Safety Study of Elidel (Pimecrolimus) 1% Cream to Treat Netherton Syndrome

• Sponsor: Children's Hospital of Philadelphia (Other)
• Overall Status: Completed
• CT.gov ID: NCT00208026
• Collaborator: Novartis Pharmaceuticals (Industry)
• Enrollment: 3
• Location: 1
• Arm: 1
• Duration (Months): 30
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Netherton syndrome is a genetic condition that can result in abnormal skin functioning. People with this condition often have red and scaling skin; sparse or short hair; and problems with absorption of medicines or chemicals that are applied to the skin. If these chemicals are absorbed at a high level, they may cause health problems. Elidel (pimecrolimus) is a new medicine that is available as a cream. It has been shown to help improve the appearance of the skin in patients with another skin condition known as atopic dermatitis, and is approved by the United States (US) Food and Drug Administration for use in children with mild to moderate atopic dermatitis. The purpose of this study is to determine if Elidel is safe, to see whether the medication is absorbed through the skin, and to see if side effects are associated with its use in children with Netherton syndrome.

Condition or Disease	Intervention/Treatment	Phase
Netherton Syndrome	Drug: Pimecrolimus 1% Cream	Phase 1/Phase 2

Detailed Description

Patients with Netherton syndrome, a rare genodermatosis, manifest a chronic, eczematous dermatitis with erythema and scaling that is often recalcitrant to conventional therapy with emollients and topical corticosteroids. These patients display an altered epidermal barrier with increased permeability to topical agents and are therefore susceptible to evaporative transepidermal water loss and infection. Topical therapy with the calcineurin inhibitors tacrolimus and pimecrolimus has been demonstrated to improve the skin integrity and the quality of life of patients with several chronic dermatoses, including atopic dermatitis. As a result of the underlying skin barrier dysfunction, however, the possibility of significant systemic absorption and resultant side effects is a concern when these agents are used in patients with Netherton syndrome. Experience with topical tacrolimus 0.1% ointment for patients with Netherton syndrome has demonstrated both marked efficacy as well as significant systemic absorption of the drug in this patient population. Use of topical pimecrolimus in patients with Netherton syndrome has not been reported to date. Investigation of the extent of systemic absorption and side effects will help to define the safety and efficacy profile of topical pimecrolimus in patients with Netherton syndrome.

Study Design

• Study Type: Interventional
• Actual Enrollment: 3 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Exploratory Safety and Systemic Absorption of Elidel (Pimecrolimus) 1% Cream for the Treatment of Netherton Syndrome
• Study Start Date: Sep 1, 2005
• Actual Primary Completion Date: Mar 1, 2008
• Actual Study Completion Date: Mar 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pimecrolimus 1% Cream Treatment with drug/Elidel. Single arm-open-label treatment arm. A Pilot Study of the Efficacy and Safety of Pimecrolimus Cream 1% for the Treatment of Netherton Syndrome:	Drug: Pimecrolimus 1% Cream; Open label single arm; Other Names: Elidel Eczema

Outcome Measures

Primary Outcome Measures

1. Blood Pimecrolimus Levels [Each visit up to 18 months: Study Days 1, 7, 14, 28, 56, 84, 175, 360, and 520]

   At each scheduled visit, blood concentration of pimecrolimus were obtained. This value reflects the amount of pimecrolimus in the blood. This is measured directly from the blood and provides an estimate of the degree of absorption of the treatment medication through the skin into the blood.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 18 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Clinical diagnosis of Netherton syndrome

• Normal laboratory values within 3 months prior to enrollment

• Signed written informed consent

• Willingness and ability to comply with the study requirements

• For women of childbearing age, negative urine pregnancy test at enrollment and then monthly thereafter; women of childbearing age who are not abstinent must use contraception.

Exclusion Criteria:

• Clinically significant physical examination or laboratory abnormalities

• Clinical evidence of liver disease or liver injury as documented by abnormal liver function tests

• Symptoms of a significant acute illness in the 30 week period preceding the start of treatment

• Patients with known serious adverse reactions or hypersensitivity to macrolides or calcineurin inhibitors or with known hypersensitivity to any of the ingredients of the study medication or history of adverse reactions to the anesthetic product used for blood draws

• Topical tacrolimus or Elidel within 2 weeks prior to dosing

• Systemic steroid, systemic tacrolimus, or any immunosuppressant within 1 month prior to dosing

• Phototherapy within 1 month prior to dosing

• Use of inhibitors of Cytochrome P450 3A4 (CYP3A4) iso-enzyme within 2 weeks prior to dosing

• Topical steroids or other topical therapy (except tacrolimus) may be used up to the day of 1st application of Elidel; however, treatment must be discontinued during the treatment period. Topical treatment of corticosteroids may resume immediately after the treatment period or in case an alert value has been exceeded and the Elidel treatment will be continued only on the face and neck.

• Participation in any clinical trials within 2 months prior to dosing

• History or clinical evidence of cardiovascular, respiratory, renal, hepatic, gastrointestinal, hematologic, neurologic disease, or any disease other than Netherton syndrome, that may put the subject at undue risk. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of drugs.

