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

• Sponsor: Novartis Pharmaceuticals
• Information provided by: Novartis

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Healthy Volunteers; Atopic Dermatitis; Netherton Syndrome	Drug: BPR277 ointment (controlled application); Drug: Placebo (Vehicle); Drug: BPR277 ointment; Drug: BPR277	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Double (Participant, 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
• Study Start Date: May 2011
• Actual Primary Completion Date: February 2014
• Actual Study Completion Date: February 2014

Arms and Interventions

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: BPR277; Drug: Placebo (Vehicle)

Outcome Measures

Primary Outcome Measures :

1. 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. [ Time Frame: 2-4 weeks ]
2. Part 2 and 3: Patients with Atopic Dermatitis / Netherton syndrome: Change in Total Lesional Signs Score at the treated skin area [ Time Frame: 4 weeks ]

Secondary Outcome Measures :

1. 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: 4 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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 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.

Contacts and Locations

Locations

United States, Connecticut

Novartis Investigative Site

New Haven, Connecticut, United States, 06519

United States, Missouri

Novartis Investigative Site

St. Louis, Missouri, United States, 63104

United States, North Dakota

Novartis Investigative Site

Fargo, North Dakota, United States, 58104

Netherlands

Novartis Investigative Site

Utrecht, the Netherlands, Netherlands, 3508 GA

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

• Responsible Party: Clinical Disclosure Office, Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01428297 History of Changes
• Other Study ID Numbers: CBPR277X2101; 2011-000917-38
• First Posted: September 2, 2011
• Last Update Posted: February 4, 2015
• Last Verified: February 2015

Keywords provided by Novartis:

Atopic dermatitis; Eczema; Skin Diseases, Eczematous; Netherton syndrome; Skin Diseases, Genetic; BPR277

Additional relevant MeSH terms:

Syndrome; Dermatitis; Dermatitis, Atopic; Eczema; Netherton Syndrome; Disease; Pathologic Processes; 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