Trial Outcomes & Findings for The Immunological Basis for Treatment Resistance to Anti-TNF Treatments (NCT NCT01971346)

NCT ID: NCT01971346

Last Updated: 2020-03-04

Results Overview

A cumulative change in PASI score from baseline to week 12 will be calculated for each patient. The PASI is the industry standard to decrease/eliminate subjectivity in determining psoriasis severity. It is a quantitative rating scale for measuring the severity of psoriatic lesions based on area coverage and plaque appearance. The severity of plaque characteristics (erythema, thickness and scaling) for body regions (head, upper limbs, trunk and lower limbs) is combined with the degree of plaque involvement in each body region to determine a single PASI score in the range of 0 (no disease) and 72 (maximal disease).

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

50 participants

Primary outcome timeframe

Baseline, 12 weeks

Results posted on

2020-03-04

Participant Flow

Participant milestones

Participant milestones
Measure	Etanercept 100 mg Etanercept injections per week for 3 months. etanercept: 100 mg Etanercept injections per week (2 separate single-use pre-filled 50 mg subcutaneous injections taken on two separate days) for 3 months
Overall Study STARTED	50
Overall Study COMPLETED	42
Overall Study NOT COMPLETED	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Etanercept 100 mg Etanercept injections per week for 3 months. etanercept: 100 mg Etanercept injections per week (2 separate single-use pre-filled 50 mg subcutaneous injections taken on two separate days) for 3 months
Overall Study Protocol Violation	3
Overall Study Lost to Follow-up	2
Overall Study Withdrawal by Subject	2
Overall Study Physician Decision	1

Baseline Characteristics

Biopsy not completed on one subject. Tissue was not worked up/unable to be processed for two subjects.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Etanercept n=46 Participants 100 mg Etanercept injections per week for 3 months. etanercept: 100 mg Etanercept injections per week (2 separate single-use pre-filled 50 mg subcutaneous injections taken on two separate days) for 3 months
Age, Continuous	40.83 years n=46 Participants
Sex: Female, Male Female	17 Participants n=46 Participants
Sex: Female, Male Male	29 Participants n=46 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=46 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	38 Participants n=46 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=46 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=46 Participants
Race (NIH/OMB) Asian	1 Participants n=46 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=46 Participants
Race (NIH/OMB) Black or African American	0 Participants n=46 Participants
Race (NIH/OMB) White	44 Participants n=46 Participants
Race (NIH/OMB) More than one race	1 Participants n=46 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=46 Participants
Psoriasis Area and Severity Index (PASI) Score	14.16 units on a scale n=46 Participants
Tumor Necrosis Factor (TNF)-alpha Signal	111.33 rpkm n=43 Participants • Biopsy not completed on one subject. Tissue was not worked up/unable to be processed for two subjects.
Interferon (IFN)-alpha Signal	2118.20 rpkm n=43 Participants • Biopsy not completed on one subject. Tissue was not worked up/unable to be processed for two subjects.

PRIMARY outcome

Timeframe: Baseline, 12 weeks

Population: Only those subjects who finished the study (have a Week 0 and Week 12 visit with recorded PASI) are included in the analysis assessing a change from baseline.

Outcome measures

Outcome measures
Measure	PASI Score at Week 0 n=42 Participants PASI will be measured at the baseline visit before treatment.	PASI Score at Week 12 n=42 Participants PASI will be measured at the Week 12 visit after the course of etanercept treatment.	TNF-alpha Signal Strength at Week 12 Strength of TNF-alpha signature measured in skin of study subjects at Week 12.
Change in Psoriasis Area and Severity Index (PASI) Score	13.92 units on a scale Standard Error 1.11	4.43 units on a scale Standard Error 0.48	—

SECONDARY outcome

Timeframe: Baseline, Week 6, Week 12

Population: PASI response profile is only done for those subjects who completed the study, n=42. Biopsy not completed on one subject at baseline. Tissue not able to be processed for two subjects at baseline, Week 6 and Week 12. Biopsy not completed on three subjects at Week 6 visit. Biopsy not completed on three different subjects at Week 12 visit.

Strength of TNF-alpha signatures will be measured in skin of study subjects at initiation, during and after treatment. The strength of these signals will be done using bioinformatic approach quantifying transcriptional signature of these cytokines. The strength of the cytokine signals will be treated as a response variable in a univariate repeated measure analysis of variance, with PASI response profile and time as covariates. PASI response profile will be categorized according to improvement in PASI score: responders (greater than 75% reduction in PASI from baseline), intermediate-responders (those with greater than 25% and less than 75% reduction in PASI from baseline), and non-responders (less than 25% reduction in PASI from baseline).

Outcome measures

Outcome measures
Measure	PASI Score at Week 0 n=39 Participants PASI will be measured at the baseline visit before treatment.	PASI Score at Week 12 n=37 Participants PASI will be measured at the Week 12 visit after the course of etanercept treatment.	TNF-alpha Signal Strength at Week 12 n=37 Participants Strength of TNF-alpha signature measured in skin of study subjects at Week 12.
Tumor Necrosis Factor (TNF)-Alpha Signal Strength PASI Responder	98.26 rpkm Standard Error 7.40	85.82 rpkm Standard Error 10.34	64.157 rpkm Standard Error 8.99
Tumor Necrosis Factor (TNF)-Alpha Signal Strength PASI Intermediate-Responder	107.79 rpkm Standard Error 6.04	108.02 rpkm Standard Error 8.44	92.01 rpkm Standard Error 7.34
Tumor Necrosis Factor (TNF)-Alpha Signal Strength PASI Non-Responder	110.62 rpkm Standard Error 14.79	103.68 rpkm Standard Error 20.67	123.08 rpkm Standard Error 17.98

SECONDARY outcome

Timeframe: Baseline, Week 6, Week 12

Strength of IFN-alpha signatures will be measured in skin of study subjects at initiation, during and after treatment. The strength of these signals in skin will be done using bioinformatic approach quantifying transcriptional signature of these cytokines. The strength of the cytokine signals will be treated as a response variable in a univariate repeated measure analysis of variance, with PASI response profile and time as covariates. PASI response profile will be categorized according to improvement in PASI score: responders (greater than 75% reduction in PASI from baseline), intermediate-responders (those with greater than 25% and less than 75% reduction in PASI from baseline), and non-responders (less than 25% reduction in PASI from baseline).

