A Study of Intravenous MK-8226 in Participants With Moderate-to-Severe Atopic Dermatitis (MK-8226-003 AM2)

This study is currently recruiting participants.
Verified March 2014 by Merck Sharp & Dohme Corp.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01732510
First received: November 19, 2012
Last updated: March 20, 2014
Last verified: March 2014
  Purpose

This is a 3-part study to assess the safety, tolerability, efficacy, pharmacokinetics, pharmacodynamics, and immunogenicity of MK-8226 in participants with moderate to severe atopic dermatitis. Part 1 will be done to find the maximum tolerated dose (MTD) of MK-8226 and to assess safety and pharmacokinetics. Part 2 will evaluate safety, pharmacokinetics, and preliminary efficacy. Part 3, if done, will further define safety and pharmacokinetics, and will explore MK-8226 pharmacokinetic/pharmacodynamics to model the optimal dose range for future studies if Part 1 does not supply sufficient information to do this.


Condition Intervention Phase
Atopic Dermatitis
Drug: MK-8226
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase Ib Randomized, Double-Blinded, Placebo-Controlled Multiple Rising Dose Clinical Trial to Evaluate the Safety, Efficacy, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Intravenous MK-8226 in Patients With Moderate to Severe Atopic Dermatitis

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Number of Participants Experiencing at Least One Adverse Event (AE) [ Time Frame: Up to 32 Weeks ] [ Designated as safety issue: Yes ]
  • Number of Participants Discontinuing Study Treatment Due to AEs [ Time Frame: Up to 12 Weeks ] [ Designated as safety issue: Yes ]
  • Mean Change From Baseline in the Eczema Area and Severity Index (EASI) for Study Part 2 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Mean Change From Baseline in Chemokine (C-C motif) Ligand 17 (CCL17) in Study Part 2 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
  • Mean Area Under the Curve From Time Zero to Tau (AUC0-tau) of MK-8226 Following Multiple Intravenous Dose Administration [ Time Frame: Predose on Day 1 Through Postdose on Day 224 ] [ Designated as safety issue: No ]
  • Mean AUC From Time Zero to Last Measurement (AUC0-last) of MK-8226 Following Multiple Intravenous Dose Administration [ Time Frame: Predose on Day 1 Through Postdose on Day 224 ] [ Designated as safety issue: No ]
  • Mean Time to Maximum Serum Concentration (Cmax) of MK-8226 Following Multiple Dose Intravenous Administration [ Time Frame: Predose on Day 1 Through Postdose on Day 224 ] [ Designated as safety issue: No ]
  • Mean Clearance (CL) of MK-8226 Following Multiple Dose Intravenous Administration [ Time Frame: Predose on Day 1 Through Postdose on Day 224 ] [ Designated as safety issue: No ]
  • Mean Volume of Distribution (Vd) of MK-8226 Following Multiple Intravenous Administration [ Time Frame: Predose on Day 1 Through Postdose on Day 224 ] [ Designated as safety issue: No ]
  • Mean Terminal Half Life (T1/2) of MK-8226 Following Multiple Dose Intravenous Administration [ Time Frame: Predose on Day 1 Through Postdose on Day 224 ] [ Designated as safety issue: No ]
  • Mean Change From Baseline in the Eczema Area and Severity Index (EASI) for Study Part 2 [ Time Frame: Baseline, Week 4, Week 8, Week 24 ] [ Designated as safety issue: No ]
  • Proportion of Participants With a Investigator Global Assessment (IGA) Score of Clear or Almost Clear in Study Part 2 [ Time Frame: Baseline, Week 4, Week 8, Week 12, Week 24 ] [ Designated as safety issue: No ]
  • Mean Plasma Chemokine (C-C motif) Ligand 22 (CCL22) Level in Study Part 2 [ Time Frame: 48 Hours, Week 4, Week 12, Week 16 ] [ Designated as safety issue: No ]
  • Mean Change From Baseline in the Scoring Atopic Dermatitis Scale (SCORAD) in Study Part 2 [ Time Frame: Baseline, Week 4, Week 12, Week 24 ] [ Designated as safety issue: No ]
  • Mean Change From Baseline in Participant Pruritis in Study Part 2 [ Time Frame: Baseline, Week 4, Week 12, Week 24 ] [ Designated as safety issue: No ]
  • Mean Change From Baseline in Participant Sleep Disturbance in Study Part 2 [ Time Frame: Baseline, Week 4, Week 12, Week 24 ] [ Designated as safety issue: No ]
  • Number of Participants Requiring As-Needed Oral Antihistamines as Rescue Medication in Study Part 2 [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: No ]
  • Mean Change from Baseline in the Participant's Global Impression of Disease Status in Study Part 2 [ Time Frame: Baseline, Week 4, Week 12, Week 24 ] [ Designated as safety issue: No ]
  • Proportion of Participants With >=50% Improvement in EASI Score [ Time Frame: Baseline, Week 12, Week 24 ] [ Designated as safety issue: No ]
  • Number of Participants Positive for Anti-Drug Antibody Formation [ Time Frame: Baseline to Week 32 ] [ Designated as safety issue: No ]

