Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04092452




Registration number
NCT04092452
Ethics application status
Date submitted
15/09/2019
Date registered
17/09/2019
Date last updated
15/06/2023

Titles & IDs
Public title
A Study to Evaluate the Safety and Efficacy of PF-06650833, PF-06700841, and PF 06826647 in Adults With Hidradenitis Suppurativa
Scientific title
A PHASE 2A, MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, 16-WEEK STUDY EVALUATING THE SAFETY AND EFFICACY OF PF-06650833, PF-06700841, AND PF-06826647 IN ADULTS WITH MODERATE TO SEVERE HIDRADENITIS SUPPURATIVA
Secondary ID [1] 0 0
C2501007
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acne Inversa 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - PF-06650833
Treatment: Drugs - PF-06700841
Treatment: Drugs - PF-06826647
Treatment: Drugs - Placebo

Experimental: Cohort 1 - PF-06650833

Experimental: Cohort 2 - PF-6700841

Experimental: Cohort 3 - PF-06826647

Placebo comparator: Cohort placebo - placebo


Treatment: Drugs: PF-06650833
400 mg QD

Treatment: Drugs: PF-06700841
45 mg QD

Treatment: Drugs: PF-06826647
400 mg QD

Treatment: Drugs: Placebo
placebo
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants Achieving Hidradenitis Suppurativa Clinical Response (HiSCR) at Week 16- Minimum Risk (MR) [Full Analysis Set (FAS), Non-responder Imputation (NRI)].
Assessment method [1] 0 0
HiSCR response was defined as at least a 50% reduction in total abscess and inflammatory nodule (AN) count relative to baseline, and no increase in abscess count, and no increase in draining fistula count. Confidence interval (CI) was calculated using Blyth-Still-Casella method.
Timepoint [1] 0 0
At week 16
Secondary outcome [1] 0 0
Percentage of Participants Achieving HiSCR Response at Weeks 1, 2, 4, 6, 8, and 12 - MR (FAS, NRI).
Assessment method [1] 0 0
HiSCR response was defined as at least a 50% reduction in total abscess and inflammatory nodule (AN) count relative to baseline, and no increase in abscess count, and no increase in draining fistula count. Confidence interval (CI) was calculated using Blyth-Still-Casella method.
Timepoint [1] 0 0
At weeks 1, 2, 4, 6, 8, and 12
Secondary outcome [2] 0 0
Percentage of Participants Achieving a Total Abscess and Inflammatory Nodule (AN) Count of 0 or 1; 0, 1 or 2 at Week 16 - MR (FAS, NRI).
Assessment method [2] 0 0
This estimand was intended to provide difference between treated and placebo in percentage of participants with a total AN count of 0 or 1, or 0, 1 or 2, respectively at week 16. Confidence interval (CI) was calculated using Blyth-Still-Casella method.
Timepoint [2] 0 0
At week 16
Secondary outcome [3] 0 0
Least Squares (LS) Mean of Percent Change From Baseline in AN Count at Weeks 1, 2, 4, 6, 8, 12 and 16 - Analysis of Covariance (ANCOVA) [FAS, Multiply Imputed (MI)].
Assessment method [3] 0 0
The analysis of covariance (ANCOVA) model was implemented for statistical testing, which included terms of treatment group, the stratification factors, and the baseline value as the independent variable.
Timepoint [3] 0 0
At weeks 1, 2, 4, 6, 8, 12 and 16
Secondary outcome [4] 0 0
Least Squares Mean of Absolute Score in International Hidradenitis Suppurativa Severity Score System (IHS4) at Weeks 1, 2, 4, 6, 8, 12 and 16 - ANCOVA (FAS, MI).
Assessment method [4] 0 0
The IHS4 score was calculated by the number of nodules, the number of abscesses, and the number of draining tunnels. IHS4 score = (number of nodules × 1) + (number of abscesses × 2) + {number of draining tunnels (fistulae/sinuses) × 4}. Confidence interval (CI) was calculated using Blyth-Still-Casella method. Lower IHS4 absolute scores mean a better outcome.
Timepoint [4] 0 0
At weeks 1, 2, 4, 6, 8, 12 and 16
Secondary outcome [5] 0 0
Least Squares Mean of Percent Change From Baseline in International Hidradenitis Suppurativa Severity Score System (IHS4) at Weeks 1, 2, 4, 6, 8, 12 and 16 - ANCOVA (FAS, MI).
Assessment method [5] 0 0
The IHS4 score was calculated by the number of nodules, the number of abscesses, and the number of draining tunnels. IHS4 score = (number of nodules × 1) + (number of abscesses × 2) + {number of draining tunnels (fistulae/sinuses) × 4}. Confidence interval (CI) was calculated using Blyth-Still-Casella method. Lower IHS4 absolute scores mean a better outcome.
Timepoint [5] 0 0
At weeks 1, 2, 4, 6, 8, 12 and 16
Secondary outcome [6] 0 0
