A Study In Adults With Moderate To Severe Dermatomyositis

Phase 2

Completed

Conditions: Dermatomyositis

Interventions: Drug: Placebo Arm
Drug: PF-06823859 low
Drug: PF-06823859 high

Registration Number: NCT03181893

Lead Sponsor: Pfizer

Brief Summary: A Study looking at Investigational drug and Placebo administered to adult Patients with moderate to severe Dermatomyositis

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 75

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo ARM	Placebo Arm	-
PF-06823859 ARM low	PF-06823859 low	-
PF-06823859 ARM high	PF-06823859 high	-

Primary Outcome Measures

Name	Time	Method
Number of Participants With Vital Sign Abnormalities (Stage 3)	Baseline up to Week 40	Abnormality in vital signs: Sitting pulse rate \<40 beats per minute (bpm) to \>120 bpm, sitting diastolic blood pressure (DBP) \< 50 millimeter of mercury (mmHg), sitting systolic blood pressure (SBP) \<90 mmHg.
Change From Baseline in Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) Activity Score at Week 12 (Stage 1, Stage 2 and Amended Stage 2)	Baseline and Week 12	The treatment effect was defined as the difference (mean chg from baseline at Week12 in the active treatment group minus that in the placebo group) in the mean change of CDASI activity score from baseline at Week 12. The score (range: 0-100) consists of the extent score (ES), Gottorn hands score (GHS), peringual score (PS) and allopecia score (AS). ES (range: 0-90) was obtained by summing up scores for the total erythema (ER \[0-45\], redness of the skin or mucous membranes), scaling (SC \[0-30\], peeling of the skin) and erosion/ulceration (EU \[0-15\], presence of the deeper wound). Total ER, SC and EU scores were calculated as a sum of the contributions from 15 individual areas of the body. GHS characterizes papules (swellings) on hand and is a sum of the papule's characterization score (0-6) and ulceration score (0-1). PS (0-2) characterizes abnormalities around nails. The AS (0-1) characterizes hair loss. Higher scores indicate greater disease severity.
Number of Participants With Electrocardiogram (ECG) Abnormalities (Stage 3)	Baseline up to Week 40	ECG abnormalities criteria included: 1) QTc interval adjusted according to Fridericia formula (QTcF) (msec): \>450, \>480, \>500, increase from baseline \>=30, increase from baseline \>=60; 2) Pulse rate (PR) (msec): \>=300, change from baseline (Chg) \>=25% or 50%; 3) QT (msec): \>=500; 4) QRS (msec): \>=200, Chg \>=25% or 50%. Categories, with at least 1 participant having ECG abnormality in any of the reporting arms, were reported in this outcome measure.
Number of Participants With Clinically Significant Laboratory Abnormalities (Stage 3)	Up to Week 40	Hemoglobin(HGB),hematocrit,erythrocytes(ery.),HDL cholesterol(chl.)\<0.8\lower limit of normal(LLN);reticulocytes (ret.), ret./ery.(%)\<0.5\LLN,\>1.5\upper limit of normal (ULN);ery. mean corpuscular(EMC) volume,EMC HGB concentration,potassium,chloride,calcium,bicarbonate\<0.9\LLN,\>1.1\ULN;platelets\<0.5\LLN,\>1.75\ULN; leukocytes(leu.),glucose\<0.6\LLN,\>1.5\ULN;lymphocytes(lym.), lym./leu.(%),neutrophils (neu.), neu./leu.(%), protein,albumin\<0.8\LLN,\>1.2\ULN;basophils(bas.), bas./leu.(%), eosinophils(eos.), eos./leu., monocytes(mon.), mon./leu.(%), urate\>1.2\ULN;bilirubin (total, direct,indirect)\>1.5\ULN;aspartate/alanine aminotransferase,gamma glutamyl transferase,lactate dehydrogenase,alkaline phosphatase\>3.0\ULN;urea nitrogen,creatinine,triglycerides, chl.\>1.3\ULN; sodium \<0.95\LLN,\>1.05\ULN; creatine kinase \>2.0\ULN;Urine: pH\<4.5,\>8;glucose, ketones,protein, HGB,urobilinogen,bilirubin,nitrite,leukocyte esterase\>=1;ery., leu.\>= 20;hyaline casts\>1;bacteria\>20.