A clinical trial evaluating the efficacy and safety of the drugs - cyclosporine and methotrexate in children and adolescents with moderate to severe atopic dermatitis.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medical University Of Lodz

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

15 Mar 2021 → ongoing

Decision date (initial)

2024-12-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Agencja Badań Medycznych

External identifiers

EU CT number

2023-509759-15-00

EudraCT number

2020-004194-51

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

The main objective of the study is to compare the efficacy and safety of cyclosporine and methotrexate in children and adolescent subjects with moderate-to-severe atopic dermatitis.

Secondary objectives 3

1. To assess the efficacy of MTX or CsA monotherapy compared to standard of care on skin lesions improvement and subjective parameters (itch and quality of sleep) and health-related quality of life
2. To assess the safety and tolerability of MTX and CsA compared to standard of care.
3. To assess the period of clinical remission after treatment cessation at week 32.

Conditions and MedDRA coding

atopic dermatitis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. At the moment of giving written informed consent the patient must be between 2-18 y.o.
2. Diagnosis of moderate or severe AD established at least 6 months before baseline. Moderate-to-severe AD (EASI>16, BSA>10, SCORAD>25) must be confirmed based on clinical features on the screening and baseline visits.
3. The patient, according to doctor’s opinion, is a candidate for systemic therapy.
4. Body weight of the participant is within 3 and 97 percentile grid, matched for sex and age.
5. Female and male participants may be included. The participants who reached sexual maturity must be willing and give permission to use contraceptives or, together with the parent(s)/legal guardian(s), give a written agreement on sexual abstinence for the whole duration of clinical trial and within 6 months after cessation of IMP. In females with childbearing potential (defined as Tanner stage ≥3 or menarche), a pregnancy test must be performed at screening and baseline visit to rule out pregnancy. Pregnancy tests will be performed according to schedule.
6. Within 2 weeks before administration of the first drug dose the patient can use only topical emollients.
7. The participant, parent(s)/legal guardian(s) are willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
8. The participant, parent(s)/legal guardian(s) give permission to avoid excessive exposure to natural or artificial sunlight (solaria) during the course of clinical trial.
9. The medications taken by the participants because of other causes than AD, must be in stable doses within 2 weeks or 5 half-lives (whichever is longer) prior to the screening visit.
10. The participant, parent(s)/legal guardian(s) must be willing and give permission to use only one emollient during the clinical trial, provided by the Sponsor.
11. The patient must be vaccinated according to national regulations, the last vaccination at least one month before the first dose of IMP (8 weeks in case of live vaccine). There are no contraindications to vaccination with live vaccines if the patient is in the standard of care arm and 12 weeks after the end of treatment in the arm with CsA and MTX.