Outcome measures

Outcome measures
Measure	PASI Score at Week 0 n=39 Participants PASI will be measured at the baseline visit before treatment.	PASI Score at Week 12 n=37 Participants PASI will be measured at the Week 12 visit after the course of etanercept treatment.	TNF-alpha Signal Strength at Week 12 n=37 Participants Strength of TNF-alpha signature measured in skin of study subjects at Week 12.
Interferon (IFN)-Alpha Signal Strength PASI Responder	2082.72 rpkm Standard Error 70.73	2146.83 rpkm Standard Error 84.18	2180.36 rpkm Standard Error 88.46
Interferon (IFN)-Alpha Signal Strength PASI Intermediate-Responder	2106.72 rpkm Standard Error 57.75	2186.17 rpkm Standard Error 68.73	2107.22 rpkm Standard Error 72.23
Interferon (IFN)-Alpha Signal Strength PASI Non-Responder	2102.64 rpkm Standard Error 141.46	2035.94 rpkm Standard Error 168.36	1923.33 rpkm Standard Error 176.92

SECONDARY outcome

Timeframe: 12 Weeks

Subjects will be categorized according to improvement in Psoriasis Area and Severity Index (PASI) score: responders (greater than 75% reduction in PASI from baseline), intermediate-responders (those with greater than 25% and less than 75% reduction in PASI from baseline), and non-responders (less than 25% reduction in PASI from baseline).

Outcome measures

Outcome measures
Measure	PASI Score at Week 0 n=42 Participants PASI will be measured at the baseline visit before treatment.	PASI Score at Week 12 PASI will be measured at the Week 12 visit after the course of etanercept treatment.	TNF-alpha Signal Strength at Week 12 Strength of TNF-alpha signature measured in skin of study subjects at Week 12.
Psoriasis Area and Severity Index (PASI) Response Profile Responders	19 Participants	—	—
Psoriasis Area and Severity Index (PASI) Response Profile Intermediate Responders	20 Participants	—	—
Psoriasis Area and Severity Index (PASI) Response Profile Non-Responders	3 Participants	—	—

Adverse Events

Etanercept

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Etanercept n=46 participants at risk 100 mg Etanercept injections per week for 3 months. etanercept: 100 mg Etanercept injections per week (2 separate single-use pre-filled 50 mg subcutaneous injections taken on two separate days) for 3 months
Gastrointestinal disorders Post-Op Constipation	2.2% 1/46 • Number of events 1 • Adverse Event data was collected during the study period time between baseline visit and final visit, 12 weeks. Adverse events, start date and time, end date, severity, outcome, relation to study drug, relation to study procedure and severity were assessed, collected and recorded in Adverse Event (AE) log by study staff at each visit. The total number of participants at risk includes only those subjects who received study drug at baseline visit. Four subjects consented and withdrew from the study prior to study drug administration; therefore, they were not considered at risk.

Other adverse events

Other adverse events
Measure	Etanercept n=46 participants at risk 100 mg Etanercept injections per week for 3 months. etanercept: 100 mg Etanercept injections per week (2 separate single-use pre-filled 50 mg subcutaneous injections taken on two separate days) for 3 months
Respiratory, thoracic and mediastinal disorders Nasal Congestion	8.7% 4/46 • Number of events 4 • Adverse Event data was collected during the study period time between baseline visit and final visit, 12 weeks. Adverse events, start date and time, end date, severity, outcome, relation to study drug, relation to study procedure and severity were assessed, collected and recorded in Adverse Event (AE) log by study staff at each visit. The total number of participants at risk includes only those subjects who received study drug at baseline visit. Four subjects consented and withdrew from the study prior to study drug administration; therefore, they were not considered at risk.
Skin and subcutaneous tissue disorders Injection Site Reaction	6.5% 3/46 • Number of events 3 • Adverse Event data was collected during the study period time between baseline visit and final visit, 12 weeks. Adverse events, start date and time, end date, severity, outcome, relation to study drug, relation to study procedure and severity were assessed, collected and recorded in Adverse Event (AE) log by study staff at each visit. The total number of participants at risk includes only those subjects who received study drug at baseline visit. Four subjects consented and withdrew from the study prior to study drug administration; therefore, they were not considered at risk.
Gastrointestinal disorders GI Distress	6.5% 3/46 • Number of events 3 • Adverse Event data was collected during the study period time between baseline visit and final visit, 12 weeks. Adverse events, start date and time, end date, severity, outcome, relation to study drug, relation to study procedure and severity were assessed, collected and recorded in Adverse Event (AE) log by study staff at each visit. The total number of participants at risk includes only those subjects who received study drug at baseline visit. Four subjects consented and withdrew from the study prior to study drug administration; therefore, they were not considered at risk.

Additional Information

Heather Chubb

University of Michigan

Phone: 734-936-6394

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place