Percentage of Participants Who Experienced a Hidradenitis Suppurativa (HS) Flare at Weeks 4, 8, 12 and 16 - MR [FAS, Only Observed Data (OBS)].
Assessment method [6] 0 0
HS flare was defined as at least a 25% increase in AN count with a minimum increase of 2 relative to Baseline. Confidence interval (CI) was calculated using Blyth-Still-Casella method.
Timepoint [6] 0 0
At weeks 4, 8, 12 and 16
Secondary outcome [7] 0 0
Percentage of Participants Achieving Skin Pain Numeric Rating Scale (NRS30), at Worst, at Weeks 1, 2, 4, 6, 8, 12 and 16 - MR (FAS With Baseline =3, NRI)
Assessment method [7] 0 0
The rate comparing treatment and placebo groups at each visit was analyzed using CMH test with MR weighting strategy between each of active treatment group and placebo. Confidence interval (CI) was calculated using Blyth-Still-Casella method. NRS30 was defined as =30% reduction and =1 unit reduction from baseline in Patient's Global Assessment (PGA) Skin Pain NRS. The range of skin pain was from 0 to 10. Lower IHS4 absolute scores mean a better outcome. Baseline was defined as the average of all values recorded between Day -6 and Day 1. Weekly data were average values of daily observations over 7 days. NRI (non-responder imputation) for missing values which were related to withdrawal and all other events except for COVID-19.
Timepoint [7] 0 0
At weeks 1, 2, 4, 6, 8, 12 and 16
Secondary outcome [8] 0 0
Percentage of Participants Achieving Skin Pain Numeric Rating Scale (NRS30), on Average, at Weeks 1, 2, 4, 6, 8, 12 and 16 - MR (FAS With Baseline =3, NRI)
Assessment method [8] 0 0
The rate comparing treatment and placebo groups at each visit was analyzed using CMH test with MR weighting strategy between each of active treatment group and placebo. Confidence interval (CI) was calculated using Blyth-Still-Casella method. NRS30 was defined as =30% reduction and =1 unit reduction from baseline in Patient's Global Assessment (PGA) Skin Pain NRS. The range of skin pain was from 0 to 10. Lower IHS4 absolute scores mean a better outcome. Baseline was defined as the average of all values recorded between Day -6 and Day 1. Weekly data were average values of daily observations over 7 days. NRI (non-responder imputation) for missing values which were related to withdrawal and all other events except for COVID-19.
Timepoint [8] 0 0
At weeks 1, 2, 4, 6, 8, 12 and 16
Secondary outcome [9] 0 0
Least Squares Mean of Percent Change From Baseline in PGA Skin Pain Numeric Rating Scale, at Worst, at Weeks 1, 2, 4, 6, 8, 12 and 16 -ANCOVA (FAS With Baseline =3, MI)
Assessment method [9] 0 0
Patient Global Assessment Skin Pain Numeric Rating Scale was used to assess the worst skin pain and the average skin pain due to HS. Ratings for the 2 items range from 0 (no skin pain) to 10 (skin pain as bad as you can imagine). These two concepts were measured within the same instrument, but were scored separately. There was no composite score for this endpoint. The higher the score, the worse the outcomes, ranging from 0 (no skin pain) to 10 (skin pain as bad as you can imagine). Subscales were not combined. The ANCOVA model was fitted. Confidence interval (CI) was calculated using Blyth-Still-Casella method.
Timepoint [9] 0 0
At weeks 1, 2, 4, 6, 8, 12 and 16
Secondary outcome [10] 0 0
Least Squares Mean of Percent Change From Baseline in PGA Skin Pain Numeric Rating Scale, on Average, at Weeks 1, 2, 4, 6, 8, 12 and 16 -ANCOVA (FAS With Baseline =3, MI)
Assessment method [10] 0 0
Patient Global Assessment Skin Pain Numeric Rating Scale was used to assess the worst skin pain and the average skin pain due to HS. Ratings for the 2 items range from 0 (no skin pain) to 10 (skin pain as bad as you can imagine). These two concepts were measured within the same instrument, but were scored separately. There was no composite score for this endpoint. The higher the score, the worse the outcomes, ranging from 0 (no skin pain) to 10 (skin pain as bad as you can imagine). Subscales were not combined. The ANCOVA model was fitted. Confidence interval (CI) was calculated using Blyth-Still-Casella method.
Timepoint [10] 0 0
At weeks 1, 2, 4, 6, 8, 12 and 16
Secondary outcome [11] 0 0
Least Squares Mean of Change From Baseline in PGA Skin Pain Numeric Rating Scale, at Worst, at Weeks 1, 2, 4, 6, 8, 12 and 16 - ANCOVA (FAS, MI)
Assessment method [11] 0 0
Patient Global Assessment Skin Pain Numeric Rating Scale was used to assess the worst skin pain and the average skin pain due to HS. Ratings for the 2 items range from 0 (no skin pain) to 10 (skin pain as bad as you can imagine). These two concepts were measured within the same instrument, but were scored separately. There was no composite score for this endpoint. The higher the score, the worse the outcomes, ranging from 0 (no skin pain) to 10 (skin pain as bad as you can imagine). Subscales were not combined. The ANCOVA model was fitted. Confidence interval (CI) was calculated using Blyth-Still-Casella method.
Timepoint [11] 0 0
At weeks 1, 2, 4, 6, 8, 12 and 16
Secondary outcome [12] 0 0
Least Squares Mean of Change From Baseline in PGA Skin Pain Numeric Rating Scale, on Average, at Weeks 1, 2, 4, 6, 8, 12 and 16 - ANCOVA (FAS, MI)
Assessment method [12] 0 0
Patient Global Assessment Skin Pain Numeric Rating Scale was used to assess the worst skin pain and the average skin pain due to HS. Ratings for the 2 items range from 0 (no skin pain) to 10 (skin pain as bad as you can imagine). These two concepts were measured within the same instrument, but were scored separately. There was no composite score for this endpoint. The higher the score, the worse the outcomes, ranging from 0 (no skin pain) to 10 (skin pain as bad as you can imagine). Subscales were not combined. The ANCOVA model was fitted. Confidence interval (CI) was calculated using Blyth-Still-Casella method.
Timepoint [12] 0 0
At weeks 1, 2, 4, 6, 8, 12 and 16
Secondary outcome [13] 0 0
Percentage of Participants Achieving Erythema Response Among Participants With Baseline Erythema Score =2 in at Least 1 Region at Weeks 1, 2, 4, 6, 8, 12 and 16 - MR (FAS, NRI)
Assessment method [13] 0 0
Erythema response was defined as achieving erythema score of 1 or 0 in all affected anatomic regions among participants who had an erythema score of 2 or more in at least 1 anatomic region at baseline. NRI for missing values which were related to withdrawal and all other events except for COVID-19. A four-point ordinal scale ranging was used: 0 (no redness), 1 (faint but discernible pink coloration), 2 (moderate red coloration), and 3 (very red or bright red coloration).
Timepoint [13] 0 0
At weeks 1, 2, 4, 6, 8, 12 and 16
Secondary outcome [14] 0 0
Number of Participants With Treatment-Emergent Adverse Events (All Causalities)
Assessment method [14] 0 0
The treatment-emergent AEs (TEAEs) were considered as an adverse event that started during the effective duration of treatment. All events that started on or after the first dosing day and time/start time, if collected, but before the last dose plus the lag time was flagged as TEAEs.
Timepoint [14] 0 0
Up to 20 weeks
Secondary outcome [15] 0 0
Number of Participants With Treatment-Emergent Adverse Events (Treatment Related)
Assessment method [15] 0 0
The treatment-emergent AEs (TEAEs) were considered as an adverse event that started during the effective duration of treatment. All events that started on or after the first dosing day and time/start time, if collected, but before the last dose plus the lag time was flagged as TEAEs.
Timepoint [15] 0 0
Up to 20 weeks
Secondary outcome [16] 0 0
Number of Participants With Incidence of Post-baseline Vital Signs of Clinical Concern - Increase From Baseline (Safety Analysis Set)
Assessment method [16] 0 0
The vital signs were measured included temperature (Oral, Tympanic, Axillary or Temporal), pulse rate (beats/min) and blood pressure (mmHg).
Timepoint [16] 0 0
Up to 20 weeks
Secondary outcome [17] 0 0
Number of Participants With Incidence of Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) (Safety Analysis Set)
Assessment method [17] 0 0
Laboratory test abnormalities included hematology, chemistry, urinalysis and biomarker.
Timepoint [17] 0 0
Up to 20 weeks
Secondary outcome [18] 0 0
Number of Participants With Incidence of Post-baseline Electrocardiogram (ECG) Values of Clinical Concern (Safety Analysis Set)
Assessment method [18] 0 0
ECG parameters included QT interval, QTc interval, PR interval, and QRS complex.
Timepoint [18] 0 0
Up to 20 weeks
Secondary outcome [19] 0 0
Least Squares Mean of Absolute Score in Hidradenitis Suppurativa (HS) Symptom Items up to Week 16 - Mixed Effect Model Repeated Measurement (MMRM) (FAS, OBS)
Assessment method [19] 0 0
The Hidradenitis Suppurativa Symptom Items were 5 single items that assessed patient self-reported symptoms related to HS. The participants were asked to rate each symptom on a 0 to 10 numerical rating scale, with 0 indicating no symptom experience and 10 indicating the worst possible symptom. The symptoms assessed include: pain, tenderness, swelling, tiredness, and bother of lesion appearance. The higher the score, the worse the outcomes, ranging from 0 indicating no symptom experience and 10 indicating the worst possible symptom. These concepts were scored separately, and were not combined into a composite score. When using mixed effect model repeated measurement (MMRM) analysis, only observed data were used and missing data were not imputed.
Timepoint [19] 0 0
At weeks 1, 2, 4, 6, 8, 12 and 16
Secondary outcome [20] 0 0
Least Squares Mean of Change From Baseline in Hidradenitis Suppurativa (HS) Symptom Items up to Week 16 - MMRM (FAS, OBS)
Assessment method [20] 0 0
The Hidradenitis Suppurativa Symptom Items were 5 single items that assessed patient self-reported symptoms related to HS. The participants were asked to rate each symptom on a 0 to 10 numerical rating scale, with 0 indicating no symptom experience and 10 indicating the worst possible symptom. The symptoms assessed include: pain, tenderness, swelling, tiredness, and bother of lesion appearance. The higher the score, the worse the outcomes, ranging from 0 indicating no symptom experience and 10 indicating the worst possible symptom. These concepts were scored separately, and were not combined into a composite score. When using mixed effect model repeated measurement (MMRM) analysis, only observed data were used and missing data were not imputed.
Timepoint [20] 0 0
At weeks 1, 2, 4, 6, 8, 12 and 16
Secondary outcome [21] 0 0
Least Squares Mean of Absolute Score in Dermatology Life Quality Index (DLQI) Total Score up to Week 16 - MMRM (FAS, OBS)
Assessment method [21] 0 0
The Dermatology Life Quality Index (DLQI) is a general dermatology questionnaire that consists of 10 items that assess patient health-related quality of life (daily activities, personal relationships, symptoms and feelings, leisure, work and school, and treatment) over the last week. Scoring for each item is on a qualitative 0 to 3 scale, with options of "Not at all", "A little", "A lot", "Very much". The scores are added up to a total composite score with the range from the minimum score of 0 to the maximum score of 30. The higher the score, the worse the outcomes.
Timepoint [21] 0 0
At weeks 4, 8, 12 and 16
Secondary outcome [22] 0 0
Least Squares Mean of Change From Baseline in DLQI Total Score up to Week 16 - MMRM (FAS, OBS)
Assessment method [22] 0 0
The Dermatology Life Quality Index (DLQI) is a general dermatology questionnaire that consists of 10 items that assess patient health-related quality of life (daily activities, personal relationships, symptoms and feelings, leisure, work and school, and treatment) over the last week. Scoring for each item is on a qualitative 0 to 3 scale, with options of "Not at all", "A little", "A lot", "Very much". The scores are added up to a total composite score with the range from the minimum score of 0 to the maximum score of 30. The higher the score, the worse the outcomes. The assessments examined a change from baseline in total score, where negative value means improvement in DLQI.
Timepoint [22] 0 0
At weeks 4, 8, 12 and 16
Secondary outcome [23] 0 0
Percentage of Participants Achieving DLQI Total Score of 0 or 1 up to Week 16 - MR (FAS With Baseline >1, NRI)
Assessment method [23] 0 0
The Dermatology Life Quality Index (DLQI) is a general dermatology questionnaire that consists of 10 items that assess patient health-related quality of life (daily activities, personal relationships, symptoms and feelings, leisure, work and school, and treatment) over the last week. Scoring for each item is on a qualitative 0 to 3 scale, with options of "Not at all", "A little", "A lot", "Very much". The scores are added up to a total composite score with the range from the minimum score of 0 to the maximum score of 30. The higher the score, the worse the outcomes. The assessments examined the percentage of patients with complete resolution of dermatology specific quality of life impact, as assessed by a total score of = 1 (range: 0 - 30), where higher percentage indicates better improvement in DLQI.
Timepoint [23] 0 0
At weeks 4, 8, 12 and 16
Secondary outcome [24] 0 0
Plasma Concentration Versus Time Summary (Pharmacokinetic Concentration Set)
Assessment method [24] 0 0
In summary statistics for pharmacokinetic, concentration values below the lower limit of quantification (LLOQ) was set to zero.
Timepoint [24] 0 0
At weeks 1, 2, 4, 6, 8, 12 and 16

