E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 |
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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 |
To explore the efficacy and safety of KY1005 on the signs of atopic dermatitis (AD) using the Eczema Area and Severity Index (EASI) and the incidence of treatment-emergent adverse events (TEAEs). |
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E.2.2 | Secondary objectives of the trial |
To explore/characterise: To explore the effect of KY1005 on change in EASI over time - The effect of KY1005 on additional physician assessments of AD activity/severity (EASI, EASI 50, EASI 75, EASI 90, validated Investigator Global Assessment [vIGA], SCORing of Atopic Dermatitis [SCORAD] Index and affected body surface area [BSA]). - The effect of KY1005 on patient-reported AD activity/severity (Patient Oriented [PO] Eczema Measure [POEM], PO-SCORAD Index, Dermatology Quality of Life Index [DLQI] and Numerical Rating Scale [NRS] for pruritus). - The pharmacodynamic (PD) response to KY1005 including: ¤ change in histopathology; ¤ change in immunohistochemistry; ¤ the anti-KY1005 antibody response. - The pharmacokinetics (PK) of KY1005. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Adults (≥ 18 years but < 75 years of age) with AD for 1 year or longer at Baseline (Day 1; prior to first administration of IMP). - EASI of 12 or higher at the Screening Visit and 16 or higher at Baseline. - vIGA of 3 or 4 at Baseline. - AD involvement of 10% or more of body surface area (BSA) at Baseline. - Documented history, within 6 months prior to Baseline, of either inadequate response to topical treatments or inadvisability of topical treatments. - Must have applied a stable dose of topical bland emollient (simple moisturiser, no additives [e.g., urea]) at least twice daily for at least 7 consecutive days before Baseline. - Able and willing to comply with requested study visits/telephone visits and procedures. - Able and willing to provide punch biopsy of both lesional and non-lesional skin at Baseline. - Able and willing to provide written informed consent. |
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E.4 | Principal exclusion criteria |
- Treatment with any of the following prior to first IMP administration (Baseline): ¤ Systemic corticosteroids and tacrolimus within 4 weeks; ¤ Systemic cyclosporin A within 3 weeks; ¤ Other systemic immunosuppressive or immunomodulatory drugs (including leukotriene inhibitors) within 3 months; ¤ Topical corticosteroids, tacrolimus or pimecrolimus, within 2 weeks; ¤ Prescription or non-prescription moisturisers with additives (e.g., urea, filaggrin) within 2 weeks; ¤ Phototherapy or allergen immunotherapy within 4 weeks; ¤ Regular use (> 2 visits/week) of a tanning booth/parlour within 4 weeks; ¤ Dupilumab within 3 months; ¤ Investigational therapy for the treatment of other conditions within 5 half-lives or the limit of PD effects or 3 months where the t1/2 is not known. - Known history of or suspected significant current immunosuppression, including history of invasive opportunistic infections despite infection resolution or otherwise recurrent infections of abnormal frequency or prolonged duration. - Treatment with a live (attenuated) immunisation within 12 weeks prior to Baseline. - Men and women (of reproductive potential) unwilling to use birth control and women who are pregnant or breast feeding. - Basal and squamous cell skin cancer in the last 3 years prior to Baseline. Any other malignancies in the last 5 years prior to Baseline (excluding in situ cervical carcinoma). - Positive for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb) or hepatitis C antibody at the Screening Visit. - Severe concomitant illness that would in the Investigator’s opinion inhibit the patient’s participation in the study, including for example, but not limited to, renal disease, neurological conditions, heart failure and pulmonary disease. - Laboratory values at the Screening Visit: ¤ Serum creatinine > 1.6 mg/dL (141 μmol/L) in female patients and > 1.9 mg/dL (168 μmol/L) in male patients; ¤ Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 1.5 × upper limit of normal (ULN); ¤ Platelet count < 100 × 109/L; ¤ Haemoglobin (Hb): Male < 13.5g/dL and Female <12g/dL; ¤ White blood cell count (WBCC) < 3.0 × 109/L; ¤ Absolute neutrophil count < 2.0 × 109/L; ¤ Absolute lymphocyte count < 0.5 × 109/L; ¤ Total bilirubin > ULN (except in circumstances where Gilbert`s Syndrome can be confirmed) - Participation in any other clinical study, including non-interventional studies. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Co-primary endpoints: - Percentage change in EASI from Baseline to Day 113. - Incidence of TEAEs. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
- Percentage change in EASI: from Baseline to Day 113 - Incidence of TEAEs to Day 113 |
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E.5.2 | Secondary end point(s) |
Main secondary endpoints:
Efficacy endpoint: - Percentage and absolute change from Baseline in EASI over time.
PD and histopathology endpoints: - Change in epidermal thickness from Baseline to Day 113. - Change in immunohistochemistry staining from Baseline to Day 113.
Additional secondary endpoints:
Efficacy endpoints: - Percentage of patients with at least a 50% reduction from Baseline in EASI (EASI 50) to Day 113. - Percentage of patients with at least a 75% reduction from Baseline in EASI (EASI 75) to Day 113. - Percentage of patients with at least a 90% reduction from Baseline in EASI (EASI 90) to Day 113. - Change in vIGA from Baseline to Day 113 and over time. - Percentage of patients with a response of vIGA 0 or 1 at Day 113 and over time. - Change in SCORAD Index from Baseline to Day 113 and over time. - Change in affected BSA from Baseline to Day 113 and over time. - Change in POEM from Baseline to Day 113 and over time. - Change in PO-SCORAD Index from Baseline to Day 113 and over time. - Change in DLQI from Baseline to Day 113 and over time. - Change in NRS for pruritus from Baseline to Day 113 and over time.
PD endpoints: - Immunogenicity titres at various timepoints from Baseline to Day 113.
Pharmacokinetic endpoints for each patient (receiving KY1005) including: - Cmax - tmax - Cmin - AUC |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Various timepoints for all endpoints assessment will be from Baseline to Day 113 and over time where indicated. |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Proteinomic, transcriptomic and histopathological assessment |
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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 | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
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 | 3 |
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 | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
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 | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
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
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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 | 7 |
E.8.9.1 | In the Member State concerned days | 7 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 7 |