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

Phase 1TerminatedNCT03689829

Lakefront Biotherapeutics NV44 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Healthy Atopic Dermatitis

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (15)

Klinikum Augsburg Süd

Augsburg, Germany

Municipal Hospital Dessau

Dessau, Germany

University Hospital Carl Gustav Carus

Dresden, Germany

University Hospital Erlangen, Department of Dermatology

Erlangen, Germany

Medical Faculty University Clinic Magdeburg, University dermatology clinic

Magdeburg, Germany

Vest Clinic, Department of Dermatology and Allergy

Recklinghausen, Germany

Hospital General Universitario de Alicante

Alicante, Spain

Hospital Ramon y Cajal

Madrid, Spain

Hospital Universitario Virgen Macarena

Seville, Spain

Hospital General Universitario de Valencia

Valencia, Spain

...and 5 more locations

Outcomes

Primary Outcomes

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.

To evaluate the safety and tolerability of single doses of MOR106 administered s.c. in comparison to i.v.

Time frame: From study drug administration until Day 50 postdose or early discontinuation (ED) visit

To evaluate the safety and tolerability of multiple doses of MOR106 administered s.c.

Time frame: From study drug administration until Day 197 postdose or early discontinuation (ED) visit

To evaluate the safety and tolerability of multiple doses of MOR106 administered s.c.

Time frame: From study drug administration until Day 155 postdose or early discontinuation (ED) visit

AUC ratio between s.c. and i.v. dosing (area under the plasma concentration-time curve) Part 1.

To determine the relative bioavailability following sc route of administration.

Time frame: Between Day 1 study period and Day 50 postdose or early discontinuation (ED) visit

Area under the serum concentration-time curve from time zero to infinity (AUC0-inf) Part 1.

To characterize the pharmacokinetics (PK) of MOR106.

Time frame: Between Day 1 study period and Day 50 postdose or early discontinuation (ED) visit

Terminal elimination half-life (t1/2) Part 1.

To characterize the PK of MOR106.

Time frame: Between Day 1 study period and Day 50 postdose or early discontinuation (ED) visit

Maximum observed plasma concentration (Cmax) Part 1.

To characterize the PK of MOR106.

Time frame: Between Day 1 study period and Day 50 postdose or early discontinuation (ED) visit

Secondary Outcomes

Occurrence of anti-drug antibodies (ADA) Part 1.

To monitor the occurrence of ADA after single administrations of MOR106.

Time frame: From baseline through Day 50 postdose or early discontinuation (ED) visit

Occurrence of anti-drug antibodies (ADA) Part 2.

To monitor the occurrence of ADA after multiple administrations of MOR106.

Time frame: From baseline through Day 197 postdose or early discontinuation (ED) visit

Occurrence of anti-drug antibodies (ADA) Part 3.

To monitor the occurrence of ADA after multiple administrations of MOR106.

Time frame: From baseline through Day 155 postdose or early discontinuation (ED) visit

MOR106 serum concentrations after multiple s.c. administrations Part 2.

Steady-state will be assessed using MOR106 serum concentrations.

Time frame: Between Day 1 study period and Day 197 postdose or early discontinuation (ED) visit

MOR106 serum concentrations after multiple s.c. administrations Part 3.

Steady-state will be assessed using MOR106 serum concentrations.

Time frame: Between Day 1 study period and Day 155 postdose or early discontinuation (ED) visit

Percent change in Eczema Area and Severity Index (EASI) Part 2.

To assess the efficacy of MOR106 by use of EASI score. The EASI score ranges are between 0 (no eczema) and 72. Higher values represent a worse outcome.

Time frame: From baseline to Day 85

Percent change in Eczema Area and Severity Index (EASI) Part 3.

To assess the efficacy of MOR106 by use of EASI score. The EASI score ranges are between 0 (no eczema) and 72. Higher values represent a worse outcome.

Time frame: From baseline to Day 85

Proportion of subjects who achieve ≥50% overall improvement in Eczema Area and Severity Index (EASI) score Part 2.

To assess the efficacy of MOR106 by use of EASI score. The EASI score ranges are between 0 (no eczema) and 72. Higher values represent a worse outcome.

Time frame: From baseline to Day 85

Proportion of subjects who achieve ≥50% overall improvement in Eczema Area and Severity Index (EASI) score Part 3.

To assess the efficacy of MOR106 by use of EASI score. The EASI score ranges are between 0 (no eczema) and 72. Higher values represent a worse outcome.

Time frame: From baseline to Day 85

Time to first response of Eczema Area and Severity Index (EASI) improvement with 50% Part 2.

To assess the efficacy of MOR106 by use of EASI score. The EASI score ranges are between 0 (no eczema) and 72. Higher values represent a worse outcome.

Time frame: From baseline to Day 85

Time to first response of Eczema Area and Severity Index (EASI) improvement with 50% Part 3.

To assess the efficacy of MOR106 by use of EASI score. The EASI score ranges are between 0 (no eczema) and 72. Higher values represent a worse outcome.

Time frame: From baseline to Day 85

Proportion of subjects who achieve ≥75% and ≥90% improvement in Eczema Area and Severity Index (EASI) Part 2.

To assess the efficacy of MOR106 by use of EASI score,The EASI score ranges are between 0 (no eczema) and 72. Higher values represent a worse outcome.

Time frame: From baseline to Day 85

Proportion of subjects who achieve ≥75% and ≥90% improvement in Eczema Area and Severity Index (EASI) Part 3.

To assess the efficacy of MOR106 by use of EASI score,The EASI score ranges are between 0 (no eczema) and 72. Higher values represent a worse outcome.

Time frame: From baseline to Day 85

Proportion of subjects who achieve an Investigators' Global Assessment (IGA) score of 0 or 1 Part 2.

To assess the efficacy of MOR106 by use of IGA score, an assessment scale to determine severity of AD and clinical response to treatment based on a 5-point scale ranging from 0 (clear) to 4 (severe) score. Higher values represent a worse outcome.

Time frame: at Day 85 visit

Proportion of subjects who achieve an Investigators' Global Assessment (IGA) score of 0 or 1 Part 3.

Time frame: at Day 85 visit

Proportion of subjects who achieve an Investigators' Global Assessment (IGA) score reduction of ≥2 Part 2.

Time frame: at Day 85 visit

Proportion of subjects who achieve an Investigators' Global Assessment (IGA) score reduction of ≥2 Part 3.

Time frame: at Day 85 visit

Percent change in Scoring Atopic Dermatitis (SCORAD) score Part 2.

To assess the efficacy of MOR106 by use of SCORAD.The SCORAD evaluates the extent of atopic dermatitis and ranges between 0 and 103. Higher values represent a worse outcome.

Time frame: From baseline to Day 85

Percent change in Scoring Atopic Dermatitis (SCORAD) score Part 3.

To assess the efficacy of MOR106 by use of SCORAD.The SCORAD evaluates the extent of atopic dermatitis and ranges between 0 and 103. Higher values represent a worse outcome.

Time frame: From baseline to Day 85

Absolute and percent change in body surface area (BSA), Patient Oriented Eczema Measure (POEM) score Part 2.

To assess the efficacy of MOR106 by use of POEM. The POEM is calculated by summing the score of each question resulting in a maximum score of 28 and a minimum score of 0.

Time frame: From baseline to Day 85

Absolute and percent change in body surface area (BSA), Patient Oriented Eczema Measure (POEM) score Part 3.

To assess the efficacy of MOR106 by use of POEM. The POEM is calculated by summing the score of each question resulting in a maximum score of 28 and a minimum score of 0.

Time frame: From baseline to Day 85

Weekly change from baseline in Pruritus Numeric Rating Scale (NRS) Part 2.

To assess the efficacy of MOR106 by NRS. An 11-point (0 - 10) scale will be used to assess itch (pruritus). 0 being 'no itch' and 10 being the 'worst itch imaginable'.

Time frame: From screening until Day 197 or early discontinuation (ED) visit twice daily

Weekly change from baseline in Pruritus Numeric Rating Scale (NRS) Part 3.

To assess the efficacy of MOR106 by NRS. An 11-point (0 - 10) scale will be used to assess itch (pruritus). 0 being 'no itch' and 10 being the 'worst itch imaginable'.

Time frame: From screening until Day 155 or early discontinuation (ED) visit twice daily