Eligibility
Key inclusion criteria
* male or female participants, between 18-75, with a diagnosis of moderate to severe Hidradenitis Suppurativa
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* History of human immunodeficiency virus (HIV) or positive HIV serology at screening,
* Infected with hepatitis B or hepatitis C viruses.
* Have evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis (TB)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
2/12/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
10/01/2022
Sample size
Target
Accrual to date
Final
194
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,VIC
Recruitment hospital [1] 0 0
Woden Dermatology - Phillip
Recruitment hospital [2] 0 0
Premier Specialists Pty Ltd - Kogarah
Recruitment hospital [3] 0 0
Holdsworth House Medical Practice - Sydney
Recruitment hospital [4] 0 0
Veracity Clinical Research - Woolloongabba
Recruitment hospital [5] 0 0
Skin Health Institute Inc. - Carlton
Recruitment hospital [6] 0 0
Sinclair Dermatology - East Melbourne
Recruitment postcode(s) [1] 0 0
2606 - Phillip
Recruitment postcode(s) [2] 0 0
2217 - Kogarah
Recruitment postcode(s) [3] 0 0
2010 - Sydney
Recruitment postcode(s) [4] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [5] 0 0
3053 - Carlton
Recruitment postcode(s) [6] 0 0
3002 - East Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Indiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Kentucky
Country [10] 0 0
United States of America
State/province [10] 0 0
Massachusetts
Country [11] 0 0
United States of America
State/province [11] 0 0
Michigan
Country [12] 0 0
United States of America
State/province [12] 0 0
Minnesota
Country [13] 0 0
United States of America
State/province [13] 0 0
Missouri
Country [14] 0 0
United States of America
State/province [14] 0 0
Nebraska
Country [15] 0 0
United States of America
State/province [15] 0 0
Nevada
Country [16] 0 0
United States of America
State/province [16] 0 0
New York
Country [17] 0 0
United States of America
State/province [17] 0 0
Oklahoma
Country [18] 0 0
United States of America
State/province [18] 0 0
Pennsylvania
Country [19] 0 0
United States of America
State/province [19] 0 0
Tennessee
Country [20] 0 0
United States of America
State/province [20] 0 0
Texas
Country [21] 0 0
United States of America
State/province [21] 0 0
Utah
Country [22] 0 0
United States of America
State/province [22] 0 0
Virginia
Country [23] 0 0
United States of America
State/province [23] 0 0
Washington
Country [24] 0 0
Canada
State/province [24] 0 0
Ontario
Country [25] 0 0
Canada
State/province [25] 0 0
Quebec

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pfizer
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT04092452