Estimated Enrollment: 170
Study Start Date: December 2012
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Low Dose MK-8226
MK-8226 administered intravenously (IV) at a weight-based dose every 2 weeks for a period of 12 weeks.
Drug: MK-8226
MK-8226 administered IV at a weight-based dose every 2 weeks for 12 weeks.
Experimental: Mid-Low Dose MK-8226
MK-8226 administered IV at a weight-based dose every 2 weeks for a period of 12 weeks.
Drug: MK-8226
MK-8226 administered IV at a weight-based dose every 2 weeks for 12 weeks.
Experimental: Mid-High Dose MK-8226
MK-8226 administered IV at a weight-based dose every 2 weeks for a period of 12 weeks.
Drug: MK-8226
MK-8226 administered IV at a weight-based dose every 2 weeks for 12 weeks.
Experimental: High Dose MK-8226
MK-8226 administered IV at a weight-based dose every 2 weeks for a period of 12 weeks.
Drug: MK-8226
MK-8226 administered IV at a weight-based dose every 2 weeks for 12 weeks.
Placebo Comparator: Placebo
Placebo administered IV every 2 weeks for a period of 12 weeks.
Drug: Placebo
Placebo administered intravenously every 2 weeks for a period of 12 weeks.

Detailed Description:

Part 1 of the study is a multiple rising dose assessment of the safety, tolerability, and pharmacokinetics of MK-8226 for a period of 12 weeks followed by a 20-week off-treatment follow-up period.

Part 2 of the study is an assessment of the safety, tolerability, and efficacy of MK-8226 for 12 weeks followed by a 20-week off-treatment follow-up period.

An interim futility analysis will be performed when approximately 40% of the participants that have been treated with study drug have completed the active treatment portion of the study (Week 12) while additional patients will continue to be enrolled into Part 2 of the study. If the interim results support study continuation, additional participants may be enrolled in Part 3 of the study.

In Part 3 of the study, participants will be treated with MK-8226 for a period of 12 weeks followed by a 20-week off-treatment follow-up period to evaluate pharmacokinetic and pharmacokinetic correlations to assist with modeling the dose range planned for further studies.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Body weight >=40 kg
  • Clinical diagnosis of atopic dermatitis for at least 6 months prior
  • Candidate for systemic or phototherapy (i.e., failed topical treatment)
  • Moderate-to-severe disease as defined by Body Surface Area (BSA) ≥10%, EASI ≥12, and IGA ≥3
  • No clinically significant abnormality on electrocardiogram
  • No history of active or latent TB and no signs or symptoms suggestive of TB
  • No history of active or latent TB and no signs or symptoms suggestive of TB
  • History of inadequate response to a stable (≥ 1 month) regimen of topical corticosteroids or calcineurin inhibitors within 3 months before the screening visit

Exclusion Criteria:

  • Concurrent significant skin disease
  • Any significant organ dysfunction within 6 months prior
  • History of clinically significant heart disease
  • History of neoplastic disease
  • Positive for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)
  • Infection requiring oral antibiotics within 2 weeks prior
  • Receipt of a live virus vaccine within 4 weeks prior
  • Inability to refrain from topical or systemic therapy during course of the study
  • Had major surgery or donated or lost >=1 unit of blood within 4 weeks prior
  • Participation in another study within 4 weeks prior
  • Current or regular user of illicit drugs or a history of drug or alcohol abuse within 1 year prior
  • Pregnant, breast-feeding, or anticipated to conceive during the course of the study
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01732510

Contacts
Contact: Toll Free Number 1-888-577-8839

Locations
United States, California
Call for Information (Investigational Site 0028) Recruiting
Costa Mesa, California, United States, 92626
United States, Colorado
Call for Information (Investigational Site 0010) Recruiting
Denver, Colorado, United States, 80206
United States, Illinois
Call for Information (Investigational Site 0003) Recruiting
Chicago, Illinois, United States, 60611
United States, New York
Call for Information (Investigational Site 0002) Recruiting
New York, New York, United States, 10029
United States, Oregon
Call for Information (Investigational Site 0009) Recruiting
Portland, Oregon, United States, 97239
United States, Texas
Call for Information (Investigational Site 0001) Recruiting
Dallas, Texas, United States, 75246
Austria
MSD ýterreich GmbH Recruiting
Vienna, Austria
Contact: Karl Boegl    43 126044130      
Canada, Quebec
Merck Canada Recruiting
Kirkland, Quebec, Canada, H9H 3L1
Contact: Medical Information Centre / Centre de l'information medicale de Merck Canada    514-428-8600 / 1-800-567-2594      
Denmark
Merck Sharp & Dohme Recruiting
Glostrup, Denmark
Contact: Gert Andersen    45 44824475      
Finland
MSD Finland Oy Recruiting
Espoo, Finland
Contact: Kaisa Elomaa    358 20 7570300      
Germany
Merck Sharp & Dohme GmbH Recruiting
Haar, Germany
Contact: German Medical Information Center    49 800 673 673 673      
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01732510     History of Changes
Other Study ID Numbers: 8226-003
Study First Received: November 19, 2012
Last Updated: March 20, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Dermatitis
Dermatitis, Atopic
Skin Diseases
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases, Eczematous
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases

ClinicalTrials.gov processed this record on April 16, 2014