A phase 1, double-blind, randomised, placebo-controlled multiple dose study investigating the immunopharmacology of EDP1066 with multiple formulations
- Conditions
- Auto immune diseases10027665
- Registration Number
- NL-OMON48298
- Lead Sponsor
- Evelo Biosciences Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 80
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.
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>o KLH challenge<br /><br>* Serum anti-KLH IgM and IgG titres<br /><br>* LSCI * basal flow and flare<br /><br>* multispectral imaging * CIELAB colour level a* and Haemoglobin average level<br /><br>* Ex-vivo lymphocyte activation<br /><br>o Whole blood ex-vivo PHA and LPS challenges with cytokine release as read-out<br /><br>measured by MSD.<br /><br>o Circulating regulatory T cells and B cell subsets</p><br>
- Secondary Outcome Measures
Name Time Method <p>o Treatment-emergent (serious) adverse events ((S)AEs).<br /><br>o Clinical laboratory tests<br /><br>* Haematology<br /><br>* Chemistry<br /><br>* Urinalysis<br /><br>o Vital signs<br /><br>* Pulse Rate (bpm)<br /><br>* Systolic blood pressure (mmHg)<br /><br>* Diastolic blood pressure (mmHg)<br /><br>o ECG<br /><br>* Heart Rate (HR) (bpm), PR, QRS, QT, QTcF<br /><br>o Physical examination<br /><br>o Bristol stool scale<br /><br>o Stool questionnaire<br /><br>o Blood immunological markers<br /><br>* Cytokines e.g. TNF-*, IFN-*, IL-1*, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13<br /><br>* 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+<br /><br>o Specific markers of GI integrity<br /><br>* Faecal calprotectin<br /><br>o EDP1066 prevalence in stool samples (transit time and persistence)<br /><br>* Strain-specific PCR<br /><br>o Faecal microbiome composition<br /><br>* 16S RNA sequencing</p><br>