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAE) (Stage 3)	Up to Week 40	Adverse event (AE) was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. SAE was any untoward medical occurrence that at any dose resulted in any of following outcomes/deemed significant for any other reason: death; initial /prolonged inpatient hospitalization; life-threatening; persistent or significant disability/incapacity; congenital anomaly/birth defect and suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic. AEs included both serious (if occurred) and all non-serious adverse events. TEAEs are events between first dose of study drug and up to Week 40 that were absent before treatment or that worsened relative to pretreatment state.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With TEAEs and SAEs (Stage 1 and Stage 2)	Up to Week 28	AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. SAE was any untoward medical occurrence that at any dose resulted in any of following outcomes/deemed significant for any other reason: death; initial /prolonged inpatient hospitalization; life-threatening; persistent or significant disability/incapacity; congenital anomaly/birth defect and suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic. AEs included both serious (if occurred) and all non-serious adverse events. TEAEs are events between first dose of study drug and up to Week 28 that were absent before treatment or that worsened relative to pretreatment state.
Number of Participants With Clinically Significant Laboratory Abnormalities (Amended Stage 2)	Up to Week 40	HGB,hematocrit,ery.,HDL chl.\<0.8\LLN;ret., ret./ery. (%)\<0.5\LLN,\>1.5\ULN;EMC volume,EMC HGB,EMC HGB concentration,potassium,chloride,calcium,bicarbonate\<0.9\LLN,\>1.1\ULN;platelets\<0.5\LLN,\>1.75\ULN;leu.,glucose\<0.6\LLN,\>1.5\ULN;lym., lym./leu.(%), neu., neu./leu. (%), protein,albumin \<0.8\LLN,\>1.2\ULN;bas., bas./leu.(%), eos., eos./leu., mon., mon./leu.(%), urate \>1.2\ULN;bilirubin (total, direct, indirect)\>1.5\ULN;aspartate/alanine aminotransferase, gamma glutamyl transferase, lactate dehydrogenase, alkaline phosphatase\>3.0\ULN;urea nitrogen, creatinine, triglycerides, chl.\>1.3\ULN; sodium \<0.95\LLN,\>1.05\ULN; creatine kinase \>2.0\ULN;Urine: pH\<4.5,\>8;glucose, ketones, protein, HGB, urobilinogen,bilirubin,nitrite,leukocyte esterase\>=1;ery., leu.\>= 20;hyaline casts\>1;bacteria\>20. Clinical significance of laboratory parameters was determined at the investigator's discretion.
Number of Participants With ECG Abnormalities (Stage 1 and Stage 2)	Up to Week 28	ECG abnormalities criteria included: 1) QTc interval adjusted according to Fridericia formula (QTcF) (msec): \>450, \>480, \>500, increase from baseline \>=30, increase from baseline \>=60; 2) Pulse rate (PR) (msec): \>=300, change from baseline (Chg) \>=25% or 50%; 3) QT (msec): \>=500; 4) QRS (msec): \>=200, Chg \>=25% or 50%. Categories, with at least 1 participant having ECG abnormality in any of the reporting arms, were reported in this outcome measure.
Change From Baseline in CDASI Activity Score at All Scheduled Timepoints Through Week 12 (Stage 3)	Baseline, Week 1, Week 4, Week 8 and Week 12	The treatment effect was defined as the difference (mean change from baseline at Weeks 1, 4, 8,12 in the active treatment group minus the mean change from baseline at Weeks 1, 4, 8, 12 in the placebo group) in the mean change of CDASI activity score from baseline at scheduled timepoints. The score (range: 0-100) consists of the ES, GHS, PS and AS. ES (range: 0-90) was obtained by summing up scores for the total erythema (ER \[0-45\], redness of the skin or mucous membranes), scaling (SC \[0-30\], peeling of the skin) and erosion/ulceration (EU \[0-15\], presence of the deeper wound). Total ER, SC and EU scores were calculated as a sum of the contributions from 15 individual areas of the body. GHS characterizes papules (swellings) on hand and is a sum of the papule's characterization score (0-6) and ulceration score (0-1). PS (0-2) characterizes abnormalities around nails. The AS (0-1) characterizes hair loss. Higher scores indicate greater disease severity.
