Trial Outcomes & Findings for A Study to Assess the Effect of Ustekinumab (Stelara®) and Etanercept (Enbrel®) in Participants With Moderate to Severe Psoriasis (MK-0000-206) (NCT NCT01276847)
NCT ID: NCT01276847
Last Updated: 2015-01-26
Results Overview
Skin biopsies were collected from participants at baseline and after treatment with ustekinumab for 1,2,4 and 16 weeks. The expression of messenger RNA (mRNA) from three pre-defined IL-12 pathway related genes, modulated by interferon gamma (IFN-γ), namely IFN-γ, inducible nitric oxide synthase(iNOS) and CXC motif chemokine 10(CXCL10) was quantitated by real-time polymerase chain reaction (qPCR), with the data normalized by the delta-delta Ct method. The expression score for each gene, showing the percentage difference from baseline, was calculated as follows : \[(baseline - post baseline)/baseline\] x 100. Composite gene expression scores were derived for each individual by summing the expression scores of the individual genes. Positive composite scores denote a decrease from baseline in gene expression.
COMPLETED
PHASE1
40 participants
Baseline and Weeks 1, 2, 4, and 16
2015-01-26
Participant Flow
Participant milestones
| Measure |
Etanercept
Etanercept : Etanercept 50 mg twice weekly by self-administered subcutaneous injection for 12 weeks, then once weekly for 4 weeks
|
No Treatment
No treatment administered
|
Ustekinumab
Ustekinumab : Ustekinumab 45 mg per dose, administered subcutaneously for participants weighing ≤ 100 kg, and ustekinumab 90 mg per dose administered subcutaneously for participants weighing \> 100 kg on Day 1, and Weeks 4 and 16
|
|---|---|---|---|
|
Overall Study
STARTED
|
10
|
10
|
20
|
|
Overall Study
COMPLETED
|
9
|
10
|
20
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
0
|
Reasons for withdrawal
| Measure |
Etanercept
Etanercept : Etanercept 50 mg twice weekly by self-administered subcutaneous injection for 12 weeks, then once weekly for 4 weeks
|
No Treatment
No treatment administered
|
Ustekinumab
Ustekinumab : Ustekinumab 45 mg per dose, administered subcutaneously for participants weighing ≤ 100 kg, and ustekinumab 90 mg per dose administered subcutaneously for participants weighing \> 100 kg on Day 1, and Weeks 4 and 16
|
|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
0
|
Baseline Characteristics
A Study to Assess the Effect of Ustekinumab (Stelara®) and Etanercept (Enbrel®) in Participants With Moderate to Severe Psoriasis (MK-0000-206)
Baseline characteristics by cohort
| Measure |
Etanercept
n=10 Participants
Etanercept : Etanercept 50 mg twice weekly by self-administered subcutaneous injection for 12 weeks, then once weekly for 4 weeks
|
No Treatment
n=10 Participants
No treatment administered
|
Ustekinumab
n=20 Participants
Ustekinumab : Ustekinumab 45 mg per dose, administered subcutaneously for participants weighing ≤ 100 kg, and ustekinumab 90 mg per dose administered subcutaneously for participants weighing \> 100 kg on Day 1, and Weeks 4 and 16
|
Total
n=40 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
39.5 years
STANDARD_DEVIATION 12.5 • n=5 Participants
|
53.4 years
STANDARD_DEVIATION 13.0 • n=7 Participants
|
45.7 years
STANDARD_DEVIATION 12.1 • n=5 Participants
|
46.1 years
STANDARD_DEVIATION 13.1 • n=4 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
12 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
28 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline and Weeks 1, 2, 4, and 16Population: Pre-specified to be collected only in participants treated with Ustekinumab. One participant treated with Ustekinumab with extreme outlying data, likely due to mislabeling of lesional and nonlesional tissues, was excluded from the analysis.
Skin biopsies were collected from participants at baseline and after treatment with ustekinumab for 1,2,4 and 16 weeks. The expression of messenger RNA (mRNA) from three pre-defined IL-12 pathway related genes, modulated by interferon gamma (IFN-γ), namely IFN-γ, inducible nitric oxide synthase(iNOS) and CXC motif chemokine 10(CXCL10) was quantitated by real-time polymerase chain reaction (qPCR), with the data normalized by the delta-delta Ct method. The expression score for each gene, showing the percentage difference from baseline, was calculated as follows : \[(baseline - post baseline)/baseline\] x 100. Composite gene expression scores were derived for each individual by summing the expression scores of the individual genes. Positive composite scores denote a decrease from baseline in gene expression.
Outcome measures
| Measure |
Ustekinumab
n=19 Participants
Ustekinumab : Ustekinumab 45 mg per dose, administered subcutaneously for participants weighing ≤ 100 kg, and ustekinumab 90 mg per dose administered subcutaneously for participants weighing \> 100 kg on Day 1, and Weeks 4 and 16
|
|---|---|
|
Change From Baseline in Composite Gene Expression Score Based on IL-12 Pathway Related Interferon Gamma (IFN-γ)-Modulated Genes in Psoriatic Lesions of Participants Treated With Ustekinumab
Week 1
|
53.68 Gene expression score
Interval 19.9 to 96.34
|
|
Change From Baseline in Composite Gene Expression Score Based on IL-12 Pathway Related Interferon Gamma (IFN-γ)-Modulated Genes in Psoriatic Lesions of Participants Treated With Ustekinumab
Week 2
|
130.54 Gene expression score
Interval 38.47 to 158.0
|
|
Change From Baseline in Composite Gene Expression Score Based on IL-12 Pathway Related Interferon Gamma (IFN-γ)-Modulated Genes in Psoriatic Lesions of Participants Treated With Ustekinumab
Week 4
|
180.19 Gene expression score
Interval 130.5 to 189.38
|
|
Change From Baseline in Composite Gene Expression Score Based on IL-12 Pathway Related Interferon Gamma (IFN-γ)-Modulated Genes in Psoriatic Lesions of Participants Treated With Ustekinumab
Week 16
|
240.29 Gene expression score
Interval 139.44 to 257.76
|
SECONDARY outcome
Timeframe: Baseline and Weeks 1, 2, 4, and 16Population: Pre-specified to be collected only in participants treated with Ustekinumab. One participant treated with Ustekinumab with extreme outlying data, likely due to mislabeling of lesional and nonlesional tissues, was excluded from the analysis.
Skin biopsies were collected from participants at baseline and after treatment with ustekinumab for 1,2,4 and 16 weeks. The mRNA expression of eight pre-defined IL-23 pathway related genes, namely beta 4 defensin (DEFB4), CXC motif chemokine 8 (CXCL8), Interleukins 17A, 17F, 20, 22, 23A (IL-17, IL-17F, IL-20, IL-22, IL-23A) and cyclic AMP dependent protein kinase (CAMP) was quantitated by qPCR, with the data normalized by the delta-delta Ct method. The expression score for each gene, showing the percentage difference from baseline, was calculated as follows : \[(baseline - post baseline)/baseline\] x 100. Composite gene expression scores were derived for each individual by summing the expression scores of the individual genes. Positive composite scores denote a reduction from baseline in gene expression.
Outcome measures
| Measure |
Ustekinumab
n=19 Participants
Ustekinumab : Ustekinumab 45 mg per dose, administered subcutaneously for participants weighing ≤ 100 kg, and ustekinumab 90 mg per dose administered subcutaneously for participants weighing \> 100 kg on Day 1, and Weeks 4 and 16
|
|---|---|
|
Change From Baseline in Composite Gene Expression Score Based on Interleukin 23 (IL-23) Pathway Related Genes in Psoriatic Lesions of Participants Treated With Ustekinumab
Week 1
|
44.24 Gene expression score
Interval -170.81 to 185.43
|
|
Change From Baseline in Composite Gene Expression Score Based on Interleukin 23 (IL-23) Pathway Related Genes in Psoriatic Lesions of Participants Treated With Ustekinumab
Week 2
|
399.31 Gene expression score
Interval 96.66 to 442.98
|
|
Change From Baseline in Composite Gene Expression Score Based on Interleukin 23 (IL-23) Pathway Related Genes in Psoriatic Lesions of Participants Treated With Ustekinumab
Week 4
|
412.79 Gene expression score
Interval 304.55 to 550.96
|
|
Change From Baseline in Composite Gene Expression Score Based on Interleukin 23 (IL-23) Pathway Related Genes in Psoriatic Lesions of Participants Treated With Ustekinumab
Week 16
|
716.14 Gene expression score
Interval 358.51 to 746.78
|
SECONDARY outcome
Timeframe: Baseline and Weeks 1, 2, 4, and 16Population: Pre-specified to be collected only in participants treated with Etanercept.
Participants had skin biopsies performed at baseline and after treatment with etanercept for 1,2,4 and 16 weeks. The expression of IL-17 mRNA was quantitated by qPCR, with the data normalized by the delta-delta Ct method. The expression score, showing the percentage difference from baseline, was calculated as follows : \[(baseline - post baseline)/baseline\] x 100.
Outcome measures
| Measure |
Ustekinumab
n=10 Participants
Ustekinumab : Ustekinumab 45 mg per dose, administered subcutaneously for participants weighing ≤ 100 kg, and ustekinumab 90 mg per dose administered subcutaneously for participants weighing \> 100 kg on Day 1, and Weeks 4 and 16
|
|---|---|
|
Change From Baseline in Gene Expression Score for Interleukin 17 (IL-17) in Psoriatic Lesions of Participants Treated With Etanercept
Week 1
|
5.17 Gene expression score
Interval -118.88 to 15.68
|
|
Change From Baseline in Gene Expression Score for Interleukin 17 (IL-17) in Psoriatic Lesions of Participants Treated With Etanercept
Week 2
|
17.75 Gene expression score
Interval -154.28 to 44.76
|
|
Change From Baseline in Gene Expression Score for Interleukin 17 (IL-17) in Psoriatic Lesions of Participants Treated With Etanercept
Week 4
|
65.50 Gene expression score
Interval -10.94 to 84.78
|
|
Change From Baseline in Gene Expression Score for Interleukin 17 (IL-17) in Psoriatic Lesions of Participants Treated With Etanercept
Week 16
|
52.77 Gene expression score
Interval -24.74 to 91.7
|
Adverse Events
Etanercept
No Treatment
Ustekinumab
Serious adverse events
| Measure |
Etanercept
n=10 participants at risk
Etanercept : Etanercept 50 mg twice weekly by self-administered subcutaneous injection for 12 weeks, then once weekly for 4 weeks
|
No Treatment
n=10 participants at risk
No treatment administered
|
Ustekinumab
n=20 participants at risk
Ustekinumab : Ustekinumab 45 mg per dose, administered subcutaneously for participants weighing ≤ 100 kg, and ustekinumab 90 mg per dose administered subcutaneously for participants weighing \> 100 kg on Day 1, and Weeks 4 and 16
|
|---|---|---|---|
|
Pregnancy, puerperium and perinatal conditions
Foetal Distress Syndrome
|
10.0%
1/10
|
0.00%
0/10
|
0.00%
0/20
|
Other adverse events
| Measure |
Etanercept
n=10 participants at risk
Etanercept : Etanercept 50 mg twice weekly by self-administered subcutaneous injection for 12 weeks, then once weekly for 4 weeks
|
No Treatment
n=10 participants at risk
No treatment administered
|
Ustekinumab
n=20 participants at risk
Ustekinumab : Ustekinumab 45 mg per dose, administered subcutaneously for participants weighing ≤ 100 kg, and ustekinumab 90 mg per dose administered subcutaneously for participants weighing \> 100 kg on Day 1, and Weeks 4 and 16
|
|---|---|---|---|
|
Eye disorders
Vitreous Detachment
|
0.00%
0/10
|
10.0%
1/10
|
0.00%
0/20
|
|
General disorders
Cyst
|
0.00%
0/10
|
10.0%
1/10
|
0.00%
0/20
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/10
|
0.00%
0/10
|
15.0%
3/20
|
|
Infections and infestations
Pharyngitis Streptococcal
|
10.0%
1/10
|
0.00%
0/10
|
0.00%
0/20
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
0.00%
0/10
|
10.0%
1/10
|
10.0%
2/20
|
|
Injury, poisoning and procedural complications
Procedural Site Reaction
|
0.00%
0/10
|
0.00%
0/10
|
5.0%
1/20
|
|
Pregnancy, puerperium and perinatal conditions
Gestational Diabetes
|
10.0%
1/10
|
0.00%
0/10
|
0.00%
0/20
|
|
Skin and subcutaneous tissue disorders
Dermatitis Contact
|
0.00%
0/10
|
0.00%
0/10
|
5.0%
1/20
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
10.0%
1/10
|
10.0%
1/10
|
0.00%
0/20
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp.
Results disclosure agreements
- Principal investigator is a sponsor employee The SPONSOR must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the SPONSOR as confidential must be deleted prior to submission.
- Publication restrictions are in place
Restriction type: OTHER