| 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 characterize the efficacy (including dose/exposure-response) across a range of KY1005 exposures, compared to Placebo, on the signs of Atopic Dermatitis (AD) using the Eczema Area and Severity Index (EASI) in those patients with a documented history, within 6 months prior to Baseline, of either inadequate response to topical treatments or inadvisability of topical treatments. Dose response of 4 different dose regimens of KY1005 in patients with AD versus Placebo will be evaluated. |
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| E.2.2 | Secondary objectives of the trial |
To characterize:
*The efficacy (including dose/exposure-response) across a range of
KY1005 exposures compared to Placebo on additional physician
assessments of AD activity/severity: EASI at week24, EASI-75, IGA and NRS for pruritus.
Also characterize:
*Safety and tolerability of KY1005
*The PK profile of KY1005 across a range of doses/exposures
*The response across a range of KY1005 exposures on additional
physician assessments of AD activity/severity EASI, EASI-50, EASI-75,
EASI-90, EASI-100, IGA, SOCRAD and affected BSA.
*The response across range of KY1005 exposures on patient-reported
AD activity/severity; POEM, DLQI, ADCT, HADS & NRS for pruritus.
*The PD response to KY1005 including but not limited to; the
immunogenicity of KY1005, including the anti-KY1005 antibody
response.
*The maintenance of clinical response with in patients randomized to
withdrawal of IMP who achieve ≥ EASI-75 or who attain IGA 0/1
response following 24 weeks of treatment. |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Within existing study protocol KY1005-CT05:
Skin punch biopsies (5 mm) will be taken in up to approximately one third (30%) of patients who will be enrolled into a skin biopsy sub-study. This will be done at selected sites. Lesional and non-lesional samples will be collected at Baseline with lesional samples requested at Day 113. |
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| E.3 | Principal inclusion criteria |
• Adults (18 to < 75 years of age) with AD for 1 year or longer at Baseline (Day 1; prior to first administration of IMP).For United Kingdom, see Section 17.15.2 (Appendix 15).
• EASI of 12 or higher at the Screening Visit and 16 or higher at Baseline.
• IGA of 3 or 4 at Baseline.
• AD involvement of 10% or more of BSA at Baseline.
• Baseline worst/maximum pruritus NRS of ≥ 4. The baseline weekly average of daily worst/maximum pruritus NRS will be calculated from the 7 consecutive days immediately preceding the Baseline visit.
• Documented history, within 6 months prior to Baseline, of either inadequate response or inadvisability of topical treatments.
• Must have applied a stable dose of topical bland emollient (simple moisturizer, no additives [e.g., urea]) at least twice daily for a minimum of 7 consecutive days before Baseline.
• Able to complete patient questionnaires, including collection of NRS (pruritus) on each of the 7 days prior to Baseline. .
• Able and willing to comply with requested study visits/telephone visits and procedures.
• Able and willing to provide written informed consent. This document must also actually be presented at the time of inclusion.
• For patients who decide to join the biopsy sub-study at sites selected for skin biopsy collection:beable and willing to provide skin biopsies at Baseline and Day113.(Week 16). |
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| E.4 | Principal exclusion criteria |
1.Treatment with any of the following prior to first IMP administration (Baseline):
•Systemic corticosteroids, and systemic calcineurin inhibitors (tacrolimus and cyclosporin) within 4 weeks;
•Leukotriene inhibitors within 4 weeks
•Systemic therapy for AD, including but not limited to methotrexate, cyclosporine, azathioprine, phosphodiesterase type 4 (PDE4)-inhibitors, IFN-γ and mycophenolate mofetil within 4 weeks;
•Targeted biologic and small molecule treatments within 5 half-lives or within 12 weeks prior to baseline, whichever is longer;
•Previous treatment with systemic janus kinase (JAK)inhibitors at any point.
•Topical corticosteroids, tacrolimus or pimecrolimus, or topical PDE4 within 7 days
•Prescription or non-prescription moisturisers with additives (e.g.urea, filaggrin) within 2 weeks;
•Phototherapy or allergen immunotherapy within 4 weeks
•Regular use (>2visits/week) of a tanning booth/parlour within 4 weeks
•Any prior use of anti OX40 or anti OX40L mAb; including KY1005.
