Part 2: Atopic Dermatitis (AD) Part 3: Netherton Syndrome (NS) MedDRA version: 14.1 Level: LLT Classification code 10003639 Term: Atopic dermatitis System Organ Class: 100000004858 MedDRA version: 14.1 Level: PT Classification code 10062909 Term: Netherton's syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Code: BPR277
Pharmaceutical Form: Ointment
INN or Proposed INN: not available
Current Sponsor code: BPR277
Other descriptive name: BPR277
Concentration unit: mg/g milligram(s)/gram
Concentrati
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects eligible for inclusion in this study have to fulfill all of the following criteria. Other protocol-defined inclusion criteria apply in addition to those listed hereafter: Part 1: 1.Written informed consent must be obtained before any assessment is performed. 2.Healthy male and female subjects of non childbearing potential, 18 to 65 years of age inclusive and in good health 3.Subjects must weigh at least 50kg to participate in the study, and must have a body mass index (BMI) within the range of 18-35kg/m2. 4.Study subjects must be able to communicate well with the investigator, to understand and comply with the requirements of the study. Part 2: 1.Written informed consent must be obtained before any assessment is performed. 2.Male and female subjects, 18 to 65 years of age inclusive and having passed screening examinations 3.Presence of atopic dermatitis confirmed by Itchy skin condition in the past 12 months (must have) Plus three or more of the following: •History of involvement of the skin creases •Personal history of asthma or hay fever •History of generally dry skin in the past year •Onset before age of 2 years •Visible flexural dermatitis 4.Diagnosis of at least moderate atopic dermatitis by the IGA of the to-be-treated area at screening; and a 250 cm2 to-be-treated area of skin containing at least ~50% AD affected skin. The 250 cm2 treatment area is to be ideally situated on the forearm including the antecubital fossa with a total lesional sign score (TLSS) of at least 10 at screening. Alternative locations for the treatment area are detailed in the protocol. Areas that must not be chosen are: hands and feet, head and neck, back, armpits and the groin. 5.A total lesional sign score (TLSS) at baseline of 2-4 within the study treatment area. 6.Subjects must weigh at least 50 kg to participate in the study, and must have a body mass index (BMI) within the range of 18-42 kg/m2. 7.Study subjects must be able to communicate well with the investigator, to understand and comply with the requirements of the study Part 3 Cohort 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. Other protocol-defined inclusion/exclusion criteria may apply. Refer to protocol for details. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 85 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Subjects fulfilling any of the following criteria are not eligible for inclusion in this study. Other protocol-defined exclusion criteria apply in addition to those listed hereafter: Part 1: 1.Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer. 2.History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes or history of serious allergic reaction. 3.A history of clinically significant ECG abnormalities, or ECG abnormalities at Screening or Baseline. 4.History of malignancy of any organ system, treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases. 5.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. 6.Total WBC count which falls outside the range of 4500–11,000/µl, or platelets <100,000/µl, or hemoglobin levels below 12.0 g/dl at screening. 7.Donation or loss of 400 ml or more of blood within eight (8) weeks prior to initial dosing, or longer if required by local regulation. 8.Recent and/or recurrent history of autonomic dysfunction 9.Liver disease or liver injury as indicated by abnormal liver function tests 10.History or presence of impaired renal function 11.Evidence of urinary obstruction or difficulty in voiding at screening. 12.History of hypertrophic scarring. 13.History of immunodeficiency diseases. Part 2: 1.Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer. 2.History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes or history of serious allergic reaction. 3.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. 4.Pregnant or nursing (lactating) women. 5.Women of child-bearing potential must use highly effective contraception (as further defined in study protocol) during the study and the duration of the study. 6.Use of topical prescription treatment for eczema (topical corticosteroids, calcineurin inhibitors, antibiotics, etc...) on the selected study treatment area within 1 week prior to initial dosing of topical corticosteroids (TCS). 7.Recent previous treatment with phototherapy, biological therapy, immunosuppressive agents such as cyclosporine, mycophenolate, pimecrolimus or tacrolimus. A washout period will be required for such patients to be eligible to participate in the trial. 8.Donation or loss of 400 ml or more of blood within eight (8) weeks prior to initial dosing, or longer if required by local regulation. 9.History of malignancy of any organ system, treated or untreated, within the past 5 years. 10.History of clinically significant ECG abnormalities or Screening/Baseline ECG abnormalities 11.Inability or unwillingness to undergo multiple venipunctures 12.History of hypertrophic scarring. Part 3 Cohorts A, AA & 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 (
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •Demonstrate tolerability (systemic and local) of repeated twice daily topical applications of BPR277 ointment in adult subjects, and in patients with AD and NS (all parts) •In Part 2, evaluate whether BPR277 1% ointment maintains a treatment effect, induced by topical corticosteroids, by assessing that TLSS increase is at most half of that of its vehicle in AD patients. •In Part 3A, assess the potential of BPR277 1% ointment b.i.d. to improve clinically severity of lesional skin (TLSS-NS) in the majority of NS patients at end of treatment versus baseline of = 2 points. •In Part 3 (cohorts A, AA & AB), assess dose regimen relationship on clinical severity of lesional skin (TLSS-NS) in NS patients after treatment with two regimens of BPR277 (1% ointment, applied either b.i.d. or q.d.);Secondary Objective: •Evaluate systemic steady state pharmacokinetics in human after topical administration of BPR277 ointment. •Determine BPR277 concentrations in the skin and the urinary excretion of BPR277 after repeated topical administration of BPR277 ointment in adult HV subjects and patients with AD and NS (for NS only in Part 3A). •Assess the ability of repeated topical applications of BPR277 to restore the skin barrier function in AD and NS patients as demonstrated by the change in Transepidermal Water Loss (TEWL) and skin capacitance (Part 2/3A);Primary end point(s): Maximum skin tolerability score Part 2, Total Lesional Signs Score Part 3, Clinical response using NS (TLSS-NS) score Part 3 Cohort AA & AB, assess the potential of BPR277 (1% ointment, applied either b.i.d. or q.d.) to improve the clinical severity of lesional skin (TLSS-NS) in NS patients.;Timepoint(s) of evaluation of this end point: Maximum skin tolerability score: Part 1: Day(D)1, D2-D14, and D22 Part 2: D-7, D-4, D-2, D1, D8, D15, D22, D29 & D43 Part 3: D-7, D1, D8, D15, D22, D29 & D43 Part 2, Total Lesional Signs Score: D-7, D-4, D-2, D1, D8, D15, D22, D29 and D43 Part 3, Clinical respo | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy/Pharmacodynamics: Part 2 Scores for each of the six clinical signs comprising the total lesional sign score; Lesional itch VAS; Investigator Global Assessment and Patient’s Global Severity Assessment Part 3 Total lesional sign score for NS; Scores for each of the four clinical signs comprising the total lesional sign score for NS; Lesional itch VAS; Investigator Global Assessment and Patient’s Global Severity Assessment Safety (All parts): Vital signs, AEs, concomitant medications/significant non-drug therapies; ECG evaluations and standard clinical laboratory evaluations;Timepoint(s) of evaluation of this end point: Efficacy/Pharmacodynamics: Part 2-completed Part 3 Cohort A-completed Part 3 Cohort AA & AB Total Lesional Sign Score for NS; D-7, D1, D8, D15, D29, D43. Lesional itch VAS & Investigator Global Assessment; D-7, D1, D8, D15, D29, D43. Patient’s global severity assessment: D-7, D1, D8, D15, D29, D43. Vital signs (VS); D-7, D1, D15, D29, D43. AEs, Concomitant medications/ significant non-drug therapies; D-7 [except concomitant medications], D1, D8, D15, D29, D43. ECGs; D-7, D1, D29, D43. Standard laboratory evaluations: D-7, D1, D15, D29, D43. | — |
Countries
France, Germany, Netherlands, United States
Contacts
Public ContactMedizinischer Infoservice
Novartis Pharma GmbH
Outcome results
None listed