A study to test the effect of experimental drugs EDP1815 and EDP2939 on skin inflammation in healthy volunteers after KLH and imiquimod challenge
| ISRCTN | ISRCTN29254828 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN29254828 |
| EudraCT/CTIS number | 2022‐000975‐37 |
| ClinicalTrials.gov number | NCT05682222 |
| Secondary identifying numbers | CHDR2158 |
- Submission date
- 20/06/2022
- Registration date
- 01/07/2022
- Last edited
- 24/05/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Skin and Connective Tissue Diseases
Plain English Summary
Background and study aims
EDP1815 and EDP2939 possibly have a regulating effect on the immune reaction. Therefore, they may be used in the treatment of diseases involving an overactive immune reaction, such as the skin diseases eczema and psoriasis. In this study, the effect of EDP1815 and EDP2939 on the immune reaction will be measured. Two different immune reactions will be induced, one by injections (KLH reaction) and one with a cream on the skin (imiquimod reaction).
Who can participate?
Healthy volunteers aged 18 to 45 years (inclusive)
What does the study involve?
Participants will take EDP1815 or EDP2939 every day for 2 months. They will receive KLH injections on 3 different days. After 2 months, the KLH reaction will be induced on the skin with an injection in the skin. The reaction will be measured by different cameras. For 3 consecutive days, the imiquimod cream will be applied to the skin. This reaction will also be measured by different cameras. Inflammation of the skin after imiquimod application will also be measured in blister fluid. To this purpose, four blisters will be made on the skin where imiquimod was applied.
What are the possible benefits and risks of participating?
There are no benefits of participating. Participants possibly contribute to a new treatment of auto-immune diseases. EDP1815 and EDP2939 have already been administered to people and there have been no side effects of concern. However, these are investigational drugs so there may be side effects we don't yet know about and that could happen. KLH injection can cause redness, itching and swelling of the skin at the site of injection, but these effects normally don't last more than 3-4 days. Imiquimod challenge can cause redness, itching, pain, tingling and skin peeling where the imiquimod has been applied. Blisters can cause discoloration of the skin, which usually disappears after a few weeks. However, in rare cases the discoloration can stay present for months to years.
Where is the study run from?
Centre of Human Drug Research (Netherlands)
When is the study starting and how long is it expected to run for?
June 2022 to May 2023
Who is funding the study?
Evelo Biosciences (USA)
Who is the main contact?
B. Eveleens Maarse, beveleensmaarse@chdr.nl
Contact information
Public
Zernikedreef 8
Leiden
2333 CL
Netherlands
 ORCID ID |
0000-0003-1763-3122 |
|---|---|
| Phone | +31 (0)71 5246 400 |
| beveleensmaarse@chdr.nl |
Study information
| Study design | Single-center randomized double-blind placebo-controlled multiple-dose platform trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Other |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a participant information sheet. |
| Scientific title | A Phase I, randomized, double-blind, placebo-controlled, multiple-dose platform study investigating the immunopharmacology of EDP1815 and EDP2939 |
| Study hypothesis | Both EDP1815 and EDP2939 exert an immunomodulatory effect which will significantly attenuate the dermal immune reactions to KLH and imiquimod challenge. |
| Ethics approval(s) | Approved 20/05/2022, Stichting Stichting Beoordeling Ethiek Biomedisch Onderzoek (BEBO) (Doctor Nassaulaan 10, 9401 HK Assen, The Netherlands; +31 (0)592 405871; info@stbebo.nl), ref: NL81037.056.22 |
| Condition | KLH and imiquimod induced skin inflammation in healthy volunteers |
| Intervention | The active drug will be EDP1815 in Cohorts 1 and 2, and EDP2939 in Cohorts 3 and 4. In all cohorts, subjects will be randomized 2:1 to receive active or placebo treatment. The study drug will be administered daily from Day 1 up until Day 60 through oral self-administration; on clinic visit days, the study drug will be administered at the clinic. An unblinded statistician generates a randomization list (active:placebo = 2:1). Study drug will be dispensed by an unblinded pharmacist. The randomization list will be made available to the pharmacist preparing the study drug, and to statisticians or programmers involved in preparing blinded summaries, graphs and listings. All other study staff and participants will be blinded until the database is locked. Cohorts 1 and 2 will take one capsule EDP1815 per day (dose_ 8 x10¹² cells) for a duration of 60 days. Cohort 1 will receive capsules with normal enteric coating, cohort 2 will receive capsules with an early release coating. Cohorts 3 and 4 will take one capsule EDP2939 per day (dose cohort 3_ 3.9 