Clinical trial NCT03568071: A Study to Assess Efficacy, Safety, Tolerability and Pharmacokinetics (PK)/Pharmacodynamics (PD) of MOR106 in Subjects With Moderate to Severe Atopic Dermatitis
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Atopic Dermatitis
Lead sponsor: Galapagos NV
Sponsor class: INDUSTRY
First posted: 2018-06-26
Enrollment: 207
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percent change in Eczema Area and Severity Index (EASI) score.
timeFrame: From baseline to Day 85
Secondary outcomes:
measure: Proportion of subjects who achieve ≥50% overall improvement in Eczema Area and Severity Index (EASI) score.
timeFrame: From baseline to Day 85
measure: Proportion of subjects who achieve ≥50% overall improvement in Eczema Area and Severity Index (EASI) score.
timeFrame: At Day 1
measure: Proportion of subjects who achieve ≥50% overall improvement in Eczema Area and Severity Index (EASI) score.
timeFrame: At Day 15
measure: Proportion of subjects who achieve ≥50% overall improvement in Eczema Area and Severity Index (EASI) score.
timeFrame: At Day 29
measure: Proportion of subjects who achieve ≥50% overall improvement in Eczema Area and Severity Index (EASI) score.
timeFrame: At Day 43
measure: Proportion of subjects who achieve ≥50% overall improvement in Eczema Area and Severity Index (EASI) score.
timeFrame: At Day 57
measure: Proportion of subjects who achieve ≥50% overall improvement in Eczema Area and Severity Index (EASI) score.
timeFrame: At Day 71
measure: Proportion of subjects who achieve an Investigators' Global Assessment (IGA) score of 0 or 1.
timeFrame: At Day 85
measure: Proportion of subjects who achieve an Investigators' Global Assessment (IGA) score of 0 or 1.
timeFrame: At Day 1
measure: Proportion of subjects who achieve an Investigators' Global Assessment (IGA) score of 0 or 1.
timeFrame: At Day 15
measure: Proportion of subjects who achieve an Investigators' Global Assessment (IGA) score of 0 or 1.
timeFrame: At Day 29
measure: Proportion of subjects who achieve an Investigators' Global Assessment (IGA) score of 0 or 1.
timeFrame: At Day 43
measure: Proportion of subjects who achieve an Investigators' Global Assessment (IGA) score of 0 or 1.
timeFrame: At Day 57
measure: Proportion of subjects who achieve an Investigators' Global Assessment (IGA) score of 0 or 1.
timeFrame: At Day 71
measure: Proportion of subjects who achieve Investigators' Global Assessment (IGA) score reduction of ≥2.
timeFrame: At Day 85
measure: Proportion of subjects who achieve Investigators' Global Assessment (IGA) score reduction of ≥2.
timeFrame: At Day 1
measure: Proportion of subjects who achieve Investigators' Global Assessment (IGA) score reduction of ≥2.
timeFrame: At Day 15
measure: Proportion of subjects who achieve Investigators' Global Assessment (IGA) score reduction of ≥2.
timeFrame: At Day 29
measure: Proportion of subjects who achieve Investigators' Global Assessment (IGA) score reduction of ≥2.
timeFrame: At Day 43
measure: Proportion of subjects who achieve Investigators' Global Assessment (IGA) score reduction of ≥2.
timeFrame: At Day 57
measure: Proportion of subjects who achieve Investigators' Global Assessment (IGA) score reduction of ≥2.
timeFrame: At Day 71
measure: Percent change in Scoring Atopic Dermatitis (SCORAD) score.
timeFrame: From baseline to Day 85
measure: Percent change in Scoring Atopic Dermatitis (SCORAD) score.
timeFrame: At Day 1
measure: Percent change in Scoring Atopic Dermatitis (SCORAD) score.
timeFrame: At Day 15
measure: Percent change in Scoring Atopic Dermatitis (SCORAD) score.
timeFrame: At Day 29
measure: Percent change in Scoring Atopic Dermatitis (SCORAD) score.
timeFrame: At Day 43
measure: Percent change in Scoring Atopic Dermatitis (SCORAD) score.
timeFrame: At Day 57
measure: Percent change in Scoring Atopic Dermatitis (SCORAD) score.
timeFrame: At Day 71
measure: 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).
timeFrame: From screening up to Day 197/early discontinuation (ED) visit
measure: Characterization of the MOR106 immunogenetic profile.
timeFrame: From baseline through Day 197/ED visit
measure: MOR106 (AUC0-inf)
timeFrame: From baseline through Day 197/ED visit
Other outcomes:
Locations:
city: Bad Bentheim
country: Germany
facility: Fachklinik Bad Bentheim, Department of Dermatology
city: Berlin
country: Germany
facility: Korsearch. Studienzentrum
city: Berlin
country: Germany
facility: Charite, Universitätsmedizin Berlin, Centrum 12, Klinik für Dermatologie, Venerologie und Allergologie
city: Bochum
country: Germany
facility: Hautarztpraxis im Jahrhunderthaus
city: Bochum
country: Germany
facility: Hauttumorzentrum Ruhr- Universität Bochum
city: Bochum
country: Germany
facility: RuhrDerm - Studienzentrum der Gemeinschaftspraxis für Dermatologie, Venerologie, Allergologie, Phlebologie
city: Buxtehude
country: Germany
facility: Elbe Klinikum Buxtehude
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt, Klinik für Dermatologie
city: Hamburg
country: Germany
facility: SCIderm GmbH (a company of TFS group)
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg, Hautklinik
city: Lubeck
country: Germany
facility: Institut für Entzündungsmedizin
city: Mainz
country: Germany
facility: Clinical research center (CRC), Department of Dermatology
city: Munich
country: Germany
facility: Technical University Munich, Department of Dermatology
city: München
country: Germany
facility: Klinik und Poliklinik der Dermatologie und Allergologie der Universität München
city: Münster
country: Germany
facility: University Hospital of Muenster, Dpt. of Dermatology
city: Potsdam
country: Germany
facility: Haut- und Lasercentrum Potsdam
city: Budapest
country: Hungary
facility: Budai Irgalmasrendi Kórház (St. John Hospital)
city: Budapest
country: Hungary
facility: Semmelweis Egyetem Bőrgyógyászati Klinika
city: Kecskemét
country: Hungary
facility: Bács-Kiskun Megyei Kórház Bőrgyógyászati Osztály
city: Miskolc
country: Hungary
facility: Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Oktatókórház
city: Szeged
country: Hungary
facility: Szegedi Egyetem Bőrgyógyászati és Allergológiai Klinika
city: Białystok
country: Poland
facility: CERMED
city: Bydgoszcz
country: Poland
facility: Antoni Jurasz Universiti Hospital Nº1
city: Bydgoszcz
country: Poland
facility: NZOZ Centrum Medyczne KERmed
city: Częstochowa
country: Poland
facility: A-DERM-SERWIS NZOZ , Przychodnia Specjalistyczna
city: Gdańsk
country: Poland
facility: Centrum Badań Klinicznych PI-House
city: Katowice
country: Poland
facility: Gyncentrum
city: Kraków
country: Poland
facility: Centrum Medyczne ALL-MED
city: Kraków
country: Poland
facility: Diamond Clinic
city: Kraków
country: Poland
facility: Medical Center Dietla 19
city: Kraków
country: Poland
facility: NZOZ Centrum Medyczne proMimed
city: Lublin
country: Poland
facility: Prywatny Gabinet Lekarski Urszula Chyrchel-Paszkiewicz
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny nr 1 Katedra i Klinika Dermatologii, Wenerologii i Dermatologii Dziecięcej
city: Ossy
country: Poland
facility: Labderm sc Beata Bergler-Czop Barbara Sido-Bergler
city: Ostrowiec Świętokrzyski
country: Poland
facility: Dermedic Jacek Zdybski
city: Ostrowiec Świętokrzyski
country: Poland
facility: Ostrowieckie Centrum Medyczne
city: Piotrków Trybunalski
country: Poland
facility: KLIMED Marek Klimkiewicz
city: Poznań
country: Poland
facility: Centrum Badan Klinicznych S.C.
city: Poznań
country: Poland
facility: Centrum Medyczne Grunwald
city: Poznań
country: Poland
facility: Clinical Research Center Sp. z o.o. Medic-R Spółka Komandytowa
city: Skierniewice
country: Poland
facility: ETG Skierniewice
city: Warsaw
country: Poland
facility: Centrum Medyczne AMED
city: Warsaw
country: Poland
facility: ETG Warszawa
city: Warszawa
country: Poland
facility: Clinical Research Group
city: Wrocław
country: Poland
facility: 4HEALTH
city: Wrocław
country: Poland
facility: Dobrostan
city: Łomża
country: Poland
facility: KLIMED Marek Klimkiewicz
city: Łódź
country: Poland
facility: ETG Łódź
city: Bratislava
country: Slovakia
facility: University Hospital Bratislava
city: Leytonstone
country: United Kingdom
facility: Whipps Cross Hospital
city: Plymouth
country: United Kingdom
facility: Plymouth Hospitals NHS Trust
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust, Royal Hallamshire Hospital
city: Whitechapel
country: United Kingdom
facility: The Royal London Hospital
Study officials:
affiliation: Galapagos NV
name: Helen Timmis, MBChB MICR
role: STUDY_DIRECTOR
References: