Premature infants can get a serious inflammatory condition, called necrotizing enterocolitis (NEC), that damages parts of the intestines. It is the most common cause of illness of the intestinal tract in premature infants in the first few weeks of life. It is a very serious condition that can lead to death in up to half of affected infants. There is no way to predict whether an infant will get NEC, and there are no reliable early warning signals. There is no established preventive treatment for NEC. Infants with NEC are usually treated with bowel rest (stopping feeding by mouth), antibiotic medicines, and in some cases with surgery where the affected bowel needs to be removed.
Some studies have shown that live bacteria given to the intestine of premature infants as early as possible in their life might be able to prevent NEC. Researchers want to find out if an investigational drug called “IBP-9414”, which is made of living bacteria, can help prevent NEC in prematurely born infants. An investigational drug is a drug that is being tested and is not approved for use and sale by any authorities (like the U.S Food and Drug Administration [FDA], the European Medicines Agency [EMA], or the authority in your country
All infants in the study will receive “standard-of-care” treatment, which means they will receive the same medical treatment they would receive if they were not in the study. In addition to the standard-of-care treatment that all infants will receive, half of the infants in the study will receive the investigational drug (IBP-9414) and half will receive an inactive substance (contains no medicine) called “placebo”. Receiving placebo is the same as not receiving any medication other than the standard-of-care treatment. The reason placebo is used in this study is to help the researchers know if any effects they see in the study are because of the investigational drug rather than the researchers’ expectations about the effects of the study drug. Neither you nor the study doctor/staff will be able to choose or to know whether your child receives IBP 9414 or placebo. This is why the study is called “double blind”. Your child will be assigned at random (like flipping a coin) to receive IBP 9414 or placebo. Your child’s chances of receiving IBP 9414 or placebo are the same (50 50 chance). In case of medical need, the study doctor will be able to find out whether your child is receiving IBP 9414 or placebo. In this study, the placebo will be sterile water. Please ask the study doctor or study staff if you have any questions about your child receiving placebo.
The main purpose of this study is to see if IBP-9414 can prevent NEC and if it is safe and tolerable. The unit that doses of live bacterial drugs are measured in is called “colony forming units” or CFUs. The dose of IBP-9414 to be tested is 1x109 CFU, which means it contains 1 billion live bacteria. This dose has been tested previously in a smaller study of IBP-9414 and was found to be safe and tolerable. In order to see if this dose actually can prevent NEC, a much larger study involving more infants is needed.
It is planned that 2158 premature infants will be included in this study, who will be less than 48 hours old at the time they begin taking part. At the end of the study, the researchers will compare the infants who received IBP 9414 with those who received placebo, to help decide if receiving IBP 9414 can prevent NEC and if it is safe for premature infants.
While the study doctor responsible for your child will monitor the safety of your individual infant, the safety of all infants in the study, as well as the effect of IBP 9414, will also be monitored on an ongoing basis throughout the study by a so-called Data Monitoring Committee (DMC). A DMC is a panel of experts who are independent from the study team and the pharmaceutical company developing IBP 9414.
Most of the infants (1942) in the study will weigh up to 1000 grams birth weight (about 2 lbs) and the rest (216) will weigh 1001 to 1500 grams (about 2 lbs to about 3 lbs).
The study will start with a group of 300 infants, all of whom will be in the intermediate weight category (750-1000 grams category). After 300 infants have completed treatment, a panel of experts (called a Data Monitoring Committee or DMC), who know which treatment each infant received, will determine if IBP-9414 appears to be safe and well tolerated. Enrollment in the study will continue during this review.
Based on the DMC recommendation, enrollment will open to infants from the lower weight category (500 749 grams), alongside the intermediate weight category (750 1000 grams).
A second DMC safety review will occur after the first 600 infants have completed treatment. Enrollment in the study will continue during this review.
A third DMC safety review will be performed after 1400 infants have completed treatment. Enrollment in the study will continue during this review.
After 1400 infants, the plan is to open recruitment to infants in the higher birth weight category (1001 1500 grams). The study will continue with all 3 birth weight categories until 2158 infants have been enrolled
- Gestational age at birth of 23 weeks + 0 days -32 weeks + 0 days
- Birth weight 500-1500g. (First infants with birth weights 750-1000g will be included.After a DMC recommendation, infants with birth weights 500-1000g will then beincluded. After 1400 subjects in the study, infants with birth weights 500-1500g will then be included.)
- ≤ 48 hours of age
- Participation in any other interventional clinical trial
- Infants in extremis to whom no further intensive care is offered by attending neonatologist (e.g., infant being provided only hospice/comfort care)
- Infants with, or at a high probability for, early onset sepsis (positive blood cultures or with clinical/histological chorioamnionitis (according to Higgins et al, 2016), and with the expectation of empirical antimicrobial therapy for > five days)
The participation will last until the baby reaches a post-menstrual age of about 40 weeks (± 7 days), when the last study visit will be scheduled (follow-up visit). The post menstrual age is obtained by adding a child’s age (weeks since birth) to their gestational age at the time they were born.
If the child has been discharged from the hospital at the time the follow-up is scheduled, parents will be asked to return to the hospital/follow up clinic for the follow up visit. If parents are unable to return to the hospital/follow up clinic, the study staff will call them at home to ask for information about your child’s health.
Before a child can start the study, the study doctor or study staff will talk to parents about the study. Then they have to sign this form before the study doctor or study staff can begin the screening period to see if the child qualifies to be in the study.
If the child qualifies for the study, an experienced study staff member/study doctor will give to the child IBP-9414 or placebo (contains no medicine) in addition to standard care once a day. The treatment will be started before the child reaches the age of 48 hours after birth and will continue until the child reaches a post-menstrual age of about 35 weeks. The treatment can be discontinued earlier if the study doctor thinks that it is in the best interest of the child.
IBP 9414 is a freeze-dried powder that will be dissolved in sterile water before it is administered. Infants who receive placebo will get the sterile water only, with no IBP-9414. IBP-9414 or placebo will be given to the infants through a feeding tube that passes through the nose or mouth, if a feeding tube is being used, or directly into the mouth if no feeding tube is being used.
The study doctor or study staff will do the things listed below at different times during the study. If you would like more information about which tests and procedures will be done and at what times, ask the study doctor or study staff. Many of these are routine care and are done daily.
parents may be asked questions about them and their child’s medical history, and the method of delivery.
Demographic data (gender, race, ethnicity, exact time and date of birth – gestational age) will be recorded.
Any medications that have been given to the child will be recorded.
The study doctor will record the so-called “APGAR” score of the baby. This is a score that summarizes the health of any newborn child. It includes Appearance, Pulse, Grimace, Activity, and Respiration.
• Body Weight and Head Circumference: the study staff will see how much the child weighs and will measure around the child’s head.
• Study Drug: the study staff/doctor will give to the child a dose of IBP-9414 or placebo once per day until he or she reaches a post-menstrual age of 34 weeks and 6 days.
• Other Monitoring: The study staff/doctors will keep a record of the child’s dietary intake, symptoms, medications, and overall clinical condition. This is part of the child’s standard (regular) care.
• The study doctor will record and report any worsening or change of the child’s condition, including the outcome of any surgery or X-ray examinations.
The study doctor or a member of the study staff can answer any questions parents may have about the tests and procedures that are not part of the child’s regular medical care. The only way the child can receive IBP 9414 is within this research study.
After the study is over, parents should talk to the study doctor about future treatment for your child.
If identifiers are removed from the child’s identifiable private information or identifiable samples that are collected during this research, that information or those samples could be used for future research studies or distributed to another investigator for future research studies without your additional informed consent.