A Study Evaluating the Safety and Efficacy of Topical BPR277 for the Treatment of Atopic Dermatitis and Netherton Syndrome

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01428297
First received: August 19, 2011
Last updated: November 25, 2013
Last verified: November 2013
  Purpose

The study is divided in 3 parts, starting with the safety assessment of BPR277 ointment in Healthy volunteers (Part 1). If found to be well tolerated in Part 1, BPR277 ointment will be assessed in two different patients groups to evaluate safety and efficacy in atopic dermatitis (Part 2) and in Netherton syndrome (Part 3).


Condition Intervention Phase
Healthy Volunteers
Atopic Dermatitis
Netherton Syndrome
Drug: Placebo (Vehicle)
Drug: BPR277 ointment
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A First-in-human Study to Evaluate Safety and Tolerability of Topical BPR277 in Healthy Volunteers, and Proof of Concept (PoC) Studies to Evaluate the Safety, Tolerability, and Efficacy of Topical BPR277 in Patients With Atopic Dermatitis and Netherton Syndrome

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Part 1: Change in Local Tolerability Score [ Time Frame: Baseline, Week 2 ] [ Designated as safety issue: No ]
  • Part 1: Number of Participants with Adverse Events as a Measure of Safety [ Time Frame: 2 weeks ] [ Designated as safety issue: Yes ]
    Number of Participants with Adverse Events as assessed by the collection of adverse events and laboratory tests for hematology and blood chemistry.

  • Part 2 and 3: (Patients with Atopic Dermatitis / Netherton syndrome) Change in Total Lesional Signs Score at the treated skin area [ Time Frame: Baseline, Week 4 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Part 2 and 3: (Patients with Atopic Dermatitis / Netherton syndrome) Change for each sign comprising the total lesional signs score at the treated skin area [ Time Frame: Baseline, Week 4 ] [ Designated as safety issue: No ]
  • Part 2 and 3: BPR277 Concentration in Plasma [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • Part 2 and 3: BPR277 Concentration in the Skin [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • Part 2 and 3: BPR277 Urinary Excretion [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • Part 2 and 3A: Change in Transepidermal Water Loss [ Time Frame: Baseline, Week 4 ] [ Designated as safety issue: No ]
  • Part 2 and 3A: Change in Skin Capacitance [ Time Frame: Baseline, Week 4 ] [ Designated as safety issue: No ]

Estimated Enrollment: 85
Study Start Date: May 2011
Estimated Study Completion Date: March 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1: Healthy Volunteers
BPR277 and Placebo (vehicle) applied as per protocol.
Drug: Placebo (Vehicle) Drug: BPR277 ointment
Experimental: Part 2: BPR277
BPR277 applied as per protocol.
Drug: BPR277 ointment
Placebo Comparator: Part 2: Placebo (vehicle)
Placebo (vehicle) applied as per protocol
Drug: Placebo (Vehicle)
Experimental: Part 3: Cohort A
BPR277 and Placebo (vehicle) applied as per protocol twice daily.
Drug: Placebo (Vehicle) Drug: BPR277 ointment
Experimental: Part 3: Cohort AA
BPR277 and Placebo (vehicle) applied as per protocol twice daily.
Drug: Placebo (Vehicle) Drug: BPR277 ointment
Experimental: Part 3: Cohort AB
BPR277 and Placebo (vehicle) applied as per protocol once daily.
Drug: Placebo (Vehicle) Drug: BPR277 ointment

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Part 1 Healthy volunteers

  • Healthy male and female subjects of non childbearing potential, 18 to 65 years of age inclusive and in good health

Part 2 (Patients with atopic dermatitis):

  • Male and female subjects, 18 to 65 years of age inclusive and having passed screening examinations
  • Presence of atopic dermatitis confirmed by Itchy skin condition in the past 12 months (must have) Plus three or more of the following:

    1. History of involvement of the skin creases
    2. Personal history of asthma or hay fever
    3. History of generally dry skin in the past year
    4. Onset before age of 2 years
    5. Visible flexural dermatitis
  • Diagnosis of at least moderate atopic dermatitis by the IGA and a minimum target area (right or left) situated on the forearm including the antecubital fossa with a corresponding baseline total lesional sign score (TLSS)

Part 3 Cohorts A, AA and AB (Patients with Netherton Syndrome):

  • Patients with Netherton syndrome, male and female subjects, 18 to 65 years of age inclusive and having passed screening examinations
  • Confirmed diagnosis of Netherton syndrome (SPINK5 mutation or LEKTI deficiency in the skin).
  • Minimum total lesional sign score NS (TLSS-NS) of 5-9 for two selected target areas at baseline. The TLSS-NS values need to be similar between the two areas at baseline.

