| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
| Eczema (Atopic dermatitis) |
|
| 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 |
| To establish the efficacy of ruxolitinib cream in participants with AD (IGA). |
|
| E.2.2 | Secondary objectives of the trial |
Key secondary:
To further assess the treatment effects of ruxolitinib cream (EASI75; Itch NRS; PROMIS short form - sleep disturbance).
Secondary:
To evaluate the safety and tolerability of ruxolitinib cream.
To further evaluate efficacy of ruxolitinib cream.
To evaluate the participants' Quality of Life and other patient-reported outcomes.
To evaluate the pharmacokinetics of ruxolitinib cream in plasma. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Adolescents aged ≥ 12 to 17 years, inclusive, and men and women aged ≥ 18 years.
2. Participants diagnosed with AD as defined by the Hanifin and Rajka (1980) criteria.
3. AD duration of at least 2 years.
4. Participants with an IGA score:
a. VC period: 2 to 3 at screening and baseline
b. LTS period: 0 to 4 at Week 8
5. Participants with %BSA (excluding scalp) of AD involvement:
a. VC period: 3% to 20% at screening and baseline
b. LTS period: 0% to 20% at Week 8
6. Participants who agree to discontinue all agents used to treat AD from screening through the final follow-up visit.
7. Participants who have at least 1 "target lesion" that measures approximately 10 cm2 or more at screening and baseline. Lesion must be representative of the participant's disease state and not be located on the hands, feet, or genitalia.
8. Willingness to avoid pregnancy or fathering of children based on the criteria below:
a. Woman of nonchildbearing potential (surgically sterile with a hysterectomy and/or bilateral oophorectomy OR postmenopausal, defined by last menstrual period ≥ 12 months of amenorrhea before screening confirmed by FSH levels at screening) and at least 50 years of age) are exempt from pregnancy testing.
b. Woman of childbearing potential who has a negative serum pregnancy test at screening and a negative urine pregnancy test before the first dose on Day 1 and who agrees to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through safety follow-up (30 [+ 7] days after EOT). Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the participant and their understanding confirmed.
c. Adolescents who are prepubescent.
d. Man who agrees to take appropriate precautions to avoid fathering children (with at least 99% certainty) or from sperm donation from screening through 90 days after treatment with ruxolitinib cream. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the participant and their understanding confirmed.
9. Ability to comprehend and willingness to sign an ICF or written informed consent of the parent(s) or legal guardian and written assent from the participant when possible.
Note: Adolescent participants who become legal adults during the study will be asked for their signed consent to continue the study, and in the event of lack thereof, will be discontinued from further participation. |
|
| E.4 | Principal exclusion criteria |
1. Participants who have an unstable course of AD (spontaneously improving or rapidly deteriorating) as determined by the investigator in the 4 weeks prior to baseline.
2. Participants with concurrent conditions and history of other diseases:
a. Immunocompromised (eg, lymphoma, acquired immunodeficiency syndrome, Wiskott-Aldrich syndrome).
b. Chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks before baseline.
c. Active acute bacterial, fungal, or viral skin infection (eg, herpes simplex, herpes zoster, chicken pox) within 1 week before baseline.
d. Any other concomitant skin disorder (eg, generalized erythroderma such as Netherton syndrome), pigmentation, or extensive scarring that, in the opinion of the investigator, may interfere with the evaluation of AD lesions or compromise participant safety.
e. Presence of AD lesions only on the hands or feet without prior history of involvement of other classical areas of involvement such as the face or the folds.
f. Other types of eczema.
3. Any serious illness or medical, physical, or psychiatric condition(s) that, in the investigator's opinion, would interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data. For example:
a. Clinically significant or uncontrolled cardiac disease, including unstable angina, acute myocardial infarction within 6 months from Day 1 of study drug administration, New York Heart Association Class III or IV congestive heart failure, and arrhythmia requiring therapy or uncontrolled hypertension (blood pressure > 150/90 mmHg) unless approved by medical monitor/sponsor.
b. Participants with a history of malignancy in the 5 years preceding enrollment into this study, except for adequately treated, nonmetastatic malignancies.
c. Low hemoglobin (< 10 g/dL).
d. Severe renal disease on dialysis (serum creatinine > 2 mg/dL).
e. Current and/or liver disease history, including known hepatitis B or C, with hepatic or biliary abnormalities.
4. Participants using any of the following treatments within the indicated washout period before baseline:
a. 5 half-lives or 12 weeks, whichever is longer – biologic agents (eg, dupilumab).
b. 4 weeks – systemic corticosteroids or adrenocorticotropic hormone analogs, cyclosporin, methotrexate, azathioprine, or other systemic immunosuppressive or immunomodulating agents (eg, mycophenolate or tacrolimus).
c. 2 weeks – immunizations and sedating antihistamines, unless on long-term stable regimen (nonsedating antihistamines are permitted).
d. 1 week – use of other topical treatments for AD (other than bland emollients), such as corticosteroids, calcineurin inhibitors, coal tar (shampoo), antibiotics, antibacterial cleansing body wash/soap. Diluted sodium hypochlorite "bleach" baths are allowed as long as they do not exceed 2 baths per week and their frequency remains the same throughout the study.