x10¹² eTPN, dose cohort 4 maximal 7.5 x10¹³ eTPN, both with early release coatings) for a duration of 60 days. Subjects will be present on Day -1 for initial baseline procedures, and again on Day 1 for remaining baseline procedures and initial dosing of study drug, and to receive instructions on study drug storage and dosing at home. Subjects will present to the Centre for Human Drug Research (CHDR) on days 8, 22, and 36 to receive intramuscular KLH immunisations. Subjects will present on Day 57 to receive intradermal KLH administration and to start topical administration of Imiquimod. All study visits will consist of ambulatory visits. Imiquimod will also be administered on days 58 and 59. The follow-up visit will be 12 to 16 days after the last dose of the study drug. KLH-challenge: KLH will be administered by intramuscular injection. The KLH challenge will be performed by intradermal administration. Imiquimod-challenge: imiquimod will be administered topically. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | EDP1815, EDP2939 |
| Primary outcome measure | KLH-induced immune reaction after intradermal re-challenge, measured as basal flow (laser speckle contrast imaging [LSCI]) at 24 h |
| Secondary outcome measures | 1. KLH-induced immune reaction after intradermal re-challenge, measured as basal flow (LSCI) at 4 h, 48 h and 72 h 2. KLH-induced immune reaction after intradermal re-challenge, measured as flare (LSCI) at 4 h, 24 h, 48 h and 72 h 3. KLH-induced immune reaction after intradermal re-challenge, measured as erythema (multispectral imaging) at 4 h, 24 h, 48 h and 72 h 4. Specific B-cell response to KLH, measured as anti-KLH IgM and IgG at 1, 22, 36 and 57 days 5. IMQ-induced immune reaction, measured as basal flow (LSCI) at 24 h, 48 h and 72 h 6. IMQ-induced immune reaction, measured as flare (LSCI) at 24 h, 48 h and 72 h 7. IMQ-induced immune reaction, measured as erythema (multispectral imaging) at 24 h, 48 h and 72 h |
| Overall study start date | 08/02/2022 |
| Overall study end date | 23/05/2023 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 45 Years |
| Sex | Both |
| Target number of participants | 72 |
| Total final enrolment | 38 |
| Participant inclusion criteria | 1. Capable of giving signed informed consent, and willing to comply with requirements of the study 2. Age 18 years to 45 years, inclusive 3. Body mass index of 18 to 35 kg/m2, inclusive 4. Caucasian 5. Healthy based on medical history, physical examination, blood pressure, ECG and blood and urine laboratory tests |
| Participant exclusion criteria | 1. Use of Aldara® (imiquimod cream) within 3 weeks prior to the study 2. Has previously received Immucothel® or KLH 3. Allergy to Alhydrogel® or Aldara® (imiquimod cream) 4. Current or recurrent skin diseases affecting the arms or back, or extensive tattoos in these areas 5. Previous diagnosis of psoriasis 6. History of pathological scar formation (e.g. keloid scar) 7. History of skin cancer (basal cell carcinoma, squamous cell carcinoma, melanoma) 8. Significant bowel disease (e.g. inflammatory bowel disease, coeliac disease) 9. Currently has an infection or has needed antibiotics within 6 weeks before the study 10. Current smoker of more than 5 cigarettes per day 11. Tanning due to sunbathing, excessive sun exposure or a tanning booth within 3 weeks before the start of the study 12. History of schistosomiasis (infection with Schistosoma parasite) |
| Recruitment start date | 20/05/2022 |
| Recruitment end date | 01/07/2023 |
Locations
Countries of recruitment
- Netherlands
Study participating centre
Leiden
2333 CL
Netherlands
Sponsor information
Industry
620 Memorial Drive
Cambridge
MA 02139
United States of America
| Phone | +44 (0)7397 082840 |
|---|---|
| clinicaltrials@evelobio.com | |
| Website | https://evelobio.com/ |
Funders
Funder type
Industry
No information available
Results and Publications
| Intention to publish date | 01/11/2023 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | Planned publication in a high-impact-peer-reviewed journal |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are not expected to be made available due to proprietary reasons. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | 15/05/2024 | 24/05/2024 | Yes | No |
Editorial Notes
24/05/2024: The following changes were made:
1. Publication reference added.
2. ClinicalTrials.gov number added.
11/09/2023: The following changes were made to the trial record:
1. The overall end date was changed from 30/09/2023 to 23/05/2023.
2. The total final enrolment was added.
03/05/2023: IPD sharing statement added.
20/02/2023: The following changes were made to the trial records:
1. The recruitment end date was changed from 22/02/2023 to 01/07/2023.
2. The overall trial end date was changed from 04/05/2023 to 30/09/2023.
3. The intention to publish date was changed from 18/11/2023 to 01/11/2023.
27/06/2022: Trial’s existence confirmed by Stichting Beoordeling Ethiek Biomedisch Onderzoek.