• History of presence of malignancy or lymphoproliferative disease

• Presence of any viral or fungal or untreated bacterial skin infection

• Known HIV positivity or active hepatitis B or C

• History of immunocompromise

• No vaccines containing live viruses are to be administered during the study period.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• Children's Hospital of Philadelphia
• Novartis Pharmaceuticals

Investigators

• Principal Investigator: Albert C Yan, MD, Children's Hospital of Philadelphia

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Children's Hospital of Philadelphia
• Foundation for Ichthyosis and Related Skin Types

Publications

None provided.

• Responsible Party: Albert Yan, Principal Investigator, Children's Hospital of Philadelphia
• ClinicalTrials.gov Identifier: NCT00208026
• Other Study ID Numbers: 2004-11-4063
• First Posted: Sep 21, 2005
• Last Update Posted: Aug 14, 2019
• Last Verified: Jul 1, 2019

• Additional relevant MeSH terms: Netherton Syndrome; Syndrome; Pimecrolimus

Study Results

Participant Flow

Recruitment Details	This was an open-label,single-arm study to investigate the safety profile of topical pimecrolimus cream. Patients meeting the criteria for diagnosis of Netherton Syndrome were enrolled over a period of 3 years, from September 2005 through March 2008. The study was conducted in my medical office within The Children's Hospital of Philadelphia.
Pre-assignment Detail	The eligibility was for male and female patients aged 2 to 18 years.They were required to have normal laboratory values within 3 months prior to enrollment. A 4 week washout period was required for systemic steroid, tacrolimus, immunosuppressives, phototherapy, and inhibitors of Cytochrome. 2 week washout for Isoenzyme,tacrolimus and pimecrolimus.

Arm/Group Title	Elidel (Pimecrolimus) 1% Cream
Arm/Group Description	Treatment with drug/Elidel.Single arm-open-label treatment arm. A Pilot Study of the Efficacy and Safety of Pimecrolimus Cream 1% for the Treatment of Netherton Syndrome:
Period Title: Overall Study
STARTED	3
COMPLETED	3
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Elidel (Pimecrolimus) 1% Cream
Arm/Group Description	Treatment with drug/Elidel.Single arm-open-label treatment arm. A Pilot Study of the Efficacy and Safety of Pimecrolimus Cream 1% for the Treatment of Netherton Syndrome:
Overall Participants	3
Age (Count of Participants)
<=18 years	3 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	3 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	3 100%

Outcome Measures

1. Primary Outcome

Title	Blood Pimecrolimus Levels
Description	At each scheduled visit, blood concentration of pimecrolimus were obtained. This value reflects the amount of pimecrolimus in the blood. This is measured directly from the blood and provides an estimate of the degree of absorption of the treatment medication through the skin into the blood.
Time Frame	Each visit up to 18 months: Study Days 1, 7, 14, 28, 56, 84, 175, 360, and 520

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patient 1	Patient 2	Patient 3
Arm/Group Description	Treatment with drug/Elidel. Single arm-open-label treatment arm. A Pilot Study of the Efficacy and Safety of Pimecrolimus Cream 1% for the Treatment of Netherton Syndrome: Pimecrolimus 1% Cream: Open label single arm	Treatment with drug/Elidel. Single arm-open-label treatment arm. A Pilot Study of the Efficacy and Safety of Pimecrolimus Cream 1% for the Treatment of Netherton Syndrome: Pimecrolimus 1% Cream: Open label single arm	Treatment with drug/Elidel. Single arm-open-label treatment arm. A Pilot Study of the Efficacy and Safety of Pimecrolimus Cream 1% for the Treatment of Netherton Syndrome: Pimecrolimus 1% Cream: Open label single arm
Measure Participants	1	1	1
Day 1	0	0	0.312
Day 7	1.260	0.625	3.630
Day 14	0.821	0.421	3.930
Day 28	0.592	0.311	7.080
Day 56	0.743	0.182	3.920
Day 84	0.390	0.368	5.010
Day 175	0.470	0.484	2.060
Day 360	0.388	0.247	4.280
Day 520	0.224	0.170	6.140

Adverse Events

Time Frame	During the 18 month study, all 3 patients were evaluated throughout the study.
Adverse Event Reporting Description	No serious adverse events were reported.
Arm/Group Title	Elidel (Pimecrolimus) 1% Cream
Arm/Group Description	Treatment with drug/Elidel.Single arm-open-label treatment arm. A Pilot Study of the Efficacy and Safety of Pimecrolimus Cream 1% for the Treatment of Netherton Syndrome:
All Cause Mortality
	Elidel (Pimecrolimus) 1% Cream
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Elidel (Pimecrolimus) 1% Cream
	Affected / at Risk (%)	# Events
Total	0/3 (0%)
Other (Not Including Serious) Adverse Events
	Elidel (Pimecrolimus) 1% Cream
	Affected / at Risk (%)	# Events
Total	0/3 (0%)

Limitations/Caveats

There were no early termination for any of the subjects.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.