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

NCT01732510 | Terminated Phase 1 Results

• 2 other identifiers: 8226-0032012-005560-95
• Study Type: interventional
• Target: 65
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a 3-part study to assess the safety, tolerability, efficacy, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of MK-8226 in participants with moderate to severe atopic dermatitis. Part 1 (multiple rising dose study) objectives were to find the maximum tolerated dose (MTD) of MK-8226 and to assess safety and PK. Part 2 objectives were to determine safety, PK, and preliminary efficacy. Part 3 objectives were to further define safety and PK, and explore MK-8226 PK/PD to model the optimal dose range for future studies. The study was terminated early due to business reasons on 08 May 2014; final results from an analysis for Part 1 (efficacy, PK, safety, immunogenicity) and Part 2 (safety, immunogenicity) are summarized.

Conditions

Atopic Dermatitis

Outcome Measures

Primary Outcomes (3)

• Number of Participants Who Experienced at Least One Adverse Event

  An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.

  Up to 32 Weeks

• Number of Participants Who Discontinued Study Drug Due to an Adverse Event

  An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.

  Up to 12 Weeks

• Change From Baseline in the Eczema Area and Severity Index (EASI) for Study Part 1

  Reduction from baseline in EASI at Week 12 (interim analysis data). The EASI assesses intensity of four lesion characteristics (erythema, infiltration/population, excoriation, lichenification) each rated on a scale of 0 (absent) to 3 (severe) across four regions (head, trunk, upper and lower extremities). Affected areas in each region are assessed as percentage of body surface (head \[10%\], trunk \[30%\], upper extremities \[20%\], and lower extremities \[40%\]). The total score is a sum of each region score and can range from 0 (absent disease) to 72 (severe disease).

  Baseline, Week 12

Secondary Outcomes (16)

• Plasma Chemokine (C-C Motif) Ligand 17 (CCL17) Level in Study Part 2

  Baseline, 48 Hours, Week 2, Week 4, Week 12, Week 16

• Plasma Chemokine (C-C Motif) Ligand 22 (CCL22) Level in Study Part 2

  Baseline, 48 Hours, Week 2, Week 4, Week 12, Week 16

• Area Under the Concentration-time Curve of MK-8226 From Time 0 to Tau (AUC0-tau) Following Multiple Intravenous Dose Administration

  Days 1, 3, 5, 9, 14, 70, 72, 74, 84

• AUC From Time 0 to Last Measurement (AUC0-last) of MK-8226 Following Multiple Intravenous Dose Administration

  Days 70, 72, 74, 84, 98, 112, 140, 168, 196, 224

• Maximum Serum Concentration (Cmax) of MK-8226 Following Multiple Dose Intravenous Administration

  Days 1, 3, 5, 9, 14, 70, 72, 74, 84

Other Outcomes (1)

• Change From Baseline in the Participant's Global Impression of Disease Status in Study Part 2

  Baseline, Week 4, Week 12, Week 24

Study Arms (7)

Part 1: MK-8226 0.3 mg/kg

EXPERIMENTAL

MK-8226 administered intravenously (IV) at a weight-based dose every 2 weeks for a period of 12 weeks.

Drug: MK-8226

Part 1: MK-8226 1 mg/kg

EXPERIMENTAL

MK-8226 administered IV at a weight-based dose every 2 weeks for a period of 12 weeks.

Drug: MK-8226

Part 1: MK-8226 3 mg/kg

EXPERIMENTAL

MK-8226 administered IV at a weight-based dose every 2 weeks for a period of 12 weeks.

Drug: MK-8226

Part 1: MK-8226 10 mg/kg

EXPERIMENTAL

MK-8226 administered IV at a weight-based dose every 2 weeks for a period of 12 weeks.

Drug: MK-8226

Part 1: Placebo (pooled)

PLACEBO COMPARATOR

Dose-matched placebo administered IV every 2 weeks for a period of 12 weeks.

Drug: Placebo

Part 2: MK-8226 3 mg/kg

EXPERIMENTAL

MK-8226 administered IV at a weight-based dose every 2 weeks for a period of 12 weeks.

Drug: MK-8226

Part 2: Placebo

PLACEBO COMPARATOR

Placebo administered IV every 2 weeks for a period of 12 weeks.

Drug: Placebo

Interventions

MK-8226 DRUG

MK-8226 administered IV at a weight-based dose every 2 weeks for 12 weeks.

Part 1: MK-8226 0.3 mg/kg; Part 1: MK-8226 1 mg/kg; Part 1: MK-8226 10 mg/kg; Part 1: MK-8226 3 mg/kg; Part 2: MK-8226 3 mg/kg

Placebo DRUG

Placebo administered IV every 2 weeks for a period of 12 weeks.

Part 1: Placebo (pooled); Part 2: Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 tuberculosis (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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

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

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2012
• First Posted: November 22, 2012
• Study Start: December 21, 2012
• Primary Completion: October 20, 2014
• Study Completion: October 20, 2014
• Last Updated: March 15, 2019
• Results First Posted: June 9, 2016

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will share