Investigator initiated clinical trial of dantrolene as a treatment for Darier disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Karolinska University Hospital

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

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

Trial duration

7 Nov 2024 → 10 Sep 2025

Decision date (initial)

2024-11-07

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

External identifiers

EU CT number

2024-519201-36-00

EudraCT number

2020-004281-19

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

To evaluate if dantrolene treatment reduce skin area affected.

Secondary objectives 5

1. if dantrolene treatment improve patient quality of life, mood and treatment satisfaction.
2. if dantrolene treatment improve skin
3. safety of dantrolene treatment in subjects with DD.
4. if dantrolene treatment affect skin quality on the microscopic and molecular level.
5. if new disease severity scale can be used for DD.

Conditions and MedDRA coding

Darier disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. The inclusion criteria will be histopathologically verified diagnosis combined with typical skin symptoms of hyperkeratotic papules and erythema (1), or clinical symptoms combined with family history in which the relative has a histopathologically verified diagnosis (2). Specifically, we will only include patients with a Physician Global Assessment of at least 3. Written consent to participate in the study will also be an inclusion criterion as well as age at least 18 years.

Exclusion criteria 17

1. Liver disease including steatosis, cirrhosis and hepatitis B/C (contraindication)
2. Wheat allergy (contraindication)
3. Hypersensitivity to the active substance or to any filling material (contraindication)
4. Rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption (contraindication)
5. Whenever spasticity is utilized to obtain or maintain increased function (contraindication)
6. Pregnancy, breastfeeding, or planned pregnancy.
7. Recent acute illness (past 4 weeks)
8. Active substance abuse
9. Kidney disease
10. Heart failure
11. Pulmonary disease such as COPD (but not common asthma)
12. Abnormal blood chemistry (assessed by blood samples)
13. Known or suspected allergies against dantrolene or vehicle
14. Systemic treatment for Dariers disease that cannot be paused during the study (e.g. acitretin)
15. Mental inability, reluctance or language difficulties that result in difficulty understanding the meaning of study participation
16. Participation or recent participation in a clinical study with an investigational product (within 30 days).
17. Concomitant Medication that may interact (taken at least bi-weekly for medications taken on a daily basis or at all for depo medications): antihistamines (e.g., cetirizine, doxylamine, diphenhydramine, hydroxyzine, loratadine), antipsychotics (e.g., chlorpromazine, clozapine, haloperidol, olanzapine, quetiapine, risperidone), apalutamide, benzodiazepines (e.g., alprazolam, diazepam, lorazepam), bosentan, brimonidine, buspirone, calcium channel blockers (e.g., amlodipine, diltiazem, verapamil), cannabis, chloral hydrate, dabrafenib, dexamethasone, efavirenz, enzalutamide, etravirine, methadone, mirtazapine, mitotane, modafinil, muscle relaxants (e.g., baclofen, cyclobenzaprine, methocarbamol, orphenadrine), nabilone, narcotic pain relievers (e.g., codeine, fentanyl, morphine, oxycodone), pramipexole, rifabutin, rifampin, ropinirole, rotigotine, St. John's wort, scopolamine, seizure medications (e.g., carbamazepine, clobazam, levetiracetam, phenobarbital, phenytoin, primidone, topiramate, valproic acid, zonisamide), selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, fluoxetine, paroxetine, sertraline), siltuximab, sodium oxybate, tapentadol, thalidomide, tocilizumab, tramadol, tricyclic antidepressants (e.g., clomipramine, desipramine, imipramine), zolpidem, zopiclone

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint will be a reduction of skin area affected using the 5-point Physician Global Assessment (PGA) scale (23). A 20 % reduction (1 point) will be considered the minimal clinically important difference.

Secondary endpoints 3

1. As the main secondary endpoint, improvement in dermatological quality of life index (DLQI) will be used. A 4 points improvement in DLQI will be considered the minimal clinically important difference (24). We will also examine mood with the Montgomery–Åsberg Depression Rating Scale (MADRS) and treatment satisfaction with the Treatment Satisfaction Questionnaire for Medication (TSQM).
2. As complementary skin assessment tools we will use the Eczema Area and Severity Index (EASI) scale and Body Surface Area (BSA).
3. Number of adverse events and adverse reactions, serious and non-serious.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Karolinska University Hospital

Sponsor organisation

Karolinska University Hospital

Address

Eugeniavagen 3

City

Solna

Postcode

171 64

Country

Sweden

Scientific contact point

Organisation

Karolinska University Hospital

Contact name

Dr Jakob Wikström

Public contact point

Organisation

Karolinska University Hospital

Contact name

Dr Jakob Wikström

Third parties 1

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

Results and documents

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

Documents 4 files

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

Application history

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