Auto immune diseases
Conditions
Interventions
EDP1066
KLH
Sponsors
Evelo Biosciences Inc.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Participants are eligible to be included in the study only if all of the following criteria apply: 1. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Obtained prior to any screening procedures and in accordance with national, local, institutional guidelines. 2. Age * 18 years to 60 years, inclusive. 3. Participant has a body mass index of * 18 kg/m2 to * 35 kg/m2 at Screening. 4. Contraception: a. Male participants: * A male participant must agree to use contraception as indicated in Section 4.5.1 during their participation in this study and for a period of 90 days after the last dose and refrain from donating sperm during this period. b. Female participants: * A female participant is eligible to participate if she is not pregnant, does not plan to become pregnant during the study, not breastfeeding, and at least 1 of the following conditions applies: i. Not a woman of child-bearing potential (WOCBP) OR ii. A WOCBP who agrees to follow the contraceptive guidance during their participation in this study as indicated in Section 4.5.1 and for at least 3 complete menstrual cycles (*90 days) after last EDP1066 dose. 5. CRP * 10 mg/L and faecal calprotectin * 150 mcg/g faeces. Exceedings of these thresholds may be allowed by the investigator if deemed clinically irrelevant. 6. Participant has clinical laboratory evaluations (including clinical chemistry, haematology, and complete urinalysis) within the reference range for the testing laboratory, unless the results are deemed not to be clinically significant by the investigator (1 repeat test is permitted). 7. Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring at Screening and on Day 1. 8. Participant has the ability to communicate well with the Investigator in the Dutch language and willing to comply with the study restrictions. 9. Subject needs to have sufficient space in a refrigerator to store the IMP during the ambulant dosing phase.
Exclusion criteria
Exclusion criteria: 1. Participant has received live attenuated vaccination within 42 days prior to Screening or intends to have vaccinations during the course of the study. 2. Participant has received any investigational drug or experimental procedure within 90 days or 5 half-lives, whichever is longer, prior to study intervention administration or participant was enrolled in an investigational drug or device study within 90 days prior to first EDP1066 dosing. 3. Participant requires treatment with an anti-inflammatory drug or prophylactic antibiotics for any reason during the study period. Paracetamol will be permitted for use as an antipyretic and/or analgesic (maximum of 4 grams/day in any 24-hour period). 4. Participant has an active infection (e.g. sepsis, pneumonia, abscess) or recurrent infection, or has had an infection requiring antibiotic treatment within 42 days prior to Investigational Medicinal Product (IMP) administration. 5. Participant is diagnosed with tuberculosis (TB, as per positive skin test (Mantoux) or IFN-* release assay), or history of TB, or latent TB, or recent contact with TB (patient); having travelled to countries where TB is endemic within 56 days of planned drug administration or planning to travel to countries where TB is endemic from the moment of drug administration until 90 days after the end of the study. 6. Participant has renal or liver impairment, defined as: a. For women, serum creatinine level * 125 *mol/L; for men, * 135 *mol/L b. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) * 1.5 x upper limit of normal (ULN), or c. Alkaline phosphatase (ALP) and/or bilirubin > 1.5 x ULN Exceedings of these thresholds may be allowed by the investigator if deemed clinically irrelevant. 7. Participant has active neoplastic disease or history of neoplastic disease within 5 years of Screening (except for basal or squamous cell carcinoma of the skin or carcinoma in situ that has been definitively treated with standard of care). 8. Impaired cardiac function or clinically significant cardiac diseases, including any of the following: a. Unstable angina or acute myocardial infarction * 90 days prior to Screening; b. Clinically significant heart disease (e.g. symptomatic congestive heart failure [e.g. >New York Heart Association [NYHA] Class 2]; uncontrolled arrhythmia, or hypertension; history of labile hypertension or poor compliance with an antihypertensive regimen. 9. Participant with a positive screening result for hepatitis B surface antigen, anti-hepatitis B core, hepatitis C, or HIV. 10. Participants with gastrointestinal tract disease (e.g. short bowel syndrome, diarrhoea predominant irritable bowel syndrome [IBS], celiac disease) that could interfere with the subject*s safety or pharmacodynamic effect of the monoclonal microbial. 11. Serious psychiatric or medical conditions that, in the opinion of the investigator, could interfere with treatment, compliance, or the ability to give consent. 12. Participant has a history of hypersensitivity or allergies to Lactococcus (or Lactococcus containing probiotics) including any associated excipients, or has a history of hypersensitivity or allergies to placebo capsule/powder (magnesium stearate, microcrystalline cellulose, colloidal silicon dioxide, hydroxypropylmethylcellulose, o
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| o KLH challenge * Serum anti-KLH IgM and IgG titres * LSCI * basal flow and flare * multispectral imaging * CIELAB colour level a* and Haemoglobin average level * Ex-vivo lymphocyte activation o Whole blood ex-vivo PHA and LPS challenges with cytokine release as read-out measured by MSD. o Circulating regulatory T cells and B cell subsets | — |
Secondary
| Measure | Time frame |
|---|---|
| o Treatment-emergent (serious) adverse events ((S)AEs). o Clinical laboratory tests * Haematology * Chemistry * Urinalysis o Vital signs * Pulse Rate (bpm) * Systolic blood pressure (mmHg) * Diastolic blood pressure (mmHg) o ECG * Heart Rate (HR) (bpm), PR, QRS, QT, QTcF o Physical examination o Bristol stool scale o Stool questionnaire o Blood immunological markers * Cytokines e.g. TNF-*, IFN-*, IL-1*, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13 * Immunoglobulins e.g. IgG (including individual subclasses IgG1 to IgG4), IgM, IgA * Leukocyte subsets e.g. CD3+, CD4+, CD8+, CD19+, NK-cells and CD14+ o Specific markers of GI integrity * Faecal calprotectin o EDP1066 prevalence in stool samples (transit time and persistence) * Strain-specific PCR o Faecal microbiome composition * 16S RNA sequencing | — |
Countries
Netherlands
Outcome results
None listed