| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Mild, moderate and severe atopic dermatitis |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10003639 |
| E.1.2 | Term | Atopic dermatitis |
| E.1.2 | System Organ Class | 100000004858 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The primary comparison of interest is the odds ratio for achievement of of an EASI-50 response at W16. The primary trial objective is to show superiority of EDP1815 over placebo. Primary comparison will be made using a treatment policy strategy with respect to study medication but without regard to treatment compliance or any changes in background therapy. A composite strategy will be used with respect to use of topical corticosteroid rescue therapy with any participants who use these less than 28 days prior to the Week 16 assessment being considered as non- responders. A composite strategy will also be used for participants who withdraw from the study prior to the W16 visit for reasons relating to study medication also being considered as non-responders. A 'while on treatment' strategy will be used for participants who withdraw from the study prior to W16 for reasons considered unrelated to study medication, with the achievement of response at W16 being considered missing. |
|
| E.2.2 | Secondary objectives of the trial |
1. To evaluate the clinical benefit of EDP1815 in the treatment of atopic dermatitis.
2. To evaluate the safety and tolerability of EDP1815.
These objectives will be evaluated using a treatment policy approach with respect to study medication and a composite approach with respect to use of topical corticosteroid rescue therapy within 4 weeks. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Must have given written informed consent (signed and dated) and any authorizations required by local law and be able to comply with all study requirements.
2. Males or females aged ≥ 18 and ≤ 75 years old at the time of informed consent.
3. A diagnosis of atopic dermatitis (AD) meeting Hanifin and Rajka criteria for AD at screening with patient- or clinician- reported disease duration of at least 6 months.
4. Have severity of atopic dermatitis meeting the below criteria at both Screening and Day 1:
i. An IGA of 2, 3 or 4 on the vIGA scale, and;
ii. A BSA of ≥5%, and;
iii. An EASI score of ≥6.
A cap will be set for each of the three IGA severity grades. When this cap is reached, Sponsor will notify sites that participants with severity score at Screening and/or Day 1 matching the closed stratum should be considered ineligible according to Inclusion Criterion 4i.
5. All participants must agree to use a bland additive-free, sodium lauryl sulfate (SLS)-free, and fragrance-free emollient cream, gel or ointment twice daily (or more, as needed) for at least 14 consecutive days immediately prior to randomization and must continue this treatment twice daily throughout the trial.
6. Meet the following contraception criteria:
i. Male participants:
i. 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.
ii. Female participants:
i. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies:
1. Not a WOCBP or
2. A WOCBP who agrees to follow the contraceptive guidance of the protocol during their participation in this study, 28 days prior to the first dose and for at least 1 complete menstrual cycle (≥30 days) after the last dose.
7. Agrees to not increase their usual sun exposure significantly during the study. |
|
| E.4 | Principal exclusion criteria |
1. Atopic dermatitis limited to the hands and/or feet and/or scalp.
2. Have been in a clinical trial for EDP1815 prior to signing of ICF.
3. History of active skin infection within 14 days prior to randomization.
4. Evidence of dermatologic conditions that may, in the opinion of the investigator, interfere with AD evaluation or the assessment of treatment response.
5. Use of phototherapy or tanning beds; systemic medications/treatments that could affect AD or its symptoms including immunosuppressive therapy (e.g., oral or injectable corticosteroids, methotrexate, azathioprine, cyclosporine, mycophenolate mofetil, JAK inhibitors, tacrolimus, and/or leukotriene inhibitor) within 4 weeks of randomization.
6. Previously received any biologic agent for AD and either was:
a. Unresponsive to biologic agent, or
b. Responsive to biologic agent and received this therapy within 3 months or 5 half-lives prior to randomization, whichever is longer.
7. Treatment with topical agents that could affect atopic dermatitis, including topical corticosteroids, topical calcineurin inhibitors (e.g., tacrolimus or pimecrolimus), or topical PDE-4 inhibitor (e.g., crisaborole) within 14 days prior to randomization.
8. Received any investigational or licensed biologic agent for conditions other than AD:
a. Any cell-depleting agent, including rituximab, within 6 months prior to randomization, or until lymphocyte cell counts return to normal, whichever is longer.
b. Any other biologic agent, within 3 months or 5 half-lives prior to randomization, whichever is longer.
9. Gastrointestinal tract disease (e.g., short-bowel syndrome, diarrhea-predominant irritable bowel syndrome) that could interfere with GI delivery and transit time.
10. Active inflammatory bowel disease.
11. Ongoing acute or chronic infectious disease. Patients with hepatitis B, hepatitis C, and HIV may be enrolled provided that the disease is adequately controlled and/or is in remission.
12. Has received live or live-attenuated vaccination within 6 weeks prior to Screening or intends to have such a vaccination during the study. Non-live and non-replicating vaccines are permitted.
