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

NCT03689829 | Terminated Phase 1

• 2 other identifiers: MOR106-CL-1022018-000357-44
• Study Type: interventional
• Target: 44
• Locations: 4 countries
• Sites: 15

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.

Conditions

Healthy; Atopic Dermatitis

Outcome Measures

Primary Outcomes (7)

• 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

• 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

• 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

• 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

• 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

• 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

• 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 Outcomes (23)

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

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

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

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

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

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

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

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

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

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

Study Arms (8)

MOR106 Single Dose A, i.v. infusion, Part 1

EXPERIMENTAL

A single dose of MOR106 will be administered by i.v. infusion.

Drug: MOR106

MOR106 Single Dose B, s.c. injection, Part 1

EXPERIMENTAL

A single dose of MOR106 will be administered by s.c. injection.

Drug: MOR106

MOR106 Single Dose C, s.c. injection, Part 1

EXPERIMENTAL

A single dose of MOR106 will be administered by s.c. injection.

Drug: MOR106

MOR106 Single Dose D, s.c. injection, Part 1

EXPERIMENTAL

A single dose of MOR106 will be administered by s.c. injection.

Drug: MOR106

MOR106 Repeated Doses E, s.c. injection, Part 2

EXPERIMENTAL

Repeated doses of MOR106 will be administered by s.c. injection with a loading dose on the first day of administration.

Drug: MOR106

Placebo s.c.injection, Part 2

PLACEBO COMPARATOR

Corresponding Placebo will be administered by s.c. injection.

Drug: Placebo

MOR106 Repeated Doses F, s.c. injection, Part 3

EXPERIMENTAL

Repeated doses of MOR106 will be administered by s.c. injection with a loading dose on the first day of administration.

Drug: MOR106

Placebo s.c.injection, Part 3

PLACEBO COMPARATOR

Corresponding Placebo will be administered by s.c. injection.

Drug: Placebo

Interventions

MOR106 DRUG

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).

MOR106 Repeated Doses E, s.c. injection, Part 2; MOR106 Repeated Doses F, s.c. injection, Part 3; MOR106 Single Dose A, i.v. infusion, Part 1; MOR106 Single Dose B, s.c. injection, Part 1; MOR106 Single Dose C, s.c. injection, Part 1; MOR106 Single Dose D, s.c. injection, Part 1

Placebo DRUG

Corresponding placebo s.c. injections.

Placebo s.c.injection, Part 2; Placebo s.c.injection, Part 3

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Galapagos NV: lead

Study Sites (15)

Klinikum Augsburg Süd

Augsburg, 86179, Germany

Location

Municipal Hospital Dessau

Dessau, 06847, Germany

Location

University Hospital Carl Gustav Carus

Dresden, 1307, Germany

Location

University Hospital Erlangen, Department of Dermatology

Erlangen, 91054, Germany

Location

Medical Faculty University Clinic Magdeburg, University dermatology clinic

Magdeburg, 39120, Germany

Location

Vest Clinic, Department of Dermatology and Allergy

Recklinghausen, 45657, Germany

Location

Hospital General Universitario de Alicante

Alicante, 03010, Spain

Location

Hospital Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

Location

Hospital General Universitario de Valencia

Valencia, 46014, Spain

Location

Arensia

Kapitanivka, 08112, Ukraine

Location

MEU

Manchester, United Kingdom

Location

MeDiNova North London

Northwood, HA6 2RN, United Kingdom

Location

MeDiNova East London

Romford, RM1 3PJ, United Kingdom

Location

MeDiNova South London

Sidcup, DA14 6LT, United Kingdom

Location

MeSH Terms

Conditions

Dermatitis, Atopic

Condition Hierarchy (Ancestors)

Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Helen Timmis, MB CHB

  Galapagos NV

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Part 1 - randomized open label. Part 2 and Part 3 - randomized double blind.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2018
• First Posted: September 28, 2018
• Study Start: August 13, 2018
• Primary Completion: March 2, 2020
• Study Completion: March 2, 2020
• Last Updated: March 18, 2020

Record last verified: 2020-03

Locations

ES (4); UA (1); GB (4); DE (6)