Severe Erythema Multiforme - CORTICO

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

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

Decision date (initial)

2024-09-04

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

French Ministry of Health (PHRC N 2019)

External identifiers

EU CT number

2024-516018-39-00

EudraCT number

2022-000712-59

ClinicalTrials.gov

NCT06266221

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

To demonstrate that a short course (12 days) of SCS could alleviate pain and improve food intake without rescue therapy, as compared with placebo in the acute established phase of severe EM.

Secondary objectives 10

1. Evaluate the impact of SCS on the duration of clear or almost clear healing of all sites
2. Evaluate the impact of SCS on the duration of fever
3. Compare the length of hospital stay between the two groups
4. Compare the consumption of level III analgesics between the two groups
5. Compare the pain intensity between the two groups
6. Compare chopped or solid food intake resumption between the two groups
7. Compare the rate of rescue therapies (IV methylprednisolone at 1mg/kg/day with discontinuation of the current treatment in both arms) between the two groups
8. Evaluate the impact of SCS on the rate of sequelae (affecting eyes, oral cavity, genital area, esophagus, respiratory tract)
9. Compare the rate of adverse events between the two groups
10. Evaluate the quality of life

Conditions and MedDRA coding

Erythema multiforme (EM) in its severe form managed at the hospital

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Age ≥ 15 years old and 30 kg ≤ Weight ≤ 150 kg
2. Clinical diagnosis of severe EM defined as: o Typical skin lesions if first flare of EM: raised target lesions with 2 or 3 concentric rings located on the extremities or disseminated. In case of recurrent EM, with proven anterior flare (known clinical diagnosis associating typical skin lesions and MM involvement in a previous flare), typical skin lesions are not essential for inclusion, because EM may manifest as isolated mucosal involvement. o Two or more MMs affected (mouth, throat, eyes, ear, nose, genital and/or anal areas), or only the oral MM affected, if severely affected (score* 2 or 3 of Harman criteria) with altered general conditions and significant impact on food intake (solid food impossible). (* Oral score: 1, minor activity (up to three erosions); 2, moderate activity (more than three but less than 10 erosions, or generalized desquamative gingivitis); 3, severe (more than 10 discrete erosions or extensive, confluent erosions, or generalized desquamative gingivitis with discrete erosions at other oral sites)).
3. First flare of EM or acute recurrence of previously diagnosed EM
4. Disease flare that has lasted for up to 5 days (≤5 days)
5. Affiliated with a social security scheme
6. Able to provide written informed consent; the consent of both parents will be collected for minors.

Exclusion criteria 17

1. EM without involvement of oral cavity compromising normal solid food
2. Patients unable to eat solid food outside of their current pathology (erythema multiforme)
3. Other diagnosis potentially involving MMs: Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), pemphigus, herpetic gingivostomatitis
4. Systemic Corticosteroids prescribed for another disease on inclusion day (any dose)
5. Use of systemic Corticosteroids for > 5 days for any previous flare of EM (>10mg)
6. Contraindication to systemic Corticosteroids: o hypersensitivity to systemic Corticosteroids or to an excipient o uncontrolled primary bacterial, viral, fungal or parasitic infections o psychotic states not yet controlled by treatment
7. Sepsis (shock, cyanosis, hypothermia, low blood pressure monitored successively twice (systemic blood pressure < 90 mmHg and diastolic blood pressure < 60 mmHg)
8. Kidney or liver insufficiency (creatinine level ≥ 150 μmol/L; aspartate aminotransferase or alanine aminotransferase level > 3 times the upper limit of normal)
9. Current cancer with the exception of non-metastatic skin carcinoma not requiring immediate medical treatment
10. Pregnant or breastfeeding
11. Person subject to safeguards of justice, deprived of liberty by judicial or administrative decision
12. Person subject to psychiatric care without their consent
13. Person admitted to a health or social establishment for purposes other than those of research
14. Person unable to express their consent
15. Person under legal protection (guardianship or curatorship)
16. Participation in another clinical trial (medicinal products trials) or in the exclusion period at the end of a previous clinical trial concerning medicinal products, if applicable
17. (person) on state medical aid

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The time to success defined by controlled pain (Nu-meric Rating Scale (NR, range 0-10) score <4 and sustained no need for any level III analgesics, during 48 hours), resumption of chopped or solid food intake and no need for rescue therapy (IV methylprednisolone at 1mg/kg/day with discontin-uation of the current treatment in both arms).

Secondary endpoints 10

1. Time to clear or almost clear healing of all sites (“clear” is defined as no erosion or skin ulceration and absence of new lesions and “almost clear” is defined as “presence of 1, or 2 maximum, micro erosions / punctiform millimetric erosions, and absence of new lesions”). Healing will be evaluated by the clinician daily.
2. Time to fever resolution (fever resolution defined as absence of fever (temperature ≤ 37,8° C) for at least 24h)
3. Length of hospital stay
4. Number of days of consumption of level III analgesics at least once in the day
5. Pain will be assessed three times a day during hospitalization and once a day (worst score of the day) after the hospitalization until achievement of the primary endpoint
6. Chopped or solid food intake resumption evaluated with daily food intake evaluation (cf. Appendix 4 of Protocol)
7. Rate of patients in the two groups with need for a rescue therapy (IV methylprednisolone at 1mg/kg/day with discontinuation of the current treatment in both arms)
8. Taux de séquelles (cutanées et muqueuses (séquelles oculaires, ORL, oesophagiennes, pulmonaires et génitales) évaluées cliniquement à 3 mois (M3) et 6 mois (M6)
9. Rate of adverse events during the treatment and follow-up
10. Evaluation of the quality of life with the use of Patient Global Impression of Change (PGIC), scale on 7 points, at the end of hospitalization, D7, D15, M1 and in case of relapse

Investigational products

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

Test 2

Placebo 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Saskia ORO

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Saskia ORO

Locations

1 EU/EEA country · 22 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 13 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