Primary• To evaluate the effect of EDP1815 (same dose using EC1 and EC2 capsules) and EDP2939 (two dose levels using EC2 capsules) on the immune system.Secondary• To evaluate the effect of EDP1815 (same dose using EC1 and EC2 capsules) and EDP2939 (…
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
• KLH-induced immune reaction, after intradermal re-challenge, measured as
basal flow (LSCI) at 24 hours (h).
Secondary outcome
• KLH-induced immune reaction, after intradermal re-challenge, measured as
basal flow (LSCI) at 4h, 48h and 72h.
• KLH-induced immune reaction, after intradermal re-challenge, measured as
flare (LSCI) at 4h, 24h, 48h and 72h.
• KLH-induced immune reaction, after intradermal re-challenge, measured as
erythema (multispectral imaging) at 4h, 24h, 48h and 72h.
• Specific B-cell response to KLH, measured as anti-KLH IgM and IgG
• IMQ-induced immune reaction, measured as basal flow (LSCI) at 24h, 48h and
72h.
• IMQ-induced immune reaction, measured as flare (LSCI) at 24h, 48h and 72h.
• IMQ-induced immune reaction, measured as erythema (multispectral imaging) at
24h, 48h and 72h.
• Serious adverse event (SAE) and adverse event (AE) incidents
• Clinical safety laboratory measurements
• Electrocardiogram (ECG) measurements
• Vital sign measurements
• Physical examination
• Gut microbiota composition in stool samples
- 16S RNA sequencing
Background summary
Keyhole Limpet Hemocyanin (KLH) and imiquimod (IMQ) challenges in healthy
volunteers represent promising methodologies for the evaluation of novel,
immunomodulatory therapeutics.
EDP1815 and EDP2939 are novel therapeutic agents that aim to modulate systemic
inflammation by targeting the small intestinal immunological axis (SINTAXTM)
without systemic drug exposure.
This study, EDP1815-105, will evaluate the pharmacodynamic effects on KLH and
IMQ challenge of EDP1815 in enteric coated capsules utilizing two coating
levels, enteric coating level 1 (EC1 - approximately 58 mg dry weight enteric
coat, original release); as used in study EDP1815-102) and a thinner enteric
coating level 2 (EC2 - approximately 14 mg dry weight enteric coat, earlier
release). Subsequently, the pharmacodynamic effects on the KLH and IMQ
challenge of EDP2939 at two dose levels in capsules with EC2 will be evaluated.
Study objective
Primary
• To evaluate the effect of EDP1815 (same dose using EC1 and EC2 capsules) and
EDP2939 (two dose levels using EC2 capsules) on the immune system.
Secondary
• To evaluate the effect of EDP1815 (same dose using EC1 and EC2 capsules) and
EDP2939 (two dose levels using EC2 capsules) on the immune system.
• To evaluate the safety and tolerability of EDP1815 in two enteric coated
capsule dosage forms.
• To evaluate the safety and tolerability of EDP2939 at different doses
Study design
This is a single-center, randomized, double-blind, placebo-controlled, platform
trial to evaluate the effects of EDP1815 and EDP2939 on the systemic immune
system, using KLH and IMQ challenges.
Intervention
Cohort 1: EDP1815, 1 capsule QD, 8x10^10 cells per capsule (EC1)
Cohort 2: EDP1815, 1 capsule QD, 8x10^10 cells per capsule (EC2)
Cohort 3: EDP2939, 1 capsule QD, 3.9x10^12 EV per capsule (EC2).
Cohort 4: EDP2939, 1 capsule QD, up to 7.5x1013 EV per capsule (EC2). Dose will
be confirmed based on interim safety review of multiple dose escalation part of
EDP2939-101
All subjects will undergo 3 KLH intramuscular administrations, 1 intradermal
KLH administration, and 3 consecutive days of topical IMQ administration.
Study burden and risks
The study will be conducted in healthy volunteers. Both the KLH challenge and
IMQ challenge have been conducted in healthy volunteers before.
Participants in this study are healthy volunteers and are not expected to
experience therapeutic benefit from exposure to EDP1815 or EDP2939.
EDP1815 is a pharmaceutical preparation of a single strain of P. histicola, a
commensal found in all human populations studied to date. EDP1815
drug-substance has viability of <0.02% and is not genetically modified. While
P. histicola is a human commensal, it is a potentially pathogenic
micro-organism. Most frequently reported are urinary tract infections with a
relatively mild clinical course, in most cases in immune-compromised patients,
who are not part of the current protocol. P. histicola and EDP1815 specifically
have been tested and found to be sensitive for various antibiotics, which will
be administered in the current protocol if necessary.
Across the Phase 1 and 2 studies to date, EDP1815 has demonstrated a safety
profile similar to placebo at doses up to 1.28 x1012 cells per day for
durations up to 8 weeks (cohort 8 of study EDP1815-101), and up to 8x1011 cells
per day for 16 weeks (e.g. in psoriasis phase 2 study EDP1815-201). There have
been no drug-related serious adverse events, no SUSARs and no adverse events of
severe intensity. No subjects required cessation of dosing due to a
drug-related AE.
EDP2939 comprises EVs from EDP1815, and thereby is non-viable and does not
include the parent microbe. EDP1815 contains both the parent microbe and EVs
(EDP2939) hence the risk profile of EDP2939 is expected to be similar to
EDP1815. Doses of EDP2939 to be used in the current study will be qualified by
prior Phase 1 safety data from EDP2939-101.
The study design and challenge methodology to be used in the current study has
been used previously in many other CHDR studies, and is accepted by scientists
and regulatory authorities.
For a structured risk assessment see Section 10.
Memorial Drive 620
Cambridge MA 02139
US
Memorial Drive 620
Cambridge MA 02139
US
Listed location countries
Age
Inclusion criteria
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 45 years, inclusive.
3. Participant has a body mass index of >= 18 kg/m2 to <= 35 kg/m2 at Screening.
6. The participant has clinical laboratory evaluations (including clinical
chemistry, haematology, and complete urine analysis) 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, vital signs, physical examination, laboratory tests
and ECGs at Screening and on Day -1.
Exclusion criteria
9. The participant has used Aldara® (imiquimod cream) within 3 weeks prior to
the baseline visit or plans to use it during the course of the study.
10. Previous known exposure to Immucothel® or KLH.
12. The participant has a history of hypersensitivity or allergies to
Prevotella (or Prevotella containing probiotics) including any associated
excipients for EDP1815 or EDP2939, or has a history of hypersensitivity or
allergies to placebo capsule/powder (magnesium stearate, microcrystalline
cellulose, colloidal silicon dioxide, hydroxypropylmethylcellulose, or
mannitol) or to the hard capsule shells (hydroxylpropylmethylcellulose and
titanium dioxide), or has a known allergy against Alhydrogel®, or has a known
allergy against Aldara® (imiquimod cream).
16. The participant has any current and / or recurrent pathologically,
clinically significant skin condition at the treatment area (i.e., atopic
dermatitis), including tattoos. Treatment area includes the forearms and back.
19. History of pathological scar formation (keloid, hypertrophic scar) or
keloids or surgical scars in the target treatment area that in the opinion of
the investigator, would limit or interfere with dosing and/or measurement in
the trial.
20. Diagnosed with psoriasis.
21. History of skin cancer (basal cell carcinoma, squamous cell carcinoma,
melanoma).
22. Tanning due to sunbathing, excessive sun exposure or a tanning booth within
3 weeks before start of treatment (Day 1) and for the duration of the study.
23. History of Schistosomiasis (infection with Schistosoma parasite).
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR202200097537-NL |
| CCMO | NL81037.056.22 |