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

Healthy Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03689829
• Other study ID #: MOR106-CL-102
• Secondary ID: 2018-000357-44
• Status: Terminated
• Phase: Phase 1
• Start date: August 13, 2018
• Est. completion date: March 2, 2020

Study information

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

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 44
• Est. completion date: March 2, 2020
• Est. primary completion date: March 2, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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-? (IFN-?), 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.

Related Conditions & MeSH terms

• Atopic Dermatitis
• Dermatitis
• Dermatitis, Atopic
• Eczema
• Healthy

Intervention

Drug:
• MOR106
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 interleukin-17C (IL-17C).
• Placebo
Corresponding placebo s.c. injections.

Locations

Country	Name	City	State
Germany	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
Spain	Hospital General Universitario de Alicante	Alicante
Spain	Hospital Ramon y Cajal	Madrid
Spain	Hospital Universitario Virgen Macarena	Sevilla
Spain	Hospital General Universitario de Valencia	Valencia
Ukraine	Arensia	Kapitanivka
United Kingdom	MEU	Manchester
United Kingdom	MeDiNova North London	Northwood
United Kingdom	MeDiNova East London	Romford
United Kingdom	MeDiNova South London	Sidcup

Sponsors (1)

Lead Sponsor	Collaborator
Galapagos NV

Countries where clinical trial is conducted

Germany,  Spain,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From study drug administration until Day 50 postdose or early discontinuation (ED) visit
Primary	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.	To evaluate the safety and tolerability of multiple doses of MOR106 administered s.c.	From study drug administration until Day 197 postdose or early discontinuation (ED) visit
Primary	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.	To evaluate the safety and tolerability of multiple doses of MOR106 administered s.c.	From study drug administration until Day 155 postdose or early discontinuation (ED) visit
Primary	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.	Between Day 1 study period and Day 50 postdose or early discontinuation (ED) visit
Primary	Area under the serum concentration-time curve from time zero to infinity (AUC0-inf) Part 1.	To characterize the pharmacokinetics (PK) of MOR106.	Between Day 1 study period and Day 50 postdose or early discontinuation (ED) visit
Primary	Terminal elimination half-life (t1/2) Part 1.	To characterize the PK of MOR106.	Between Day 1 study period and Day 50 postdose or early discontinuation (ED) visit
Primary	Maximum observed plasma concentration (Cmax) Part 1.	To characterize the PK of MOR106.	Between Day 1 study period and Day 50 postdose or early discontinuation (ED) visit
Secondary	Occurrence of anti-drug antibodies (ADA) Part 1.	To monitor the occurrence of ADA after single administrations of MOR106.	From baseline through Day 50 postdose or early discontinuation (ED) visit
Secondary	Occurrence of anti-drug antibodies (ADA) Part 2.	To monitor the occurrence of ADA after multiple administrations of MOR106.	From baseline through Day 197 postdose or early discontinuation (ED) visit
Secondary	Occurrence of anti-drug antibodies (ADA) Part 3.	To monitor the occurrence of ADA after multiple administrations of MOR106.	From baseline through Day 155 postdose or early discontinuation (ED) visit
Secondary	MOR106 serum concentrations after multiple s.c. administrations Part 2.	Steady-state will be assessed using MOR106 serum concentrations.	Between Day 1 study period and Day 197 postdose or early discontinuation (ED) visit
Secondary	MOR106 serum concentrations after multiple s.c. administrations Part 3.	Steady-state will be assessed using MOR106 serum concentrations.	Between Day 1 study period and Day 155 postdose or early discontinuation (ED) visit
Secondary	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.	From baseline to Day 85
Secondary	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.	From baseline to Day 85
Secondary	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.	From baseline to Day 85
Secondary	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.	From baseline to Day 85
Secondary	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.	From baseline to Day 85
Secondary	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.	From baseline to Day 85
Secondary	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.	From baseline to Day 85
Secondary	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.	From baseline to Day 85
Secondary	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.	at Day 85 visit
Secondary	Proportion of subjects who achieve an Investigators' Global Assessment (IGA) score of 0 or 1 Part 3.	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.	at Day 85 visit
Secondary	Proportion of subjects who achieve an Investigators' Global Assessment (IGA) score reduction of =2 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.	at Day 85 visit
Secondary	Proportion of subjects who achieve an Investigators' Global Assessment (IGA) score reduction of =2 Part 3.	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.	at Day 85 visit
Secondary	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.	From baseline to Day 85
Secondary	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.	From baseline to Day 85
Secondary	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.	From baseline to Day 85
Secondary	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.	From baseline to Day 85
Secondary	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'.	From screening until Day 197 or early discontinuation (ED) visit twice daily
Secondary	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'.	From screening until Day 155 or early discontinuation (ED) visit twice daily