A Study to Assess Efficacy, Safety, Tolerability and Pharmacokinetics (PK)/Pharmacodynamics (PD) of MOR106 in Subjects With Moderate to Severe Atopic Dermatitis

Atopic Dermatitis Clinical Trial

— IGUANA  

Official title:

A Phase II, Randomized, Double-blind, Placebo-controlled Repeated-dose Study to Evaluate the Efficacy, Safety, Tolerability,and PK/PD of Intravenously Administered MOR106 in Adult Subjects With Moderate to Severe Atopic Dermatitis

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03568071
• Other study ID #: MOR106-CL-201
• Secondary ID: 2017-001142-10
• Status: Terminated
• Phase: Phase 2
• Start date: April 26, 2018
• Est. completion date: March 3, 2020

Study information

• Verified date: March 2020
• Source: Galapagos NV
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase II, randomized, double-blind, placebo-controlled multicenter study of repeated doses of MOR106 administered as IV infusion. MOR106, is an antibody which is being developed as a treatment for diseases such as psoriasis and atopic dermatitis. An antibody is a protein that is made by the body in a defense reaction against viruses and bacteria or other small particles. In this case, MOR106 will act against IL-17C interleukin by binding to it. This way it could be possible to act against these diseases.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 207
• Est. completion date: March 3, 2020
• Est. primary completion date: March 3, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Male or female between 18-65 years of age (extremes included), on the day of signing informed consent form (ICF).

• Able and willing to give voluntary written informed consent and meet all of the inclusion criteria and none of the exclusion criteria before being enrolled in the study. The subjects must sign the informed consent form prior to any study-related procedures and agree to the schedule of assessments.

• A body mass index (BMI) between =18 and =30 kg/m².

• Diagnosis of chronic atopic dermatitis with at least 1 year since first diagnosis, as per the Hanifin and Rajka Criteria, fulfilling the following criteria:

1. EASI =12 at screening and =16 at baseline (Day 1 pre-dose).

2. Investigator's Global Assessment (IGA) score =3 (on the 0 to 4 IGA scale, in which 3 is moderate and 4 is severe) at screening and at baseline.

3. Greater than or equal to 10% body surface area (BSA) of atopic dermatitis involvement at screening.

4. Willingness to continue stable use of an additive free, basic, bland emollient twice daily for at least 7 days before baseline and throughout the study.

5. Subject is a candidate for systemic therapy and has a history of inadequate response or has a contraindication to topical corticosteroids and/or topical calcineurin inhibitors before screening visit, as per investigator's opinion.

• Willing to adhere to the following contraceptive restrictions:

1. Female subjects of childbearing potential must have a negative serum pregnancy test at screening, and a negative urine pregnancy test at baseline.

2. Female subjects of childbearing potential must use a highly effective method of contraception from 28 days prior to the first dose of study drug, during the study, and for at least 24 weeks after the last dose of study drug.

3. Non-vasectomized male subjects with a female partner of childbearing potential must agree to a highly effective form of contraception during the study, and for at least 24 weeks after last dose of study drug.

4. All male subjects must agree to use a condom from the first dose of Investigational Medicinal Product (IMP), during the study and for at least 24 weeks after the last dose of IMP.

Exclusion Criteria:

• Known hypersensitivity to study drug ingredients or history of any significant allergic reaction to any drug as determined by the investigator, such as anaphylaxis requiring hospitalization.

• Prior treatment with MOR106.

• Positive serology for hepatitis B (positive hepatitis B surface [HBs] antigen and/or positive hepatitis core antibody [HBc]), or hepatitis C virus (HCV) antibody or any history of hepatitis from any cause with the exception of hepatitis A. Subjects who are immune to hepatitis B because of vaccination can be included.

• History of or current immunosuppressive condition (e.g., human immunodeficiency virus [HIV] infection), including history of invasive opportunistic infections (e.g., TB, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis), despite infection resolution or unusually frequent, recurrent, or prolonged infections, per investigator judgment.

• Subjects with a history of Varicella zoster virus who experienced any episode or recurrence of Herpes Zoster infection within 1 year of screening or = one episode or Herpes Zoster within 1 year of screening must be excluded. (A history of Herpes simplex types 1 and 2 and vaginal candidiasis are permitted.)

• Pregnant or breast feeding female or subject is intending to become pregnant or breastfeed.

