Last reviewed · How we verify

NCT01732510

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

Terminated Phase 1 Results posted Last updated 15 March 2019
What this trial tests

Phase 1 trial testing MK-8226 in Atopic Dermatitis in 65 participants. Terminated before completion.

Timeline
21 December 2012
Primary endpoint
20 October 2014
20 October 2014

Quick facts

Lead sponsorMerck Sharp & Dohme LLC
PhasePhase 1
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment65
Start date21 December 2012
Primary completion20 October 2014
Estimated completion20 October 2014

Drugs / interventions tested

Conditions studied

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

18 and older, any sex, with Atopic Dermatitis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants Who Experienced at Least One Adverse Event Primary · Up to 32 Weeks

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 sign

GroupValue95% CI
Part 1: MK-8226 0.3 mg/kg8
Part 1: MK-8226 1 mg/kg6
Part 1: MK-8226 3 mg/kg6
Part 1: MK-8226 10 mg/kg7
Part 1: Placebo (Pooled)7
Part 2: MK-8226 3 mg/kg10
Part 2: Placebo7
Number of Participants Who Discontinued Study Drug Due to an Adverse Event Primary · Up to 12 Weeks

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

GroupValue95% CI
Part 1: MK-8226 0.3 mg/kg0
Part 1: MK-8226 1 mg/kg1
Part 1: MK-8226 3 mg/kg1
Part 1: MK-8226 10 mg/kg0
Part 1: Placebo (Pooled)0
Part 2: MK-8226 3 mg/kg0
Part 2: Placebo1
Change From Baseline in the Eczema Area and Severity Index (EASI) for Study Part 1 Primary · Baseline, Week 12

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).

GroupValue95% CI
Part 1: MK-8226 0.3 mg/kg-5.77± 6.17
Part 1: MK-8226 1 mg/kg-8.40± 9.39
Part 1: MK-8226 3 mg/kg-10.20± 7.23
Part 1: MK-8226 10 mg/kg-7.78± 8.35
Part 1: Placebo (Pooled)-0.38± 6.37
Area Under the Concentration-time Curve of MK-8226 From Time 0 to Tau (AUC0-tau) Following Multiple Intravenous Dose Administration Secondary · Days 1, 3, 5, 9, 14, 70, 72, 74, 84

AUC(0-tau) defined as AUC from time zero to tau where tau is the dosing interval (312 hours) was determined for the first and last periods of MK-8226 dosing. MK-8226 was administered on Days 1, 14, 28, 42, 56, and 70. Blood concentrations of MK-8226 were determined on Days 1 (incl. predose), 3, 5, 9, 14 (incl. predose), 70 (incl. predose), 72, 74, 84. The placebo group is not included; this endpoint evaluated only the MK-8226 groups. No analysis was performed for Part 2 non-safety secondary endpoints after the Part 1 primary endpoint (Change from BL in EASI) did not demonstrate adequate effect

Week 1 (n=9,7,8,10)
GroupValue95% CI
Part 1: MK-8226 0.3 mg/kg1000± 18.2
Part 1: MK-8226 1 mg/kg3300± 29.3
Part 1: MK-8226 3 mg/kg9300± 19.1
Part 1: MK-8226 10 mg/kg31400± 11.2
Week 10 (n=8,5,6,6)
GroupValue95% CI
Part 1: MK-8226 0.3 mg/kg2310± 11
Part 1: MK-8226 1 mg/kg8530± 15.4
Part 1: MK-8226 3 mg/kg21100± 28.8
Part 1: MK-8226 10 mg/kg82100± 16.2
AUC From Time 0 to Last Measurement (AUC0-last) of MK-8226 Following Multiple Intravenous Dose Administration Secondary · Days 70, 72, 74, 84, 98, 112, 140, 168, 196, 224

AUC0-last defined as AUC up to the last measured concentration was determined for the last period of dosing (starting Week 10 \[Day 70\]) up to the last measurement. MK-8226 was administered on Days 1, 14, 28, 42, 56, and 70. Blood concentrations of MK-8226 were determined on Days 70 (incl. predose), 72, 74, 84, 98, 112, 140, 168, 196, and 224. The placebo group is not included; this endpoint evaluated only the MK-8226 groups. No analysis was performed for Part 2 non-safety secondary endpoints after the Part 1 primary endpoint (Change from BL in EASI) did not demonstrate adequate effect in an

GroupValue95% CI
Part 1: MK-8226 0.3 mg/kg6460± 34.3
Part 1: MK-8226 1 mg/kg22600± 65.8
Part 1: MK-8226 3 mg/kg47100± 97.2
Part 1: MK-8226 10 mg/kg264000± 25.2
Maximum Serum Concentration (Cmax) of MK-8226 Following Multiple Dose Intravenous Administration Secondary · Days 1, 3, 5, 9, 14, 70, 72, 74, 84

Cmax was determined for the first and last periods of MK-8226 dosing. MK-8226 was administered on Days 1, 14, 28, 42, 56, and 70. Blood concentrations of MK-8226 were determined on Days 1 (incl. predose), 3, 5, 9, 14 (incl. predose), 70 (incl. predose), 72, 74, and 84. The placebo group is not included; this endpoint evaluated only the MK-8226 groups. No analysis was performed for Part 2 non-safety secondary endpoints after the Part 1 primary endpoint (Change from BL in EASI) did not demonstrate adequate effect in an interim futility analysis.

Week 1 (n=9,8,8,10)
GroupValue95% CI
Part 1: MK-8226 0.3 mg/kg7.12± 21.9
Part 1: MK-8226 1 mg/kg21.6± 26.0
Part 1: MK-8226 3 mg/kg60.3± 18.0
Part 1: MK-8226 10 mg/kg200± 12.1
Week 10 (n=8,6,6,6)
GroupValue95% CI
Part 1: MK-8226 0.3 mg/kg11.7± 9.63
Part 1: MK-8226 1 mg/kg42.4± 20.1
Part 1: MK-8226 3 mg/kg106± 19.6
Part 1: MK-8226 10 mg/kg398± 17.1
Clearance (CL) of MK-8226 Following Multiple Dose Intravenous Administration Secondary · Days 1, 3, 5, 9, 14, 28, 42, 56, 70, 72, 74, 84

CL, the volume of plasma cleared of drug per unit time, was determined for the last period of dosing (starting Week 10 \[Day 70\]) in the treatment period. MK-8226 was administered on Days 1, 14, 28, 42, 56, and 70. Blood concentrations of MK-8226 were determined on Days 1 (incl. predose), 3, 5, 9, 14 (incl. predose), 28 (incl. predose), 42 (incl. predose), 56 (incl. predose), 70 (incl. predose), 72, 74, and 84. The placebo group is not included; this endpoint evaluated only the MK-8226 groups. No analysis was performed for Part 2 non-safety secondary endpoints after the Part 1 primary endpoin

GroupValue95% CI
Part 1: MK-8226 0.3 mg/kg3.04± 11
Part 1: MK-8226 1 mg/kg2.81± 15.4
Part 1: MK-8226 3 mg/kg3.33± 28.8
Part 1: MK-8226 10 mg/kg2.9± 16.2
Volume of Distribution (Vd) of MK-8226 Following Multiple Intravenous Administration Secondary · Days 70, 72, 74, 84, 98, 112, 140, 168, 196, 224

Vd, a theoretical approximation of degree to which the drug distributes in body tissue rather than plasma (higher Vd indicates greater tissue distribution), was determined for the last period of dosing (starting Week 10 \[Day 70\]) in the treatment period. MK-8226 was administered on Days 1, 14, 28, 42, 56, and 70. Blood concentrations of MK-8226 were determined on Days 70 (incl. predose), 72, 74, 84, 98, 112, 140, 168, 196, and 224. The placebo group is not included; this endpoint evaluated only the MK-8226 groups. No analysis was performed for Part 2 non-safety secondary endpoints after the

GroupValue95% CI
Part 1: MK-8226 0.3 mg/kg103± 27.6
Part 1: MK-8226 1 mg/kg122± 26.8
Part 1: MK-8226 3 mg/kg102± 62.1
Part 1: MK-8226 10 mg/kg120± 25.3
Terminal Half Life (t1/2) of MK-8226 Following Multiple Dose Intravenous Administration Secondary · Days 70, 72, 74, 84, 98, 112, 140, 168, 196, 224

t1/2, the time needed for the concentration of drug to reach half the initial concentration, was determined for the last period of dosing (starting Week 10 \[Day 70\]) up to the last measurement. MK-8226 was administered on Days 1, 14, 28, 42, 56, and 70. Blood concentrations of MK-8226 were determined on Days 70 (incl. predose), 72, 74, 84, 98, 112, 140, 168, 196, and 224. The placebo group is not included; this endpoint evaluated only the MK-8226 groups. No analysis was performed for Part 2 non-safety secondary endpoints after the Part 1 primary endpoint (Change from BL in EASI) did not demo

GroupValue95% CI
Part 1: MK-8226 0.3 mg/kg23.6± 33.5
Part 1: MK-8226 1 mg/kg30± 15.9
Part 1: MK-8226 3 mg/kg24.7± 51.3
Part 1: MK-8226 10 mg/kg28.7± 15.7
Number of Participants Positive for Anti-Drug Antibody (ADA) Formation Secondary · Days 1 (predose) and Days 14, 28, 42, 56, 74, 112, and 224

Testing for ADA positivity and neutralizing response and antibody titre quantification are performed with blood (serum) samples collected at baseline (Day 1 predose) and Days 14, 28, 42, 56, 74, 112, and 224. Neutralizing response refers to ADA neutralizing interference with study drug assessed in vitro. Non-Treatment emergent ADA refers to presence of ADAs (as determined by assay) in the absence of treatment with study drug (i.e., at predose).

Non Treatment emergent ADA positive
GroupValue95% CI
Part 1: MK-8226 0.3 mg/kg0
Part 1: MK-8226 1 mg/kg1
Part 1: MK-8226 3 mg/kg0
Part 1: MK-8226 10 mg/kg0
Part 2: MK-8226 3 mg/kg0
Part 2: Placebo0
Treatment emergent ADA positive
GroupValue95% CI
Part 1: MK-8226 0.3 mg/kg0
Part 1: MK-8226 1 mg/kg0
Part 1: MK-8226 3 mg/kg1
Part 1: MK-8226 10 mg/kg0
Part 2: MK-8226 3 mg/kg2
Part 2: Placebo0
ADA positive: Max titer 1:10
GroupValue95% CI
Part 1: MK-8226 0.3 mg/kg0
Part 1: MK-8226 1 mg/kg0
Part 1: MK-8226 3 mg/kg0
Part 1: MK-8226 10 mg/kg0
Part 2: MK-8226 3 mg/kg0
Part 2: Placebo0
ADA positive: Max titer 1:50
GroupValue95% CI
Part 1: MK-8226 0.3 mg/kg0
Part 1: MK-8226 1 mg/kg0
Part 1: MK-8226 3 mg/kg1
Part 1: MK-8226 10 mg/kg0
Part 2: MK-8226 3 mg/kg1
Part 2: Placebo0
ADA positive: Neutralizing response positive
GroupValue95% CI
Part 1: MK-8226 0.3 mg/kg0
Part 1: MK-8226 1 mg/kg0
Part 1: MK-8226 3 mg/kg1
Part 1: MK-8226 10 mg/kg0
Part 2: MK-8226 3 mg/kg1
Part 2: Placebo0

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 32 Weeks. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Part 1: MK-8226 0.3 mg/kg
Serious: 0/9 (0%)
Deaths:
Part 1: MK-8226 1 mg/kg
Serious: 0/9 (0%)
Deaths:
Part 1: MK-8226 3 mg/kg
Serious: 0/8 (0%)
Deaths:
Part 1: MK-8226 10 mg/kg
Serious: 1/10 (10%)
Deaths:
Part 1: Placebo (Pooled)
Serious: 0/8 (0%)
Deaths:
Part 2: MK-8226 3 mg/kg
Serious: 0/13 (0%)
Deaths:
Part 2: Placebo
Serious: 1/8 (13%)
Deaths:

Serious adverse events (2 terms)

ReactionSystemPart 1: MK-8226 0.3 mg/kgPart 1: MK-8226 1 mg/kgPart 1: MK-8226 3 mg/kgPart 1: MK-8226 10 mg/kgPart 1: Placebo (Pooled)Part 2: MK-8226 3 mg/kgPart 2: Placebo
ErysipelasInfections and infestations
Abortion inducedSurgical and medical procedures
Other adverse events (78 terms — click to expand)

ReactionSystemPart 1: MK-8226 0.3 mg/kgPart 1: MK-8226 1 mg/kgPart 1: MK-8226 3 mg/kgPart 1: MK-8226 10 mg/kgPart 1: Placebo (Pooled)Part 2: MK-8226 3 mg/kgPart 2: Placebo
NasopharyngitisInfections and infestations
HeadacheNervous system disorders
Dermatitis atopicSkin and subcutaneous tissue disorders
Skin infectionInfections and infestations
Urinary tract infectionInfections and infestations
HypoacusisEar and labyrinth disorders
BlepharitisEye disorders
Conjunctivitis allergicEye disorders
Abdominal painGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
Dry mouthGastrointestinal disorders
Food poisoningGastrointestinal disorders
NauseaGastrointestinal disorders
Oral mucosal blisteringGastrointestinal disorders
Palatal swellingGastrointestinal disorders
AstheniaGeneral disorders
ChillsGeneral disorders
FatigueGeneral disorders
Gravitational oedemaGeneral disorders
Peripheral swellingGeneral disorders
PyrexiaGeneral disorders
Bacterial infectionInfections and infestations
BronchitisInfections and infestations
CellulitisInfections and infestations
ConjunctivitisInfections and infestations
FolliculitisInfections and infestations
FuruncleInfections and infestations
Gastroenteritis viralInfections and infestations
Herpes ophthalmicInfections and infestations
Herpes simplexInfections and infestations
Oral herpesInfections and infestations
Rash pustularInfections and infestations
Superinfection bacterialInfections and infestations
TonsillitisInfections and infestations
Upper respiratory tract infectionInfections and infestations
Vulvovaginal candidiasisInfections and infestations
Wound infectionInfections and infestations
ContusionInjury, poisoning and procedural complications
Joint dislocationInjury, poisoning and procedural complications
LacerationInjury, poisoning and procedural complications

Most-reported serious reactions: Erysipelas, Abortion induced.

Data from ClinicalTrials.gov NCT01732510 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. The immunology of atopic dermatitis and its reversibility with broad-spectrum and targeted therapies.
    Brunner PM, Guttman-Yassky E, Leung DY. · · 2017 · cited 471× · PMID 28390479 · DOI 10.1016/j.jaci.2017.01.011
  2. Significance of Skin Barrier Dysfunction in Atopic Dermatitis.
    Kim BE, Leung DYM. · · 2018 · cited 258× · PMID 29676067 · DOI 10.4168/aair.2018.10.3.207
  3. Thymic Stromal Lymphopoietin Isoforms, Inflammatory Disorders, and Cancer.
    Varricchi G, Pecoraro A, Marone G, Criscuolo G, et al · · 2018 · cited 171× · PMID 30057581 · DOI 10.3389/fimmu.2018.01595
  4. T cell pathology in skin inflammation.
    Sabat R, Wolk K, Loyal L, Döcke WD, et al · · 2019 · cited 134× · PMID 31028434 · DOI 10.1007/s00281-019-00742-7
  5. Immunologic, microbial, and epithelial interactions in atopic dermatitis.
    Brunner PM, Leung DYM, Guttman-Yassky E. · · 2018 · cited 129× · PMID 29126710 · DOI 10.1016/j.anai.2017.09.055
  6. The Role of TSLP in Atopic Dermatitis: From Pathogenetic Molecule to Therapeutical Target.
    Luo J, Zhu Z, Zhai Y, Zeng J, et al · · 2023 · cited 43× · PMID 37096155 · DOI 10.1155/2023/7697699
  7. The Implications of Pruritogens in the Pathogenesis of Atopic Dermatitis.
    Wong LS, Yen YT, Lee CH. · · 2021 · cited 25× · PMID 34281281 · DOI 10.3390/ijms22137227
  8. Therapeutic Advances in Diabetes, Autoimmune, and Neurological Diseases.
    Liu J, Ting JP, Al-Azzam S, Ding Y, et al · · 2021 · cited 15× · PMID 33802091 · DOI 10.3390/ijms22062805

Verify or expand the search:

Other recruiting trials for Atopic Dermatitis

Currently open trials in the same condition.

Other Merck Sharp & Dohme LLC trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT01732510.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing