Trial Outcomes & Findings for IL1-TRAP, Rilonacept, in Systemic Sclerosis (NCT NCT01538719)
NCT ID: NCT01538719
Last Updated: 2018-05-01
Results Overview
To investigate the effect of rilonacept on 2-gene biomarker expression in skin after treatment with rilonacept compared to pre-treatment 2-gene biomarker expression. These were measured at visit 3 (Day 42) and visit 1 (Day 0). This was calculated using a previously validated equation (MRSS = -27.6844 + \[4.46(baseline THBS1)\] + \[5.31(ΔMS4A4A) + 4.96(ΔTHBS1)\]). In this equation the expression of two genes (THBS1 and MS4A4) in collected samples are measured via nanostring, and then the expression levels of each gene are inserted into the equation in order to obtain the 2- gene biomarker score. A high biomarker score is equivalent to a high skin score, suggesting a higher severity of the disease.
COMPLETED
PHASE1/PHASE2
24 participants
Visit 3 (Day 42) - Visit 1 (Day 0)
2018-05-01
Participant Flow
2 subjects withdrew consent and 3 found to be ineligible, leaving 19 for randomization.
Participant milestones
| Measure |
Placebo
2:1 randomization
Placebo: Patients randomized to placebo will receive saline subcutaneously (SQ) on day 0 and each week for 5 additional weeks
|
Rilonacept
2:1 randomization
Rilonacept: Patients randomized to active study drug will receive Rilonacept 320 mg subcutaneously (SQ) on day 0 and 160 mg SQ each week for 5 additional weeks
|
|---|---|---|
|
Overall Study
STARTED
|
7
|
12
|
|
Overall Study
COMPLETED
|
5
|
12
|
|
Overall Study
NOT COMPLETED
|
2
|
0
|
Reasons for withdrawal
| Measure |
Placebo
2:1 randomization
Placebo: Patients randomized to placebo will receive saline subcutaneously (SQ) on day 0 and each week for 5 additional weeks
|
Rilonacept
2:1 randomization
Rilonacept: Patients randomized to active study drug will receive Rilonacept 320 mg subcutaneously (SQ) on day 0 and 160 mg SQ each week for 5 additional weeks
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
2
|
0
|
Baseline Characteristics
IL1-TRAP, Rilonacept, in Systemic Sclerosis
Baseline characteristics by cohort
| Measure |
Placebo
n=7 Participants
2:1 randomization
Placebo: Patients randomized to placebo will receive saline subcutaneously (SQ) on day 0 and each week for 5 additional weeks
|
Rilonacept
n=12 Participants
2:1 randomization
Rilonacept: Patients randomized to active study drug will receive Rilonacept 320 mg subcutaneously (SQ) on day 0 and 160 mg SQ each week for 5 additional weeks
|
Total
n=19 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
49.86 years
STANDARD_DEVIATION 11.10 • n=5 Participants
|
51.33 years
STANDARD_DEVIATION 7.33 • n=7 Participants
|
50.79 years
STANDARD_DEVIATION 8.63 • n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
7 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Visit 3 (Day 42) - Visit 1 (Day 0)Population: Analysis run on 4 available samples in placebo arm.
To investigate the effect of rilonacept on 2-gene biomarker expression in skin after treatment with rilonacept compared to pre-treatment 2-gene biomarker expression. These were measured at visit 3 (Day 42) and visit 1 (Day 0). This was calculated using a previously validated equation (MRSS = -27.6844 + \[4.46(baseline THBS1)\] + \[5.31(ΔMS4A4A) + 4.96(ΔTHBS1)\]). In this equation the expression of two genes (THBS1 and MS4A4) in collected samples are measured via nanostring, and then the expression levels of each gene are inserted into the equation in order to obtain the 2- gene biomarker score. A high biomarker score is equivalent to a high skin score, suggesting a higher severity of the disease.
Outcome measures
| Measure |
Placebo
n=4 Participants
2:1 randomization
Placebo: Patients randomized to placebo will receive saline subcutaneously (SQ) on day 0 and each week for 5 additional weeks
|
Rilonacept
n=12 Participants
2:1 randomization
Rilonacept: Patients randomized to active study drug will receive Rilonacept 320 mg subcutaneously (SQ) on day 0 and 160 mg SQ each week for 5 additional weeks
|
|---|---|---|
|
Change in 2- Gene Biomarker
|
-2.67 2- gene biomarkers score
Interval -5.92 to 0.57
|
0.42 2- gene biomarkers score
Interval -2.97 to 3.82
|
SECONDARY outcome
Timeframe: Visit 3 (Day 42) - Visit 1 (Day 0)Change in Modified Rodnan Skin Score over time. The fully validated modified version of the Rodnan skin thickness score was used. On this scale, a total of 17 skin sites are evaluated, including the face, upper arms, forearms, dorsum of the hands, fingers, chest, abdomen, thighs, forearms and feet. The total score can range from 0 to 51, with higher scores indicating greater severity of skin thickening and involvement (MRSS-51). Each of the 17 skin sites are scored from 0 to 3, where the following criteria apply: 0, normal skin; 1, thickened skin; 2, thickened and unable to pinch; and 3, thickened and unable to move. Scores from visit 3 (Day 42) and visit 1 (Day 0) were compared.
Outcome measures
| Measure |
Placebo
n=7 Participants
2:1 randomization
Placebo: Patients randomized to placebo will receive saline subcutaneously (SQ) on day 0 and each week for 5 additional weeks
|
Rilonacept
n=12 Participants
2:1 randomization
Rilonacept: Patients randomized to active study drug will receive Rilonacept 320 mg subcutaneously (SQ) on day 0 and 160 mg SQ each week for 5 additional weeks
|
|---|---|---|
|
Change in Modified Rodnan Skin Score
|
-0.4 Units on the Modified Rodnan Skin Score
Interval -5.0 to 9.0
|
-0.6667 Units on the Modified Rodnan Skin Score
Interval -5.0 to 14.0
|
Adverse Events
Placebo
Rilonacept
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=7 participants at risk
2:1 randomization
Placebo: Patients randomized to placebo will receive saline subcutaneously (SQ) on day 0 and each week for 5 additional weeks
|
Rilonacept
n=12 participants at risk
2:1 randomization
Rilonacept: Patients randomized to active study drug will receive Rilonacept 320 mg subcutaneously (SQ) on day 0 and 160 mg SQ each week for 5 additional weeks
|
|---|---|---|
|
Skin and subcutaneous tissue disorders
Pain
|
14.3%
1/7 • Adverse events were collected from screening (Day -28) up to study completion (visit 4 / Day 84)
|
0.00%
0/12 • Adverse events were collected from screening (Day -28) up to study completion (visit 4 / Day 84)
|
|
Skin and subcutaneous tissue disorders
Allergic Reaction on Abdomen
|
0.00%
0/7 • Adverse events were collected from screening (Day -28) up to study completion (visit 4 / Day 84)
|
8.3%
1/12 • Adverse events were collected from screening (Day -28) up to study completion (visit 4 / Day 84)
|
|
Skin and subcutaneous tissue disorders
Digital Ulcer Worsening
|
0.00%
0/7 • Adverse events were collected from screening (Day -28) up to study completion (visit 4 / Day 84)
|
8.3%
1/12 • Adverse events were collected from screening (Day -28) up to study completion (visit 4 / Day 84)
|
|
Skin and subcutaneous tissue disorders
Abscess on Back
|
0.00%
0/7 • Adverse events were collected from screening (Day -28) up to study completion (visit 4 / Day 84)
|
8.3%
1/12 • Adverse events were collected from screening (Day -28) up to study completion (visit 4 / Day 84)
|
|
Skin and subcutaneous tissue disorders
Left Breast Swelling
|
0.00%
0/7 • Adverse events were collected from screening (Day -28) up to study completion (visit 4 / Day 84)
|
8.3%
1/12 • Adverse events were collected from screening (Day -28) up to study completion (visit 4 / Day 84)
|
|
General disorders
Malaise
|
14.3%
1/7 • Adverse events were collected from screening (Day -28) up to study completion (visit 4 / Day 84)
|
0.00%
0/12 • Adverse events were collected from screening (Day -28) up to study completion (visit 4 / Day 84)
|
|
Skin and subcutaneous tissue disorders
Injection Site Reaction
|
0.00%
0/7 • Adverse events were collected from screening (Day -28) up to study completion (visit 4 / Day 84)
|
16.7%
2/12 • Adverse events were collected from screening (Day -28) up to study completion (visit 4 / Day 84)
|
|
General disorders
Fatigue
|
0.00%
0/7 • Adverse events were collected from screening (Day -28) up to study completion (visit 4 / Day 84)
|
16.7%
2/12 • Adverse events were collected from screening (Day -28) up to study completion (visit 4 / Day 84)
|
|
Skin and subcutaneous tissue disorders
Infection
|
0.00%
0/7 • Adverse events were collected from screening (Day -28) up to study completion (visit 4 / Day 84)
|
8.3%
1/12 • Adverse events were collected from screening (Day -28) up to study completion (visit 4 / Day 84)
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/7 • Adverse events were collected from screening (Day -28) up to study completion (visit 4 / Day 84)
|
8.3%
1/12 • Adverse events were collected from screening (Day -28) up to study completion (visit 4 / Day 84)
|
Additional Information
Eric A Stratton, Sr. Clinical Research Manager
Boston University School of Medicine
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place