• Any concurrent illness, condition, disability, or clinically significant abnormality (including laboratory tests, = New York Heart Association Classification (NYHA) III/IV) or clinically significant illness in the 3 months prior to initial study drug administration that, in the investigator's opinion, represents a safety risk for the subject's participation in the study, may affect the interpretation of clinical safety or efficacy data, or may prevent the subject from safely completing the assessments required by the protocol.

• Any of the following laboratory findings:

1. White blood cell count <3.0 x 109 cells/L

2. Neutrophil count <1.5 x 109 cells/L

3. Platelet count <100 x 109 cells/L

4. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 x upper limit of normal (ULN)

• History of malignancy within the past 5 years prior to screening with the exception of non-metastatic basal cell carcinoma or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or of the breast, prostate cancer T1a or T1b using the TNM (tumour, nodes, metastasis) clinical staging system.

• Clinically significant abnormalities at the discretion of the investigator detected on vital signs or physical examination (other than atopic dermatitis) at screening or baseline (Day 1 pre-dose).

• History of eczema herpeticum in the last 12 months prior to screening.

• Subjects who have had an attenuated vaccination within 4 weeks of baseline or are expected to have one during the course of the study.

• Participation in another experimental therapy study within 5 times the half-life (if known) or 12 weeks (if not known) of the experimental therapy, prior to baseline, or current enrollment in any other interventional study.

• Having used any of the following treatments:

1. Exposure to a biologic therapy for atopic dermatitis

2. Immunosuppressive/ immunomodulating drugs (e.g., systemic corticosteroids, cyclosporine, mycophenolate-mofetil, interferon-gamma, azathioprine, methotrexate) within 4 weeks of baseline

3. Phototherapy (ultraviolet [UV] B or psoralen and ultraviolet A [PUVA]) for atopic dermatitis within 4 weeks of baseline

4. Treatment with topical corticosteroids or topical calcineurin inhibitors within 2 weeks of baseline

5. Treatment with biologics (for non atopic dermatitis indications within 5 half-lives (if known) or 12 weeks prior to baseline (if unknown)

6. Regular use (more than 2 visits per week) of a tanning booth/parlour within 4 weeks of screening

• Active chronic or acute infection requiring treatment with systemic (oral, SC or IV) antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals, within 4 weeks of baseline, or clinical signs of infective eczema within 1 week before baseline. Note: subjects may be rescreened after infection resolves.

• Investigator, research assistant, pharmacist, study coordinator, or other staff or relative thereof, who is directly involved in the conduct of the study.

• Not able to manage the electronic diary (e-diary) as per assessment of the investigator.

Related Conditions & MeSH terms

• Atopic Dermatitis
• Dermatitis
• Dermatitis, Atopic
• Eczema

Intervention

Drug:
• MOR 106
The active pharmaceutical drug substance of MOR106 is a human immunoglobulin gamma-1 (IgG1) monoclonal antibody that binds with a high apparent affinity to human IL-17C.
• Placebo
A sodium chloride infusion container with IV solution without addition of MOR106 drug product will be used as placebo in the proposed clinical study.

