other symptoms and fecal test parameters will be used to assess clinical effectiveness of Immunotherapy with IM-01 antibodies. Patients will be followed for recurrence of CDI. Subjects who are assessed as non-respondents to IM-01 will be reassessed and treated with standard of care CDI antibiotics for 10 -14 days.
详细描述
INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE The increased incidence of antibiotic resistant 'superbugs' has amplified the use of broad spectrum antibiotics worldwide. An unintended consequence of antimicrobial treatment is disruption of gastrointestinal microbiota, resulting in susceptibility to opportunistic pathogens, such as Clostridium difficile (C. difficile).
C. difficile is a gram-positive, spore-forming, anaerobic bacterium that causes hospital and community-acquired enteric infections resulting in C. difficile-associated diarrhea, pseudo membranous colitis, colitis and death.
Clostridium difficile infection (CDI) remains the predominant cause of health care -associated infectious diarrhea, centered mainly in hospitals but also in the community at a rate of ~100/100,000 population and affecting the elderly disproportionately. Antimicrobial damage to the intestinal microbiome combined with the acquisition of spores of C. difficile is the main cause of pathogenesis. CDI is endemic in hospitals, and although infection control measures have reduced nosocomial rates of CDI in Canada over the past 5 years, community cases now appear to be more apparent .Treatment of CDI utilizes alternate antimicrobials directed at the pathogen, mainly metronidazole, vancomycin, or fidaxomicin given for a recommended 10-14 days. While the majority respond to antibiotic treatment, subsequent recurrences of CDI are observed in 25-40% of patients. Recurrences of CDI are retreated with the same antibiotics and due to the non-selective spectrum of activity of metronidazole and vancomycin, recurrences are increasing in probabilities for subsequent recurrences. Fidaxomicin is relatively more selective and its use is associated with reduced recurrences, but the high cost of fidaxomicin has restricted the usage.
C. difficile infection is a serious diarrheal illness associated with substantial morbidity and mortality and is responsible for hospital and community-acquired diarrhea, pseudo membranous colitis colitis and death..
ImmuniMed Inc. has developed an oral Immunotherapy using egg-derived anti- C. difficile polyclonal antibodies (IM-01), that directly targets the virulence factors of C. difficile. IM-01 is produced from chicken eggs following the immunization of laying hens with C. difficile virulent antigens, C. difficile toxin A, toxin B, C. difficile whole cells and C. difficile spores. IM-01 is in the form of spray-dried whole egg powder (yolk plus egg white containing ovalbumin) and is very stable for functional activity. Upon reconstitution, IM-01 is administered orally, which allows it to reach to the intestinal lumen, where C. difficile toxins exert their toxic effects. In addition, IM-01 antibodies bind to C. difficile toxins and spores and neutralize their biological activities in vitro.
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
- None
盲法说明
Patients will be randomized 1:1 to receive IM-01 treatment dosage at 20g or 10g twice a day
入排标准
- 年龄范围
- 18 Years 至 89 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- •Provide signed and dated informed consent form
- •Willing to comply with all study procedures and be available for the duration of the study
- •Male or female, aged 18 to 89
- •In good general health as evidenced by medical history or Diagnosed with specific condition/disease or Exhibits specific clinical signs or symptoms or physical/oral examination findings
- •Participant has a diagnosis of CDI defined as (i) presence of diarrhea with 4 or more unformed stools within 24 hours and (ii) positive test for toxigenic C. difficile from stools collected within 7 days.
- •Participants received < 24 h of SOC therapy for CDI.
- •Participants presented with primary CDI episode or any number of CDI relapse recurrence of CDI
- •Participants comply with the eligibility criteria and willing to participate in the study including the 8 week post treatment follow up period.
- •White Blood Cell absolute neutrophil count <15 x 109/L,
- •Women of reproductive potential must use highly effective contraception. For those with child bearing potential, the following methods of birth control are required from Visit 1 up to at least 30 days after study treatment discontinuation: 1). Diaphragm, female condom or cervical cap, partner's use of a condom, any of which must be used in combination with a spermicide; 2). Intra-uterine device; 3). Oral or injectable contraceptive agent, implant, or transdermal contraceptive hormone patches. If a hormonal contraceptive is used, it must have been taken for at least one month prior to enrolment/randomization; 4). Sterilization method (tubal ligation/occlusion, or partner's vasectomy); 5). True abstinence from intercourse with a male partner only when this is in line with the preferred lifestyle of the subject.
- •Men of reproductive potential must use condoms-
排除标准
- •An individual who meets any of the following criteria will be excluded from participation in this study:
- •known allergic reactions to chicken egg components.
- •Female of child bearing potential and not receiving contraception; pregnant or lactating persons.
- •severe CDI defined as >10 unformed bowel movements (UBMs)/24 h period, fever >38.5 o C, White Blood Cell count > 15 x 109/L, abdominal pain and tenderness on physical examination, toxic megacolon, ileus, nausea, vomiting.
- •receipt of > 24 h of SOC treatment of CDI, or fecal microbial transplant (FMT) prior to enrollment.
- •treatment with another investigational drug or other intervention within 30 days prior to enrollment including intravenous immunoglobulin (IVIG) or monoclonal intravenous (IV) antibody.
- •received vaccine for C. difficile.
- •concurrent use of probiotics of any type during treatment and follow up.
- •unable to discontinue use of opiates for diarrhea control.
- •co-infection with another gastrointestinal (GI) pathogen.
- •presence of Inflammatory Bowel Disease (IBS), IBS with diarrhea (IBS-D), chronic diarrhea of unknown cause.
- •any condition that hinders oral consumption. Exception: nasogastric tubes can be used to administer the product.
- •death likely within study interval.
- •any circumstance or medical condition under the Investigator's opinion that precludes participation.
研究组 & 干预措施
Adults subjects with CDI receiving 20g a day
10 g twice a day for 10 - 14 days
干预措施: IM-01 (Drug)
Adults subjects with CDI receiving 40 g a day
20 g twice a day for 10 - 14 days
干预措施: IM-01 (Drug)
结局指标
主要结局
Reduce C. difficile pathogen count, spore count, and C. difficile Toxin Titers in stool samples following IM-01 treatment,
时间窗: day 56 IM-01 post-treatment
To enumerate numbers of C.difficile present per g of stool by dilution at plate counts on CCFA or Biomerieux C. difficile Chrom Agar , Total counts on three plates express as log 10 count /g versus spore counts after alcohol shock. Toxin titers: expressed as 1/dilution of the fecale filtrate neutralized by specific anti-toxin antibodies from Tech Lab using the CCNA test. .
Determine Clinical Response to IM-01 Treatment for CDI for 14 days
时间窗: 10-14 days of IM-01 post-treatment
Decrease the frequency of unformed bowel motions to less than 3 per day and sustain for the duration of treatment to 10-14 days.
次要结局
- Rate of recurrence of CDI in day 44, day 56 and day 70 IM-01 post-treatment follow up period(day 44, 56 and 70 post- IM-01 treatment)