Exclusion criteria 23

1. The participant suffers from any acute or chronic disease or has abnormal laboratory tests results which could increase the risk of the trial medical intervention and which, according to the Investigator’s opinion, could interfere with the treatment and obscure the interpretation of the results or which make the subject otherwise ineligible to take part in the clinical trial.
2. The presence of any psychiatric disorder, alcohol abuse, drug dependency in the participant or in the participant’s parent(s)/legal guardian(s), which in the Investigator’s opinion may make them unable to take part in the clinical trial and to comply with the trial protocol.
3. Current clinically significant infection or a history of a clinically significant infection including herpes simplex infection, within 3 months prior to baseline visit which, in the opinion of the Investigator or Sponsor’s medical expert, may compromise the safety of the subject in the trial, interfere with evaluation of the IMP, or reduce the subject’s ability to participate in the trial. Clinically significant infections, are defined as: a systemic infection and/or a serious skin infection requiring parenteral (intravenous or intramuscular) antibiotics, antiviral, or antifungal medication.
4. History of any active skin infection within 1 week prior to baseline visit.
5. Positive test for HIV.
6. Positive hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis B core antibody (HBcAb) or hepatitis C virus antibody (anti-HCV) serology at screening. Subjects with positive HBsAb may be randomized provided they are hepatitis B vaccinated and have negative HBsAg and HBcAb.
7. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥2.0 times the upper limit of normal (ULN) at screening.
8. Immune disorders which may, in the opinion of the Investigator, comprise the safety of the subject in the trial or interfere with evaluation of the IMP.
9. Active or latent tuberculosis or improperly treated tuberculosis, proven with QuantiFERON TB Gold test performed on the screening visit or within 12 weeks before the baseline visit. Chemoprophylaxis in accordance with local guidelines may enable re-screening.
10. Immunosuppressive treatment or use of systemic steroids within 4 weeks before the first dose of IMP.
11. Use of phototherapy within 2 weeks prior to baseline visit or PUVA-therapy within 4 weeks prior to baseline visit.
12. Use of topical steroids or topical calcineurin inhibitors within two weeks before baseline visit.
13. Participation in this and any other clinical trial involving investigational drug(s) within 8 weeks or within 5 half-lives (if known) whichever is longer, prior to clinical trial entry and/or during trial participation.
14. Use of MTX or CsA within 6 months prior to baseline visit.
15. Known or suspected hypersensitivity to any component of the IMP.
16. History of cancer: Subjects who have had any malignancies are eligible provided that the subject is in remission and curative therapy was completed at least 5 years prior to the date informed consent was obtained.
17. Any disorder which is not stable and in the Investigator’s opinion could: affect the safety of the subject throughout the trial, interfere with the evaluation of the IMP or, impede the subject’s ability to complete the clinical trial. Examples include but are not limited to cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, immunological, and psychiatric disorders and major physical impairment.
18. Any abnormal finding which in the Investigator’s opinion may put the subject at risk because of their participation in the trial, influence the results of the trial, influence the subject’s ability to complete the trial.
19. Subjects with strong fear of drawing blood or unwilling to comply with the assessments scheduled during the trial.
20. Subject or subject’s parent(s)/legal guardian(s) have a language barrier, mental incapacity, unwillingness or lacking ability to understand the trial-related procedures.
21. Subjects who are legally institutionalised.
22. Employees of the Clinical Trial Site or any other individuals directly involved with the planning or conduct of the trial, or immediate family members of such individuals.
23. Subject who has received any live vaccination within the 8 weeks prior to Baseline Visit. Live vaccines are not allowed during the trial until 12 weeks after last dose IMP.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of patients achieving 75% improvement in EASI (EASI75) from baseline at week 32.

Secondary endpoints 22

1. Proportion of patients achieving 75% improvement in EASI (EASI75) from baseline at week 16.
2. Percent change in EASI score from baseline to week 16.
3. Percent change in EASI score from baseline to week 32.
4. Proportion of patients with Investigator’s Global Assessment (IGA) 0 (clear) or 1 (almost clear) at week 16.
5. Proportion of patients with Investigator’s Global Assessment (IGA) 0 (clear) or 1 (almost clear) at week 32.
6. Change in Scoring Atopic Dermatitis (SCORAD) from baseline to week 16
7. Change in Scoring Atopic Dermatitis (SCORAD) from baseline to week 32.
8. Itch Reduction of Pruritus in numeric rating scale (NRS) and in VAS (visual analogue scale) from baseline to Week 16.
9. Itch Reduction of Pruritus in numeric rating scale (NRS) and in VAS (visual analogue scale) from baseline to Week 32.
10. Change in Children’s Dermatology Life Quality Index (CDLQI) score from baseline to Week 16.
11. Change in Children’s Dermatology Life Quality Index (CDLQI) score from baseline to Week 32
12. Change in Family Dermatology Life Quality Index (FDQL) from baseline to week 16.
13. Change in Family Dermatology Life Quality Index (FDQL) from baseline to week 32.
14. Change in Infant’s Dermatitis Quality of Life (IDQI) from baseline to week 16.
15. Change in Infant’s Dermatitis Quality of Life (IDQI) from baseline to week 32.
16. Change in Patient-Oriented Eczema Measure (POEM) from baseline to week 16.
17. Change in Patient-Oriented Eczema Measure (POEM) from baseline to week 32.
18. Incidence of treatment-emergent AE from baseline through week 16.
19. Incidence of treatment-emergent AE from baseline through week 32.
20. Incidence of treatment-emergent AE leading to treatment discontinuation from baseline through week 16.
21. Incidence of treatment-emergent AE leading to treatment discontinuation from baseline through week 32.
22. Time to exacerbation of AD (loss of at least 50% of the EASI response at week 32) after treatment cessation at week 32.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 8

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medical University Of Lodz

Sponsor organisation

Medical University Of Lodz

Address

Al. Tadeusza Kosciuszki 4

City

Lodz

Postcode

90-419

Country

Poland

Scientific contact point

Organisation

Medical University Of Lodz

Contact name

Joanna Narbutt

Public contact point

Organisation

Medical University Of Lodz

Contact name

Paulina Czernicka

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Urgent safety measures 1 · Art. 54 CTR

Unexpected events 1 · Art. 53 CTR

Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 37 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications