Clinical trial NCT03689829: A Study to Test Safety, Tolerability, and the Way the Body Absorbs, Distributes, and Gets Rid of a Study Drug Called MOR106, in Healthy Subjects and in Patients With Moderate to Severe Atopic Dermatitis
Official title: A Parallel-design Phase 1 Study to Assess Safety, Tolerability and Pharmacokinetics/Exposure Following Different Single Dose Levels of MOR106 (Administered Subcutaneously or Intravenously) in Healthy Male Subjects (Randomized, Open-label), and in Subjects With Moderate to Severe Atopic Dermatitis (Randomized, Placebo-controlled, Double-blind, Repeated Subcutaneous Dosing Over 12 Weeks)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Healthy
Atopic Dermatitis
Lead sponsor: Galapagos NV
Sponsor class: INDUSTRY
First posted: 2018-09-28
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The clinical study consists of three parts:

* Part 1 with healthy volunteers.
* Part 2 and Part 3 including subjects with moderate to severe atopic dermatitis (a skin disease).

For Part 1 the main goal of the study is to compare the safety, tolerability, and exposure of administration of the test drug via an injection in a skin layer just under the surface (subcutaneous), to administration of the test drug into the vein (intravenous).

For Part 2 and Part 3 the main goal of the study is to assess the safety and tolerability of administration of the test drug via an injection in a skin layer just under the surface (subcutaneous) during 12 weeks of treatment.


Eligibility criteria: Inclusion Criteria:

Part 1:

* Male between 18-50 years of age (extremes included), on the day of signing the informed consent form (ICF).
* Subjects between 65-88 kg (extremes included) with a body mass index (BMI) between 18-30 kg/m², inclusive.
* Judged to be in good health based upon the results of a medical history, physical examination, vital signs, 12-lead electrocardiogram (ECG), and screening laboratory profile prior to the initial investigation medicinal product (IMP) administration.

Part 2 and Part 3:

* Male or female between 18-65 years of age (extremes included), on the day of signing ICF.
* A BMI between 18-30 kg/m², inclusive.
* Diagnosis of AD for at least one year since first diagnosis as per Hanifin and Rajka Criteria.
* EASI ≥ 12 at screening and ≥ 16 at the baseline visit (Day 1 predose)
* ≥ 10% BSA of AD involvement at screening.
* IGA score ≥ 3 (on 0-4 IGA scale).
* Willingness to use an additive free, basic, bland emollient twice daily for at least seven days before the baseline visit and throughout the study.
* Subject is a candidate for systemic therapy and is not responding adequately or has a contraindication to topical corticosteroids (TCS) and / or topical calcineurin inhibitors (TCI), per investigator's judgment.

Exclusion Criteria:

Part 1, Part 2 and Part 3:

* Known hypersensitivity to IMP ingredients as determined by the investigator (such as, but not limited to, anaphylaxis requiring hospitalization).
* Prior treatment with MOR106.
* 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 three months prior to initial IMP 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.
* History of, or current immunosuppressive condition.

In addition for Part 2 and 3:

* Active chronic or acute skin infection requiring treatment with systemic (oral, sc or iv) antibiotics, antivirals or antifungals within 4 weeks of baseline, or clinical signs of infective eczema within 1 week before baseline (Day 1 pre-dose).
* Having used any of the following treatments:

  i) Exposure to a biologic therapy for AD. ii) Immunosuppressive/ immunomodulating drugs (e.g. systemic corticosteroids, cyclosporine, mycophenolate-mofetil, interferon-γ (IFN-γ), azathioprine, methotrexate, etc.) within 4 weeks of baseline. iii) Phototherapy (ultraviolet (UVB) or Psoralen Ultraviolet A \[PUVA\]) for AD within four weeks of baseline. iv) Treatment with TCS or TCI within two weeks before the baseline visit. v) Treatment with biologics (for non-AD indications) within five half-lives (if known) or 12 weeks prior to baseline visit, whichever is longer. vi) Regular use (more than two visits per week) of a tanning booth/parlor within four weeks of the screening visit.

Primary outcomes:
measure: The number of incidents of Treatment-emergent adverse events (TEAEs), adverse events of special interest (AESIs), serious adverse events (SAEs) and discontinuations due to Adverse Events (AEs) Part 1.
timeFrame: From study drug administration until Day 50 postdose or early discontinuation (ED) visit
measure: The number of incidents of Treatment-emergent adverse events (TEAEs), adverse events of special interest (AESIs), serious adverse events (SAEs) and discontinuations due to Adverse Events (AEs) Part 2.
timeFrame: From study drug administration until Day 197 postdose or early discontinuation (ED) visit
measure: The number of incidents of Treatment-emergent adverse events (TEAEs), adverse events of special interest (AESIs), serious adverse events (SAEs) and discontinuations due to Adverse Events (AEs) Part 3.
timeFrame: From study drug administration until Day 155 postdose or early discontinuation (ED) visit
measure: AUC ratio between s.c. and i.v. dosing (area under the plasma concentration-time curve) Part 1.
timeFrame: Between Day 1 study period and Day 50 postdose or early discontinuation (ED) visit
measure: Area under the serum concentration-time curve from time zero to infinity (AUC0-inf) Part 1.
timeFrame: Between Day 1 study period and Day 50 postdose or early discontinuation (ED) visit
measure: Terminal elimination half-life (t1/2) Part 1.
timeFrame: Between Day 1 study period and Day 50 postdose or early discontinuation (ED) visit
measure: Maximum observed plasma concentration (Cmax) Part 1.
timeFrame: Between Day 1 study period and Day 50 postdose or early discontinuation (ED) visit
Secondary outcomes:
measure: Occurrence of anti-drug antibodies (ADA) Part 1.
timeFrame: From baseline through Day 50 postdose or early discontinuation (ED) visit
measure: Occurrence of anti-drug antibodies (ADA) Part 2.
timeFrame: From baseline through Day 197 postdose or early discontinuation (ED) visit
measure: Occurrence of anti-drug antibodies (ADA) Part 3.
timeFrame: From baseline through Day 155 postdose or early discontinuation (ED) visit
measure: MOR106 serum concentrations after multiple s.c. administrations Part 2.
timeFrame: Between Day 1 study period and Day 197 postdose or early discontinuation (ED) visit
measure: MOR106 serum concentrations after multiple s.c. administrations Part 3.
timeFrame: Between Day 1 study period and Day 155 postdose or early discontinuation (ED) visit
measure: Percent change in Eczema Area and Severity Index (EASI) Part 2.
timeFrame: From baseline to Day 85
measure: Percent change in Eczema Area and Severity Index (EASI) Part 3.
timeFrame: From baseline to Day 85
measure: Proportion of subjects who achieve ≥50% overall improvement in Eczema Area and Severity Index (EASI) score Part 2.
timeFrame: From baseline to Day 85
measure: Proportion of subjects who achieve ≥50% overall improvement in Eczema Area and Severity Index (EASI) score Part 3.
timeFrame: From baseline to Day 85
measure: Time to first response of Eczema Area and Severity Index (EASI) improvement with 50% Part 2.
timeFrame: From baseline to Day 85
measure: Time to first response of Eczema Area and Severity Index (EASI) improvement with 50% Part 3.
timeFrame: From baseline to Day 85
measure: Proportion of subjects who achieve ≥75% and ≥90% improvement in Eczema Area and Severity Index (EASI) Part 2.
timeFrame: From baseline to Day 85
measure: Proportion of subjects who achieve ≥75% and ≥90% improvement in Eczema Area and Severity Index (EASI) Part 3.
timeFrame: From baseline to Day 85
measure: Proportion of subjects who achieve an Investigators' Global Assessment (IGA) score of 0 or 1 Part 2.
timeFrame: at Day 85 visit
measure: Proportion of subjects who achieve an Investigators' Global Assessment (IGA) score of 0 or 1 Part 3.
timeFrame: at Day 85 visit
measure: Proportion of subjects who achieve an Investigators' Global Assessment (IGA) score reduction of ≥2 Part 2.
timeFrame: at Day 85 visit
measure: Proportion of subjects who achieve an Investigators' Global Assessment (IGA) score reduction of ≥2 Part 3.
timeFrame: at Day 85 visit
measure: Percent change in Scoring Atopic Dermatitis (SCORAD) score Part 2.
timeFrame: From baseline to Day 85
measure: Percent change in Scoring Atopic Dermatitis (SCORAD) score Part 3.
timeFrame: From baseline to Day 85
measure: Absolute and percent change in body surface area (BSA), Patient Oriented Eczema Measure (POEM) score Part 2.
timeFrame: From baseline to Day 85
measure: Absolute and percent change in body surface area (BSA), Patient Oriented Eczema Measure (POEM) score Part 3.
timeFrame: From baseline to Day 85
measure: Weekly change from baseline in Pruritus Numeric Rating Scale (NRS) Part 2.
timeFrame: From screening until Day 197 or early discontinuation (ED) visit twice daily
measure: Weekly change from baseline in Pruritus Numeric Rating Scale (NRS) Part 3.
timeFrame: From screening until Day 155 or early discontinuation (ED) visit twice daily
Other outcomes:
Locations:
city: Augsburg
country: Germany
facility: Klinikum Augsburg Süd
city: Dessau
country: Germany
facility: Municipal Hospital Dessau
city: Dresden
country: Germany
facility: University Hospital Carl Gustav Carus
city: Erlangen
country: Germany
facility: University Hospital Erlangen, Department of Dermatology
city: Magdeburg
country: Germany
facility: Medical Faculty University Clinic Magdeburg, University dermatology clinic
city: Recklinghausen
country: Germany
facility: Vest Clinic, Department of Dermatology and Allergy
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia
city: Kapitanivka
country: Ukraine
facility: Arensia
city: Manchester
country: United Kingdom
facility: MEU
city: Northwood
country: United Kingdom
facility: MeDiNova North London
city: Romford
country: United Kingdom
facility: MeDiNova East London
city: Sidcup
country: United Kingdom
facility: MeDiNova South London
Study officials:
affiliation: Galapagos NV
name: Helen Timmis, MB CHB
role: STUDY_DIRECTOR
References: