Hidradenitis Suppurativa
Conditions
Brief summary
The purpose of this study is to gain initial evidence for the safety, tolerability and efficacy of MEDI8968 for the treatment of subjects with moderate to severe hidradenitis suppurativa
Interventions
BIOLOGICALMEDI8968
SC injection at baseline, Week 4 and Week 8
BIOLOGICALSaline
SC injection at baseline, Week 4 and Week 8
Sponsors
ICON plc
Covance
PHT Corporation
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Hidradenitis suppurativa (HS) (moderate to severe) * Diagnosis of HS for at least 1 year * At least 5 active inflammatory lesions in at least 2 locations * On a stable dose of antibiotics and/or analgesics for at least 4 weeks (if already taking these medications) * Average pain score of 3-9.
Exclusion criteria
* History of cyclic neutropenia * Laboratory assessment abnormalities * Underlying disorder considered unsuitable for inclusion * Other skin diseases that may interfere with HS assessment * Pregnancy or planning for pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 1) Percentage of Subjects Achieving a Clinically Relevant Response in Physician Global Assessment (PGA), With Score 0,1 or 2 From Baseline to 12 Weeks | 12 weeks | Percentage of subjects achieving a clinically significant response measured by the proportion of subjects who achieve 0, 1, or 2 PGA by the end of week 12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 2) Subject's Global Impression of Change Reported on PGIC Scale (1-7 Point Scale Ranging From 1 Very Much Improved to 7 Very Much Worse) | 12 weeks | Percentage of subjects achieving a clinically significant response measured by the proportion of subjects who are minimally improved, much improved or very much improved on the Patient's Global Impression of Change (PGIC) |
| Change From Baseline to 12 Weeks in Numerical Assessment Scale Numerical Rating Scale for Pain | 12 weeks | Assessment of change in pain via Numerical Rating Scale. Daily pain is reported by the subject using an 11-point 0 (no pain) to 10 (worst pain imaginable) numeric rating scale. Baseline score is the average of the values collected in the 7 days prior to first dose of study drug. Each Visit score is the average of the values collected in the 7 days prior to that visit. |
Countries
United States
Participant flow
Recruitment details
221 subjects enrolled, 109 randomised. Enrolment for ERF based on info databased, as per programmed outputs and the CSR - the criteria being to have provided written consent. 3 additional patients were accounted for in the PRF. M and F subjects with moderate to severe HS were randomised to MEDI8968 or Placebo. 29 centres in the US involved.
Pre-assignment details
Randomisation to treatment was stratified by PGA score on the day of randomisation (Stratum 1=PGA score of 3; Stratum 2=PGA score of 4 or 5).
Participants by arm
| Arm | Count |
|---|---|
| MEDI8968 SC injection | 55 |
| Saline SC injection | 54 |
| Total | 109 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 |
| Overall Study | Lack of Efficacy | 1 | 2 |
| Overall Study | Lost to Follow-up | 2 | 4 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 19 | 9 |
Baseline characteristics
| Characteristic | MEDI8968 | Saline | Total |
|---|---|---|---|
| Age, Continuous | 37.5 Years STANDARD_DEVIATION 11.08 | 36.4 Years STANDARD_DEVIATION 12.42 | 36.9 Years STANDARD_DEVIATION 11.72 |
| Sex: Female, Male Female | 45 Participants | 38 Participants | 83 Participants |
| Sex: Female, Male Male | 10 Participants | 16 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 55 | 2 / 54 |
| serious Total, serious adverse events | 2 / 55 | 2 / 54 |
Outcome results
Primary
1) Percentage of Subjects Achieving a Clinically Relevant Response in Physician Global Assessment (PGA), With Score 0,1 or 2 From Baseline to 12 Weeks
Percentage of subjects achieving a clinically significant response measured by the proportion of subjects who achieve 0, 1, or 2 PGA by the end of week 12
Time frame: 12 weeks
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MEDI8968 | 1) Percentage of Subjects Achieving a Clinically Relevant Response in Physician Global Assessment (PGA), With Score 0,1 or 2 From Baseline to 12 Weeks | Responders (%) | 23.6 % of patients |
| MEDI8968 | 1) Percentage of Subjects Achieving a Clinically Relevant Response in Physician Global Assessment (PGA), With Score 0,1 or 2 From Baseline to 12 Weeks | Non-responders (%) | 76.4 % of patients |
| Saline | 1) Percentage of Subjects Achieving a Clinically Relevant Response in Physician Global Assessment (PGA), With Score 0,1 or 2 From Baseline to 12 Weeks | Responders (%) | 18.5 % of patients |
| Saline | 1) Percentage of Subjects Achieving a Clinically Relevant Response in Physician Global Assessment (PGA), With Score 0,1 or 2 From Baseline to 12 Weeks | Non-responders (%) | 81.5 % of patients |
Comparison: Analysis of proportion of Responders for Physician's Global Assessment (PGA score 0, 1 or 2) at Week 12 - LOCF. Difference in proportions MEDI8968 - placebo. Wald asymptotic confidence limits calculated.p-value: >0.0580% CI: [-0.067, 0.169]Mixed Models Analysis
Secondary
2) Subject's Global Impression of Change Reported on PGIC Scale (1-7 Point Scale Ranging From 1 Very Much Improved to 7 Very Much Worse)
Percentage of subjects achieving a clinically significant response measured by the proportion of subjects who are minimally improved, much improved or very much improved on the Patient's Global Impression of Change (PGIC)
Time frame: 12 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MEDI8968 | 2) Subject's Global Impression of Change Reported on PGIC Scale (1-7 Point Scale Ranging From 1 Very Much Improved to 7 Very Much Worse) | Responders (%) | 49.1 % of patients |
| MEDI8968 | 2) Subject's Global Impression of Change Reported on PGIC Scale (1-7 Point Scale Ranging From 1 Very Much Improved to 7 Very Much Worse) | Non-Responders (%) | 50.9 % of patients |
| Saline | 2) Subject's Global Impression of Change Reported on PGIC Scale (1-7 Point Scale Ranging From 1 Very Much Improved to 7 Very Much Worse) | Responders (%) | 55.6 % of patients |
| Saline | 2) Subject's Global Impression of Change Reported on PGIC Scale (1-7 Point Scale Ranging From 1 Very Much Improved to 7 Very Much Worse) | Non-Responders (%) | 44.4 % of patients |
Comparison: Difference in proportions MEDI8968 - placebo. Wald asymptotic confidence limits calculated.p-value: >0.0580% CI: [-0.205, 0.076]Mixed Models Analysis
Secondary
Change From Baseline to 12 Weeks in Numerical Assessment Scale Numerical Rating Scale for Pain
Assessment of change in pain via Numerical Rating Scale. Daily pain is reported by the subject using an 11-point 0 (no pain) to 10 (worst pain imaginable) numeric rating scale. Baseline score is the average of the values collected in the 7 days prior to first dose of study drug. Each Visit score is the average of the values collected in the 7 days prior to that visit.
Time frame: 12 weeks
Population: FAS (LOCF)
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| MEDI8968 | Change From Baseline to 12 Weeks in Numerical Assessment Scale Numerical Rating Scale for Pain | Week 4 | -1.09 changes in scores on a scale | Standard Error 0.35 |
| MEDI8968 | Change From Baseline to 12 Weeks in Numerical Assessment Scale Numerical Rating Scale for Pain | Week 8 | -1.76 changes in scores on a scale | Standard Error 0.36 |
| MEDI8968 | Change From Baseline to 12 Weeks in Numerical Assessment Scale Numerical Rating Scale for Pain | Week 12 | -1.79 changes in scores on a scale | Standard Error 0.46 |
| Saline | Change From Baseline to 12 Weeks in Numerical Assessment Scale Numerical Rating Scale for Pain | Week 8 | -1.31 changes in scores on a scale | Standard Error 0.36 |
| Saline | Change From Baseline to 12 Weeks in Numerical Assessment Scale Numerical Rating Scale for Pain | Week 4 | -1.02 changes in scores on a scale | Standard Error 0.36 |
| Saline | Change From Baseline to 12 Weeks in Numerical Assessment Scale Numerical Rating Scale for Pain | Week 12 | -1.76 changes in scores on a scale | Standard Error 0.47 |
Comparison: Analysis of change from baseline (Week 12) estimated from ANCOVA model with tmt group and PGA stratum at randomisation included in the model and average daily pain at baseline as a covariatep-value: 0.94580% CI: [-0.63, 0.57]ANCOVA