Exclusion Criteria:

Part 1 Healthy volunteers :

  • History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes or history of serious allergic reaction.
  • Use of any prescription drugs, herbal supplements, within four (4) weeks prior to initial dosing, and/or over-the-counter (OTC) medication, dietary supplements (vitamins included) within two (2) weeks prior to initial dosing.

Part 2 (Patients with atopic dermatitis):

  • History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes or history of serious allergic reaction.
  • History of abnormal skin reactivity to UV light. Unusual exposure to UV light in the previous 3 weeks to study start (screening), including tanning and sun beds.
  • Pregnant or nursing (lactating) women.
  • Women of child-bearing potential must use highly effective contraception (as further defined in study protocol)
  • Use of topical prescription treatment for eczema within 1 week prior to initial dosing of topical corticosteroids (TCS).
  • Recent previous treatment with systemic treatment including phototherapy. A washout period will be required for such patients to be eligible to participate in the trial.

Part 3 Cohorts A, AA and AB (Patients with Netherton Syndrome):

  • History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes or history of serious allergic reaction.
  • History of abnormal skin reactivity to UV light. Unusual exposure to UV light in the previous 3 weeks to study start (screening), including tanning and sun beds.
  • Pregnant or nursing (lactating) women.
  • Women of child-bearing potential must use highly effective contraception (as further defined in study protocol)
  • Use of topical prescription treatment within 2 week prior to initial dosing of study drug.
  • Recent previous treatment with systemic treatment. A washout period will be required for such patients to be eligible to participate in the trial.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01428297

Locations
United States, California
Novartis Investigative Site
San Diego, California, United States, 92123
United States, Connecticut
Novartis Investigative Site
New Haven, Connecticut, United States, 06519
United States, Indiana
Novartis Investigative Site
Indianapolis, Indiana, United States, 46256
United States, Kentucky
Novartis Investigative, Site
Louisville, Kentucky, United States, 40202
United States, Missouri
Novartis Investigative Site
Saint Louis, Missouri, United States, 63104
United States, New Jersey
Novartis Investigative Site
Rochelle Park, New Jersey, United States, 07662
United States, North Carolina
Novartis Investigative Site
Highpoint, North Carolina, United States, 27262
United States, North Dakota
Novartis Investigative Site
Fargo, North Dakota, United States, 58104
United States, Texas
Novartis Investigative Site
Austin, Texas, United States, 78759
France
Novartis Investigative Site
Nice, France
Novartis Investigative Site
Paris, France
Germany
Novartis Investigative Site
Frankfurt, Germany
Novartis Investigative Site
Kiel, Germany
Novartis Investigative Site
Munster, Germany
Netherlands
Novartis Investigative Site
Utrecht, Netherlands
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01428297     History of Changes
Other Study ID Numbers: CBPR277X2101, 2011-000917-38
Study First Received: August 19, 2011
Last Updated: November 25, 2013
Health Authority: United States: Food and Drug Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO); Ministry of Health, Welfare and Sport

Keywords provided by Novartis:
Atopic dermatitis
Eczema
Skin Diseases, Eczematous
Netherton syndrome
Skin Diseases, Genetic
BPR277

Additional relevant MeSH terms:
Netherton Syndrome
Dermatitis
Dermatitis, Atopic
Skin Diseases
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases, Eczematous
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Abnormalities, Multiple
Congenital Abnormalities
Ichthyosiform Erythroderma, Congenital
Ichthyosis
Skin Abnormalities
Infant, Newborn, Diseases
Keratosis

ClinicalTrials.gov processed this record on April 22, 2014