Locations

Country	Name	City	State
Germany	Fachklinik Bad Bentheim, Department of Dermatology	Bad Bentheim
Germany	Charite, Universitätsmedizin Berlin, Centrum 12, Klinik für Dermatologie, Venerologie und Allergologie	Berlin
Germany	Korsearch. Studienzentrum	Berlin
Germany	Hautarztpraxis im Jahrhunderthaus	Bochum
Germany	Hauttumorzentrum Ruhr- Universität Bochum	Bochum
Germany	RuhrDerm - Studienzentrum der Gemeinschaftspraxis für Dermatologie, Venerologie, Allergologie, Phlebologie	Bochum
Germany	Elbe Klinikum Buxtehude	Buxtehude
Germany	Universitätsklinikum Frankfurt, Klinik für Dermatologie	Frankfurt
Germany	SCIderm GmbH (a company of TFS group)	Hamburg
Germany	Universitätsklinikum Heidelberg, Hautklinik	Heidelberg
Germany	Institut für Entzündungsmedizin	Lubeck
Germany	Clinical research center (CRC), Department of Dermatology	Mainz
Germany	Klinik und Poliklinik der Dermatologie und Allergologie der Universität München	München
Germany	Technical University Munich, Department of Dermatology	Munich
Germany	University Hospital of Muenster, Dpt. of Dermatology	Münster
Germany	Haut- und Lasercentrum Potsdam	Potsdam
Hungary	Budai Irgalmasrendi Kórház (St. John Hospital)	Budapest
Hungary	Semmelweis Egyetem Borgyógyászati Klinika	Budapest
Hungary	Bács-Kiskun Megyei Kórház Borgyógyászati Osztály	Kecskemét
Hungary	Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Oktatókórház	Miskolc
Hungary	Szegedi Egyetem Borgyógyászati és Allergológiai Klinika	Szeged
Poland	CERMED	Bialystok
Poland	Antoni Jurasz Universiti Hospital Nº1	Bydgoszcz
Poland	NZOZ Centrum Medyczne KERmed	Bydgoszcz
Poland	A-DERM-SERWIS NZOZ , Przychodnia Specjalistyczna	Czestochowa
Poland	Centrum Badan Klinicznych PI-House	Gdansk
Poland	Gyncentrum	Katowice
Poland	Centrum Medyczne ALL-MED	Kraków
Poland	Diamond Clinic	Kraków
Poland	Medical Center Dietla 19	Kraków
Poland	NZOZ Centrum Medyczne proMimed	Kraków
Poland	ETG Lódz	Lódz
Poland	KLIMED Marek Klimkiewicz	Lomza
Poland	Prywatny Gabinet Lekarski Urszula Chyrchel-Paszkiewicz	Lublin
Poland	Samodzielny Publiczny Szpital Kliniczny nr 1 Katedra i Klinika Dermatologii, Wenerologii i Dermatologii Dzieciecej	Lublin
Poland	Labderm sc Beata Bergler-Czop Barbara Sido-Bergler	Ossy
Poland	Dermedic Jacek Zdybski	Ostrowiec Swietokrzyski
Poland	Ostrowieckie Centrum Medyczne	Ostrowiec Swietokrzyski
Poland	KLIMED Marek Klimkiewicz	Piotrków Trybunalski
Poland	Centrum Badan Klinicznych S.C.	Poznan
Poland	Centrum Medyczne Grunwald	Poznan
Poland	Clinical Research Center Sp. z o.o. Medic-R Spólka Komandytowa	Poznan
Poland	ETG Skierniewice	Skierniewice
Poland	Centrum Medyczne AMED	Warsaw
Poland	ETG Warszawa	Warsaw
Poland	Clinical Research Group	Warszawa
Poland	4HEALTH	Wroclaw
Poland	Dobrostan	Wroclaw
Slovakia	University Hospital Bratislava	Bratislava
United Kingdom	Whipps Cross Hospital	Leytonstone
United Kingdom	Plymouth Hospitals NHS Trust	Plymouth
United Kingdom	Sheffield Teaching Hospitals NHS Foundation Trust, Royal Hallamshire Hospital	Sheffield
United Kingdom	The Royal London Hospital	Whitechapel

Sponsors (1)