5. Participants who have previously received JAK inhibitors, systemic or topical.
6. Ultraviolet light therapy or prolonged exposure to natural or artificial sources of UV radiation (eg, sunlight or tanning booth) within 2 weeks prior to baseline and/or intention to have such exposure during the study, which is thought by the investigator to potentially impact the participant's AD.
7. Positive serology test results at screening for HIV antibody.
8. Liver function tests: AST or ALT ≥ 2 × ULN; alkaline phosphatase and/or bilirubin > 1.5 × ULN (isolated bilirubin > 1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin < 35%).
9. Pregnant or lactating participants, or those considering pregnancy.
10. History of alcoholism or drug addiction within 1 year before screening or current alcohol or drug use that, in the opinion of the investigator, will interfere with the participant's ability to comply with the administration schedule and study assessments.
11. Current treatment or treatment within 30 days or 5 half-lives (whichever is longer) before baseline with another investigational medication or current enrollment in another investigational drug Protocol.
12. Participants who, in the opinion of the investigator, are unable or unlikely to comply with the administration schedule and study evaluations.
13. Participants who are committed to a mental health institution by virtue of an order issued either by the judicial or the administrative authorities.
14. Employees of the sponsor or investigator or are otherwise dependents of them. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Proportion of participants achieving IGA-TS at Week 8 |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
Key secondary:
• Proportion of participants who achieve EASI75 at Week 8.
• Proportion of participants with a ≥ 4-point improvement in Itch NRS score from baseline to Week 8.
• Proportion of participants with a clinically meaningful improvement in the PROMIS Short Form – Sleep Disturbance (8b) 24-hour recall score at Week 8.
Secondary:
• The frequency, duration, and severity of AEs; performing physical examinations; collecting vital signs; and collecting laboratory data for hematology, serum chemistry, and urinalysis.
• Proportion of participants achieving an IGA-TS at Weeks 2 and 4.
• Proportion of participants achieving an IGA of 0 or 1 at each visit.
• Proportion of participants with a ≥ 4-point improvement in Itch NRS score from baseline to Weeks 2 and 4.
• Proportion of participants who achieve EASI50 at each visit during the VC period.
• Proportion of participants who achieve EASI75 at Weeks 2 and 4.
• Proportion of participants who achieve EASI90 at each visit during the VC period.
• Mean percentage change from baseline in EASI score at each visit during the VC period.
• Mean percentage change from baseline in SCORAD score at each visit during the VC period.
• Change from baseline in Itch NRS score at each visit during the VC period.
• Time to achieve Itch NRS score improvement of at least 2, 3, or 4 points.
• Change from baseline in Skin Pain NRS score at each visit during the VC period.
• Proportion of participants with a clinically meaningful improvement in the PROMIS Short Form – Sleep-Related Impairment (8a) 24-hour recall score at Weeks 2, 4, and 8.
• Change from baseline in PROMIS Short Form – Sleep-Related Impairment (8a) 24-hour recall and Short Form – Sleep Disturbance (8b) 24-hour recall score at Weeks 2, 4, and 8.
• PROMIS Short Form – Sleep-Related Impairment (8a) 7-day recall and Short Form – Sleep Disturbance (8b) 7-day recall score at Weeks 8, 12, 24, and 52.
• Change from baseline in AD afflicted %BSA at every visit.
Quality of life endpoints:
• Change from baseline in POEM score at each visit.
• Change from baseline in DLQI score at Weeks 2, 4, 8, 12, 24, and 52 and at unscheduled visits.
• Mean PGIC score at Weeks 2, 4, and 8.
• Proportion of participants with each score on the PGIC at Weeks 2, 4, and 8.
• Proportion of participants with a score of either 1 or 2 on the PGIC at Weeks 2, 4, and 8.
• Change from baseline in EQ-5D-5L score during the VC period.
• Change from baseline in WPAI-SHP v2.0 at Weeks 2, 4, 8, 12, 24, 36, and 52.
• Pharmacokinetics: Trough plasma concentrations of ruxolitinib at all study visits. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Week 2, 4, 8, 12, 24, 52 and unscheduled visits |
|
| 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 | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| 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 |
| To evaluate the participants' Quality of Life |
|
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| 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 | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 34 |
| 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 |
| Bulgaria |
| Canada |
| Czech Republic |
| Germany |
| Poland |
| Spain |
| United States |
|
| 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 | 7 |
| 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 | 7 |
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