13. Clinically significant abnormalities in screening laboratory values that in the opinion of the Investigator would make a participant unsuitable for inclusion in the study. One retest is permitted within the 28-day screening window.
14. Screening Labs: For women, serum creatinine ≥125 μmol/L (1.414 mg/dL); for men, serum creatinine ≥135 μmol/L (1.527 mg/dL).
15. Screening Labs: ALT or AST >2 × ULN.
16. History of clinically significant acute cardiac or cerebrovascular event within 6 months of signing ICF (includes stroke, transient ischemic attack, and coronary heart disease [angina pectoris, myocardial infarction, heart failure, revascularization procedures]).
17. History of active substance (drug and/or alcohol) abuse within the prior 12 months. This does not include the current or prior use of cannabis.
18. In the opinion of the Investigator, evidence of clinically important cardiac conduction abnormalities as judged by the screening ECG.
19. Hypersensitivity to P histicola or to any of the excipients.
20. Active mental or psychiatric disorder, which, in the opinion of the
Investigator or Sponsor, would make the participant unsuitable for
inclusion or could interfere with the participant participating in or
completing the study.
21. Recent major surgery within 3 months of signing the ICF, or major surgery planned during the study.
22. Malignancy within 5 years of signing the ICF, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated.
23. Treatment with another investigational drug or device within 3
months or 5 half-lives of investigational agent prior to randomization,
whichever is longer.
24. Treatment with supplements containing high doses of probiotics and prebiotics as usually found in capsules/tablets/powders, within 14 days prior to randomization and throughout the study period. Note that probiotic and prebiotic foods that contain low doses are allowed (e.g., yoghurt, kefir, kombucha).
25. Unwillingness to comply with study procedures, including follow-up, as specified by this protocol, or unwillingness to cooperate fully with the Investigator.
26. Have any serious conditions that would be anticipated to require the use of systemic corticosteroids or otherwise interfere with study participation or require active frequent monitoring (e.g., unstable chronic asthma).
27. Have any other conditions, which, in the opinion of the Investigator or Sponsor, would make the participant unsuitable for inclusion or could interfere with the participant participating in or completing the study. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy endpoint of the study is the achievement of EASI-50 response at Week 16 |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| The primary endpoints will be evaluated at Week 16 |
|
| E.5.2 | Secondary end point(s) |
• Mean absolute change and percentage change from baseline in EASI Score
• Percentage of Participants Achieving EASI-50 [Time Frame: Week 4, 8 and 12]
• Percentage of Participants Achieving EASI-75
• Percentage of Participants Achieving EASI-90
• Percentage of Participants Achieving Investigator's Global Assessment (vIGA) of 0 or 1 with a ≥2 Point Improvement from baseline
• Percentage of Participants Achieving vIGA of 0 or 1
• Percentage of Participants Achieving vIGA of 0 [Time Frame: Week 16]
• Mean absolute change and percentage change from baseline in vIGA*BSA
• Mean absolute change and percentage change from baseline in BSA
• Percentage of Participants Achieving BSA-50
• Percentage of Participants Achieving BSA-75
• Percentage of Participants Achieving BSA reduction to 3% BSA or less
• Mean absolute change and percentage change from baseline in SCORing Atopic Dermatitis (SCORAD)
• Percentage of Participants Achieving SCORAD-50
• Percentage of Participants Achieving SCORAD-75
• Mean absolute change and percentage change from baseline in DLQI
• Percentage of Participants achieving a reduction of ≥4 in the DLQI, of those with a score of ≥4 at baseline [Time Frame: Week 16]
• Mean absolute change from baseline in worst Pruritus-NRS
• Percentage of Participants achieving a reduction of ≥2 in the worst Pruritus-NRS, of those with a score of ≥2 at baseline
• Percentage of Participants achieving a reduction of ≥4 in the worst Pruritus-NRS, of those with a score of ≥4 at baseline [Time Frame: Week 16]
• Mean absolute change from baseline in SD-NRS score
• Percentage of Participants achieving a reduction of ≥2 in SD-NRS score, of those with a score of ≥2 at baseline [Time Frame: Week 16]
Mean absolute change and percentage change from baseline in Patient Oriented Eczema Measure (POEM)
• Percentage of Participants achieving a reduction of ≥4 in the POEM score, of those with a score of ≥4 at baseline [Time Frame: Week 16]
• Number of courses of rescue therapy per Participant
• Number of days of treatment with rescue therapy per Participant
• Proportion of participants not requiring rescue therapy
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| The secondary endpoints will be evaluated at Weeks 4, 8, 12 and 16 to evaluate the maximum clinical benefit of EDP1815 in the treatment of atopic dermatitis. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 20 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Australia |
| Canada |
| United States |
| Poland |
| Bulgaria |
| Germany |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 1 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 1 |
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