A phase 1, double-blind, randomised, placebo-controlled multiple dose study investigating the immunopharmacology of EDP1815 with multiple formulations
- Conditions
- 10027665Auto immune diseases
- Registration Number
- NL-OMON49769
- Lead Sponsor
- Evelo Biosciences Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 48
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, does
not plan to become 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 3 complete menstrual cycles (*90
days) after last EDP1815 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. 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. Fitzpatrick skin type I-III (Caucasian).
8. 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.
9. Subject needs to have sufficient space in a refrigerator to store the IMP
during the ambulant dosing phase.
10. Participant has the ability to communicate well with the Investigator in
the Dutch language and willing to comply with the study restrictions.
Only subjects with a negative SARS-CoV-2 qPCR analysis prior to first dosing
will be included in the study
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 EDP1815 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. 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, microcrystalline cellulose, colloidal
silicon dioxide, hydroxypropylmethylcell
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>* KLH challenge<br /><br>o DTH after intradermal KLH re-challenge. Response characterization by Laser<br /><br>Speckle Contrast Imaging (LSCI) and erythema by multispectral imaging<br /><br>o Serology: anti-KLH IgM and IgG<br /><br>o Ex vivo lymphocyte activation upon KLH re-challenge. Response<br /><br>characterization by ELISPOT.<br /><br>o Suction blister exudates: cytokines TNF*, IL8, IFN-*, IL6, IL-1*, IL-10,<br /><br>IL-33, TSLP, and immunophenotyping from cohort 2 onwards<br /><br>* Whole blood ex-vivo Phytohaemagglutinin (PHA) and Lipopolysaccharide (LPS)<br /><br>challenges with cytokine release (LPS: TNF*, IL-6, IL-1b, IL-8, IL-2, IFN-*<br /><br>and IL-10. PHA: IL-2 en IFN-*) as read-out measured by MSD.<br /><br>* (Changes in) regulatory T cells and B cell subsets<br /><br>* Blood chemokine and cytokine levels</p><br>
- Secondary Outcome Measures
Name Time Method <p>* Serious adverse event (SAE) and adverse event (AE) incidents<br /><br>* Clinical safety laboratory measurements<br /><br>* Electrocardiogram (ECG) measurements<br /><br>* Vital sign measurements<br /><br>* Chemistry and hematology panels<br /><br>* Physical examination<br /><br>* Bristol Stool Scale and stool questionnaire<br /><br>* Persistent EDP1815 prevalence in stool samples<br /><br>o Strain-specific PCR<br /><br>* Gut microbiota composition in stool samples<br /><br>o 16S RNA sequencing<br /><br>* Specific markers of gastrointestinal (GI) integrity<br /><br>o Faecal calprotectin (only cohort 1)<br /><br>* Immune biomarkers<br /><br>o Cytokines e.g. TNF-* and IL-6<br /><br>o Immunoglobulins e.g. IgG (including individual subclasses IgG1 to IgG4), IgM,<br /><br>IgA<br /><br>* Leukocyte subsets e.g. CD3+, CD4+, CD8+, CD19+, NK-cells and CD14+</p><br>