Multiple ascending dose KLH antigen challenge study of EDP1815

Conditions: Auto immune diseases

Registration Number: NL-OMON20845

Lead Sponsor: Evelo Biosciences Inc.

Brief Summary: .A.

Detailed Description: Not available

Recruitment & Eligibility

Status: Pending

Sex: Not specified

Target Recruitment: 48

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 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, 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 and for at least 1 complete menstrual cycle (=30
days) after last dose.
5. CRP = 10 mg/L and faecal calprotectin = 150 mcg/g faeces
6. The 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. Subject needs to have sufficient space in a refrigerator to store the IMP
during the ambulant dosing phase.
9. Participant has the ability to communicate well with the Investigator in
the Dutch language and willing to comply with the study restrictions.

Exclusion Criteria

1. Female participant who is pregnant, or plans to become pregnant
during the study, or breastfeeding, or sexually active with child-bearing
potential who is not using a medically accepted birth control method.
2. Participant has received live attenuated vaccination within 6 weeks
prior to Screening or intends to have vaccinations during the course of the
study.
3. Participant has received any investigational drug or experimental
procedure within 90 days or 5 half-lives, whichever is longer, prior to study
intervention administration.
4. Participant was enrolled in an investigational drug or device study
within 3 months prior to first dosing.
5. Participant requires treatment with an anti-inflammatory drug 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).
6. Participant has an active infection (e.g. sepsis, pneumonia, abscess) or
recurrent infection, or has had an infection requiring antibiotic treatment
within 6 weeks prior to Investigational Medicinal Product (IMP)
administration.
7. 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 eight weeks of planned drug administration or planning to
travel to countries where TB is endemic from the
moment of drug administration until three months after the end of the
study.
8. Patient requires prophylactic antibiotics for any reason
9. Participant has renal or liver impairment, defined as:
a. For women, serum creatinine level = 125 µmol/L; for men, = 135 µmol/L
b. An estimated creatinine clearance (MDRD formula) <60 mL/min
c. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =
1.5 x upper limit of normal (ULN), or
d. Alkaline phosphatase (ALP) and/or bilirubin > 2.5 x ULN
10. 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).
11. Impaired cardiac function or clinically significant cardiac diseases,
including any of the following:
a. Unstable angina or acute myocardial infarction = 3 months 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.
12. Participant with a positive screening result for hepatitis B surface
antigen, anti-hepatitis B core, hepatitis C, or HIV.
13. 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.
14. Serious psychiatric or medical conditions that, in the opinion of the
investigator, could interfere with treatment, compliance, or the ability to
give consent.
15. The participant has a history of hypersensitivity or allergies to
Prevotella (or Prevotella containing probiotics) including any associated
excipients, or has a history of hypersensitivity or allergies to placebo
capsule/powder (magnesium stearate and cellulose) or to the hard
capsule shells (hydroxyl propyl methyl cellu

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
* KLH challenge<br>o Delayed type hypersensitivity after<br>intradermal KLH re-challenge. Response characterization by Laser<br>Speckle Contrast Imaging and erythema by Antera 3D imaging<br>o Serology: anti-KLH IgM and IgG<br>o Ex vivo lymphocyte activation upon KLH re-challenge. Response<br>characterization by ELISPOT.<br>* (Changes in) regulatory T cells<br>* Blood chemokine and cytokine levels

Secondary Outcome Measures

Name	Time	Method
* Serious adverse event (SAE) and adverse<br>event (AE) incidents<br>* Clinical safety laboratory measurements<br>* Electrocardiogram (ECG) measurements<br>* Vital sign measurements<br>* Chemistry and hematology panels<br>* Physical examination<br>* Bristol Stool Scale and stool questionnaire<br>* Persistent EDP1815 prevalence in stool<br><br>Samples<br>* Gut microbiota composition in stool samples<br>* Specific markers of gastrointestinal (GI)<br><br>integrity<br>o Faecal calprotectin<br>* Immune biomarkers<br>o Cytokines e.g. TNF-a, IFN-?, IL-1ß, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13<br>o Immunoglobulins e.g. IgG (including individual subclasses IgG1 to IgG4),<br>IgM, IgA<br>*Leukocyte subsets e.g. CD3+, CD4+, CD8+, CD19+, NK-cells and<br>CD14+