Lead Sponsor	Collaborator
Galapagos NV

Countries where clinical trial is conducted

Germany,  Hungary,  Poland,  Slovakia,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent change in Eczema Area and Severity Index (EASI) score.	To assess the clinical efficacy of repeated IV doses of MOR106 as assessed by percentage change from baseline in EASI score at Day 85 visit. The EASI score ranges are between 0 (no eczema) and 72. Higher values represent a worse outcome.	From baseline to Day 85
Secondary	Proportion of subjects who achieve =50% overall improvement in Eczema Area and Severity Index (EASI) score.	To assess the clinical efficacy of repeated IV doses of MOR106. The EASI score ranges are between 0 (no eczema) and 72. Higher values represent a worse outcome.	From baseline to Day 85
Secondary	Proportion of subjects who achieve =50% overall improvement in Eczema Area and Severity Index (EASI) score.	To assess the clinical efficacy of repeated IV doses of MOR106. The EASI score ranges are between 0 (no eczema) and 72. Higher values represent a worse outcome.	At Day 1
Secondary	Proportion of subjects who achieve =50% overall improvement in Eczema Area and Severity Index (EASI) score.	To assess the clinical efficacy of repeated IV doses of MOR106. The EASI score ranges are between 0 (no eczema) and 72. Higher values represent a worse outcome.	At Day 15
Secondary	Proportion of subjects who achieve =50% overall improvement in Eczema Area and Severity Index (EASI) score.	To assess the clinical efficacy of repeated IV doses of MOR106. The EASI score ranges are between 0 (no eczema) and 72. Higher values represent a worse outcome.	At Day 29
Secondary	Proportion of subjects who achieve =50% overall improvement in Eczema Area and Severity Index (EASI) score.	To assess the clinical efficacy of repeated IV doses of MOR106. The EASI score ranges are between 0 (no eczema) and 72. Higher values represent a worse outcome.	At Day 43
Secondary	Proportion of subjects who achieve =50% overall improvement in Eczema Area and Severity Index (EASI) score.	To assess the clinical efficacy of repeated IV doses of MOR106. The EASI score ranges are between 0 (no eczema) and 72. Higher values represent a worse outcome.	At Day 57
Secondary	Proportion of subjects who achieve =50% overall improvement in Eczema Area and Severity Index (EASI) score.	To assess the clinical efficacy of repeated IV doses of MOR106. The EASI score ranges are between 0 (no eczema) and 72. Higher values represent a worse outcome.	At Day 71
Secondary	Proportion of subjects who achieve an Investigators' Global Assessment (IGA) score of 0 or 1.	To assess the clinical efficacy of repeated IV doses of MOR106.The IGA is an assessment scale to determine severity of atopic dermatitis and clinical response to treatment based on a 5-point scale ranging from 0 (clear) to 4 (severe).	At Day 85
Secondary	Proportion of subjects who achieve an Investigators' Global Assessment (IGA) score of 0 or 1.	To assess the clinical efficacy of repeated IV doses of MOR106.The IGA is an assessment scale to determine severity of atopic dermatitis and clinical response to treatment based on a 5-point scale ranging from 0 (clear) to 4 (severe).	At Day 1
Secondary	Proportion of subjects who achieve an Investigators' Global Assessment (IGA) score of 0 or 1.	To assess the clinical efficacy of repeated IV doses of MOR106.The IGA is an assessment scale to determine severity of atopic dermatitis and clinical response to treatment based on a 5-point scale ranging from 0 (clear) to 4 (severe).	At Day 15
Secondary	Proportion of subjects who achieve an Investigators' Global Assessment (IGA) score of 0 or 1.	To assess the clinical efficacy of repeated IV doses of MOR106.The IGA is an assessment scale to determine severity of atopic dermatitis and clinical response to treatment based on a 5-point scale ranging from 0 (clear) to 4 (severe).	At Day 29
Secondary	Proportion of subjects who achieve an Investigators' Global Assessment (IGA) score of 0 or 1.	To assess the clinical efficacy of repeated IV doses of MOR106.The IGA is an assessment scale to determine severity of atopic dermatitis and clinical response to treatment based on a 5-point scale ranging from 0 (clear) to 4 (severe).	At Day 43
Secondary	Proportion of subjects who achieve an Investigators' Global Assessment (IGA) score of 0 or 1.	To assess the clinical efficacy of repeated IV doses of MOR106.The IGA is an assessment scale to determine severity of atopic dermatitis and clinical response to treatment based on a 5-point scale ranging from 0 (clear) to 4 (severe).	At Day 57
Secondary	Proportion of subjects who achieve an Investigators' Global Assessment (IGA) score of 0 or 1.	To assess the clinical efficacy of repeated IV doses of MOR106.The IGA is an assessment scale to determine severity of atopic dermatitis and clinical response to treatment based on a 5-point scale ranging from 0 (clear) to 4 (severe).	At Day 71