•Investigational therapy for the treatment of AD or other conditions within 5 half-lives or the limit of PD effects or 12 weeks where the t1/2 is unknown.
2. Known history of, or suspected, significant current immunosuppression, including history of invasive opportunistic or helminth infections despite infection resolution or otherwise recurrent infections of abnormal frequency or prolonged duration.
3. Weight <40 kg or>150 kg at Baseline.
4. Treatment with a live (attenuated) immunisation within 12 weeks prior to Baseline; completion of required administrations of COVID-19 vaccine within 14 days prior to Baseline or within 14 days immediately prior to or following IMP administration.
5.Men and women (of reproductive potential) unwilling to use birth control and women who are pregnant or breastfeeding.
6.Any malignancies or history of malignancies prior to Baseline(except for non-melanoma skin cancer that has been excised and cured for more than 3years prior to Baseline;in situ cervical carcinoma that has been excised and cured).
7.Positive for human immunodeficiency virus, hepatitis B surface antigen, hepatitis B core antibody or hepatitis C antibody at the Screening Visit.
8. History (within last 2 years prior to Baseline) of prescription drug or substance abuse, including alcohol, considered significant by the Investigator.
9. Current or any past history of tuberculosis or non-tuberculous mycobacterial infections (including a positive QuantiFERON®-Tuberculosis Gold blood test at the Screening Visit).
10.Elective surgery planned to be scheduled for any time in the period from Screening up to 12 weeks following the last dose of IMP that in the investigator’s opinion would impact the conduct of the trial.
11.Anticipated initiation of prohibited medications from Screening up to 12 weeks following the last dose of IMP.
12.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, hypertension, renal disease, neurological conditions, heart failure and pulmonary disease.
13.Skin comorbidity that would adversely affect the ability to undertake AD assessments.
14.Any medical or psychiatric condition which, in the opinion of the investigator may present an unreasonable risk to the study patient as a result of his/her participation in this clinical study, may make patient’s participation unreliable, or may interfere with study assessments.
15.Any active or chronic infection requiring systemic treatment within 2 weeks prior to Baseline (1 week in the event of superficial skin infections).
16 Laboratory values at the Screening Visit:
•Serum creatinine>1.6 mg/dL(141μmol/L) in female patients and >1.9mg/dL(168 μmol/L) in male patients
•ALT or AST>2.0x ULN •Serum total bilirubin >1.5 x ULN (except for subjects with Gilbert’s syndrome, where total bilirubin must not exceed 3.0 mg/dL or 50μmol/L)
•In the Investigator’s opinion, any additional clinically significant laboratory results from the clinical chemistry, haematology or urinalysis tests at the Screening visit.
17.In the Investigator’s opinion, any significant abnormality on 12-lead ECG at the Screening Visit.
18.History of or known or suspected hypersensitivity to KY1005 or the matching placebo formulation, or excipients used in the presentation of KY1005 or placebo, or in preparation for administration. History of or known or suspected severe hypersensitivity reactions to other mAbs and/or their excipients.
19.Patients for whom coercion by either the Investigator or the Sponsor cannot be discounted.
(No patients will be included who are related to, or in a relationship with, or employed by the Investigator, the Sponsor or any organisations contracted on behalf of the Sponsor in the design, setting up or running of the study).
20.Concurrent participation in any other clinical study, including noninterventional studies. |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| Percentage change in EASI from Baseline to Day 113. |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
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| E.5.2 | Secondary end point(s) |
-Safety endpoints:
•Incidence of treatment emergent adverse events including AESIs.
-Pharmacokinetic endpoints:
•Serum KY1005 concentration assessed throughout the study for each patient (receiving KY1005).
-Key secondary efficacy endpoints:
•Percentage change from Baselinein EASI at Day 169.(Week 24).
•Percentage of patients with at least a 75% reduction from Baselinein EASI (EASI 75) at Days 113 (Week 16) and 169.(Week 24).
