A Study Evaluating the Safety and Efficacy of Topical BPR277 for the Treatment of Atopic Dermatitis and Netherton Syndrome (3)

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

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).

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers; Atopic Dermatitis; Netherton Syndrome
• Intervention / Treatment: Drug: BPR277 ointment (controlled application); Drug: Placebo (Vehicle); Drug: BPR277 ointment; Drug: BPR277

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • The Netherlands
    • Utrecht, The Netherlands, Netherlands, 3508 GA
      • Novartis Investigative Site
• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Novartis Investigative Site
  • Missouri
    • Saint Louis, Missouri, United States, 63104
      • Novartis Investigative Site
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 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 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A and B, BPR277 and Placebo (vehicle)	Drug: BPR277 ointment (controlled application); Drug: Placebo (Vehicle)
Experimental: Part 2 BPR277	Drug: BPR277 ointment
Placebo Comparator: Part 2 Placebo (vehicle)	Drug: Placebo (Vehicle)
Experimental: Part 3 BPR277 and Placebo (vehicle)	Drug: Placebo (Vehicle); Drug: BPR277

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Systemic and local tolerability of BPR277 ointment, as measured by change in local tolerability score, number of adverse events and clinically significant changes in standard hematology, blood chemistry.	2-4 weeks
Part 2 and 3: Patients with Atopic Dermatitis / Netherton syndrome: Change in Total Lesional Signs Score at the treated skin area	4 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
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	4 weeks

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Results for CBPR277X2101 can be found on the Novartis Clinical Trial Results Website

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): February 1, 2014
• Study Completion (Actual): February 1, 2014

Study Registration Dates

• First Submitted: August 19, 2011
• First Submitted That Met QC Criteria: September 1, 2011
• First Posted (Estimate): September 2, 2011

Study Record Updates

• Last Update Posted (Actual): December 8, 2020
• Last Update Submitted That Met QC Criteria: December 6, 2020
• Last Verified: February 1, 2015

More Information

Terms related to this study

• Keywords: Atopic dermatitis; Eczema; Netherton syndrome; Skin Diseases, Genetic; Skin Diseases, Eczematous; BPR277
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Disease; Congenital Abnormalities; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Skin Abnormalities; Abnormalities, Multiple; Keratosis; Ichthyosiform Erythroderma, Congenital; Ichthyosis; Syndrome; Dermatitis; Eczema; Dermatitis, Atopic; Netherton Syndrome
• Other Study ID Numbers: CBPR277X2101; 2011-000917-38