Secondary	Proportion of subjects who achieve Investigators' Global Assessment (IGA) score reduction of =2.	To assess the clinical efficacy of repeated IV doses of MOR106.The IGA is an assessment scale to determine severity of atopic dermatitis and clinical response to treatment based on a 5-point scale ranging from 0 (clear) to 4 (severe).	At Day 85
Secondary	Proportion of subjects who achieve Investigators' Global Assessment (IGA) score reduction of =2.	To assess the clinical efficacy of repeated IV doses of MOR106.The IGA is an assessment scale to determine severity of atopic dermatitis and clinical response to treatment based on a 5-point scale ranging from 0 (clear) to 4 (severe).	At Day 1
Secondary	Proportion of subjects who achieve Investigators' Global Assessment (IGA) score reduction of =2.	To assess the clinical efficacy of repeated IV doses of MOR106.The IGA is an assessment scale to determine severity of atopic dermatitis and clinical response to treatment based on a 5-point scale ranging from 0 (clear) to 4 (severe).	At Day 15
Secondary	Proportion of subjects who achieve Investigators' Global Assessment (IGA) score reduction of =2.	To assess the clinical efficacy of repeated IV doses of MOR106.The IGA is an assessment scale to determine severity of atopic dermatitis and clinical response to treatment based on a 5-point scale ranging from 0 (clear) to 4 (severe).	At Day 29
Secondary	Proportion of subjects who achieve Investigators' Global Assessment (IGA) score reduction of =2.	To assess the clinical efficacy of repeated IV doses of MOR106.The IGA is an assessment scale to determine severity of atopic dermatitis and clinical response to treatment based on a 5-point scale ranging from 0 (clear) to 4 (severe).	At Day 43
Secondary	Proportion of subjects who achieve Investigators' Global Assessment (IGA) score reduction of =2.	To assess the clinical efficacy of repeated IV doses of MOR106.The IGA is an assessment scale to determine severity of atopic dermatitis and clinical response to treatment based on a 5-point scale ranging from 0 (clear) to 4 (severe).	At Day 57
Secondary	Proportion of subjects who achieve Investigators' Global Assessment (IGA) score reduction of =2.	To assess the clinical efficacy of repeated IV doses of MOR106.The IGA is an assessment scale to determine severity of atopic dermatitis and clinical response to treatment based on a 5-point scale ranging from 0 (clear) to 4 (severe).	At Day 71
Secondary	Percent change in Scoring Atopic Dermatitis (SCORAD) score.	To assess the clinical efficacy of repeated IV doses of MOR106. The SCORAD evaluates the extent of atopic dermatitis and ranges between 0 and 103. Higher values represent a worse outcome.	From baseline to Day 85
Secondary	Percent change in Scoring Atopic Dermatitis (SCORAD) score.	To assess the clinical efficacy of repeated IV doses of MOR106. The SCORAD evaluates the extent of atopic dermatitis and ranges between 0 and 103. Higher values represent a worse outcome.	At Day 1
Secondary	Percent change in Scoring Atopic Dermatitis (SCORAD) score.	To assess the clinical efficacy of repeated IV doses of MOR106. The SCORAD evaluates the extent of atopic dermatitis and ranges between 0 and 103. Higher values represent a worse outcome.	At Day 15
Secondary	Percent change in Scoring Atopic Dermatitis (SCORAD) score.	To assess the clinical efficacy of repeated IV doses of MOR106. The SCORAD evaluates the extent of atopic dermatitis and ranges between 0 and 103. Higher values represent a worse outcome.	At Day 29
Secondary	Percent change in Scoring Atopic Dermatitis (SCORAD) score.	To assess the clinical efficacy of repeated IV doses of MOR106. The SCORAD evaluates the extent of atopic dermatitis and ranges between 0 and 103. Higher values represent a worse outcome.	At Day 43
Secondary	Percent change in Scoring Atopic Dermatitis (SCORAD) score.	To assess the clinical efficacy of repeated IV doses of MOR106. The SCORAD evaluates the extent of atopic dermatitis and ranges between 0 and 103. Higher values represent a worse outcome.	At Day 57
Secondary	Percent change in Scoring Atopic Dermatitis (SCORAD) score.	To assess the clinical efficacy of repeated IV doses of MOR106. The SCORAD evaluates the extent of atopic dermatitis and ranges between 0 and 103. Higher values represent a worse outcome.	At Day 71
Secondary	The number of incidents of Treatment-Emergent Adverse Events (TEAEs), Adverse Event of Special Interest (AESIs), Serious Adverse Events (SAEs), and discontinuations due to Adverse Events (AEs).	To assess the safety and tolerability of repeated IV doses of MOR106.	From screening up to Day 197/early discontinuation (ED) visit
Secondary	Characterization of the MOR106 immunogenetic profile.	To assess the immunogenicity of repeated IV doses of MOR106.	From baseline through Day 197/ED visit
Secondary	MOR106 (AUC0-inf)	To characterize the PK of repeated IV doses of MOR106.	From baseline through Day 197/ED visit