•Percentage of patients with a response of IGA 0 or 1 and a reduction from Baseline of ≥2 points at Days 113 (Week 16) and 169.(Week 24).
•Proportion of patients with improvement (reduction) ofweekly average of pruritus NRS ≥4 with a Baseline pruritis NRS of ≥4 from Baseline to Days113 (Week 16) and 169.(Week 24).
-Other secondary efficacy endpoints:
•Absolute change from Baselinein EASI at Days15,(Week 2),29,(Week 4),57,(Week 8),85,(Week 12),113,(Week 16),141 (Week 20) and 169.(Week24).
•Percentage change from Baseline in EASI at Days 15,(Week 2),29,(Week4),57,(Week 8),85 (Week 12) and 141.(Week 20).
•Percentage of patients with at least a 50% reduction fromBaselinein EASI (EASI 50) at Days 15,(Week 2),29,(Week 4),57,(Week 8),85,(Week 12),113,(Week 16),141 (Week 20) and 169.(Week 24).
•Percentage of patients with at least a 75% reduction from Baselinein EASI (EASI 75) at Days 15,(Week 2),29,(Week 4),57,(Week 8),85 (Week 12) and 141.(Week 20).
•Percentage of patients with at least a 90% reduction from Baselinein EASI (EASI 90) at Days 15,(Week 2),29,(Week 4),57,(Week 8),85,(Week 12),113,(Week 16),141 (Week 20) and 169.(Week 24).
•Percentage of patients with a 100% reduction from Baselinein EASI (EASI100) at Days 15,(Week 2),29,(Week 4),57,(Week 8),85,(Week 12),113,(Week 16),141 (Week 20) and 169.(Week 24).
•Change in IGA from Baseline to Day113(Week 16)and over time.
•Percentage of patients with a response of IGA 0 or 1 and a reduction from Baseline of ≥2 points at Days 15,(Week 2),29,(Week 4),57,(Week 8),85(Week 12)and 141.(Week 20).
•Absolute and percentage change in SCORAD Index from Baseline to Day169 (Week 24) and over time.
•Absolute and Percentage change in affectedBSA from Baseline to Day169 (Week 24) and over time.
•Absolute and Percentage change in POEM from Baseline to Day169 (Week24) and over time.
•Absolute and Percentage change in DLQI from Baseline to Day169 (Week24) and over time.
•Absolute and Percentage change in ADCT from Baseline to Day 169 (Week24)and over time.
•Absolute and Percentage change in HADS from Baseline to Day169(Week24)and over time.
•Absolute and Percentage change in weekly average of pruritus NRS from Baselineto Day 169 (Week 24) and over time. •Proportion of patients with improvement (reduction) of weekly average of pruritus NRS ≥3 with a Baseline pruritis NRS of ≥3 from Baseline to Days113 (Week 16) and 169.(Week 24).
-PD endpoints:
•Anti-KY1005 antibody titre and number of patients with positive response. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
-Safety endpoint: TEAEs & AESIs throughout study. -PK endpoint: Serum KY1005 conc throughout study.
-Key secondary efficacy endpoints:
• % change from Baseline in EASI at Days 169.
• %age of patients with EASI-75 at Days 113 and 169.
• % of patients with IGA 0 or 1 & a reduction from Baseline of ≥ 2 points at Days 113 & 169.
• Proportion of patients with improvement weekly average of pruritus NRS ≥ 4 with Baseline pruritis NRS of ≥ 4 from Baseline to Days 113 and 169.
-Other secondary efficacy endpoints: See above Section E.5.2 |
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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 | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
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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 | Yes |
| E.8.2.3.1 | Comparator description |
| Other doses and dose schedules KY1005 |
|
| E.8.2.4 | Number of treatment arms in the trial | 5 |
| 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 | 19 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 50 |
| 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 |
| Japan |
| United States |
| Bulgaria |
| Germany |
| Hungary |
| Poland |
| Spain |
| Taiwan |
| United Kingdom |
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| 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
|
| Last subjects last visit. |
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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 | 2 |
| E.8.9.1 | In the Member State concerned months | 1 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 8 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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