Number of Participants With TEAEs and SAEs (Amended Stage 2)	Up to Week 40	AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. SAE was any untoward medical occurrence that at any dose resulted in any of following outcomes/deemed significant for any other reason: death; initial /prolonged inpatient hospitalization; life-threatening; persistent or significant disability/incapacity; congenital anomaly/birth defect and suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic. AEs included both serious (if occurred) and all non-serious adverse events. TEAEs are events between first dose of study drug and up to Week 40 that were absent before treatment or that worsened relative to pretreatment state.
Number of Participants With Clinically Significant Laboratory Abnormalities (Stage 1 and Stage 2)	Up to Week 28	HGB,hematocrit,ery.,HDL chl.\<0.8\LLN;ret., ret./ery. (%)\<0.5\LLN,\>1.5\ULN;EMC volume,EMC HGB,EMC HGB concentration,potassium,chloride,calcium,bicarbonate\<0.9\LLN,\>1.1\ULN;platelets\<0.5\LLN,\>1.75\ULN;leu.,glucose\<0.6\LLN,\>1.5\ULN;lym., lym./leu.(%), neu., neu./leu. (%), protein,albumin \<0.8\LLN,\>1.2\ULN;bas., bas./leu.(%), eos., eos./leu., mon., mon./leu.(%), urate \>1.2\ULN;bilirubin (total, direct, indirect)\>1.5\ULN;aspartate/alanine aminotransferase, gamma glutamyl transferase, lactate dehydrogenase, alkaline phosphatase\>3.0\ULN;urea nitrogen, creatinine, triglycerides, chl.\>1.3\ULN; sodium \<0.95\LLN,\>1.05\ULN; creatine kinase \>2.0\ULN;Urine: pH\<4.5,\>8;glucose, ketones, protein, HGB, urobilinogen,bilirubin,nitrite,leukocyte esterase\>=1;ery., leu.\>= 20;hyaline casts\>1;bacteria\>20. Clinical significance of laboratory parameters was determined at the investigator's discretion.
Number of Participants With Vital Sign Abnormalities (Stage 1 and Stage 2)	Up to Week 28	Abnormality in vital signs: Sitting pulse rate \<40 bpm to \>120 bpm, sitting DBP \< 50 mmHg, sitting SBP \<90 mmHg.
Number of Participants With ECG Abnormalities (Amended Stage 2)	Up to Week 40	ECG abnormalities criteria included: 1) QTc interval adjusted according to Fridericia formula (QTcF) (msec): \>450, \>480, \>500, increase from baseline \>=30, increase from baseline \>=60; 2) Pulse rate (PR) (msec): \>=300, change from baseline (Chg) \>=25% or 50%; 3) QT (msec): \>=500; 4) QRS (msec): \>=200, Chg \>=25% or 50%. Categories, with at least 1 participant having ECG abnormality in any of the reporting arms, were reported in this outcome measure.
Change From Baseline in CDASI Activity Score at at All Scheduled Timepoints Through Week 12 (Stage 1, Stage 2 and Amended Stage 2)	Baseline, Week 1, Week 4, and Week 8 (except for Week 12 which is a primary outcome measure)	The treatment effect was defined as the difference (mean change from baseline at Weeks 1, 4, 8 in the active treatment group minus the mean change from baseline at Weeks 1, 4, 8 in the placebo group) in the mean change of CDASI activity score from baseline at scheduled timepoints. The score (range: 0-100) consists of the ES, GHS, PS and AS. ES (range: 0-90) was obtained by summing up scores for the total erythema (ER \[0-45\], redness of the skin or mucous membranes), scaling (SC \[0-30\], peeling of the skin) and erosion/ulceration (EU \[0-15\], presence of the deeper wound). Total ER, SC and EU scores were calculated as a sum of the contributions from 15 individual areas of the body. GHS characterizes papules (swellings) on hand and is a sum of the papule's characterization score (0-6) and ulceration score (0-1). PS (0-2) characterizes abnormalities around nails. The AS (0-1) characterizes hair loss. Higher scores indicate greater disease severity.
Absolute Values of CDASI Activity Score at All Scheduled Timepoints Through Week 12 (All Stages)	Baseline, Week 1, Week 4, Week 8 and Week 12	The CDASI activity score (range: 0-100) consists of the ES, GHS, PS and AS. ES (range: 0-90) was obtained by summing up scores for the total erythema (ER \[0-45\], redness of the skin or mucous membranes), scaling (SC \[0-30\], peeling of the skin) and erosion/ulceration (EU \[0-15\], presence of the deeper wound). Total ER, SC and EU scores were calculated as a sum of the contributions from 15 individual areas of the body. GHS characterizes papules (swellings) on hand and is a sum of the papule's characterization score (0-6) and ulceration score (0-1). PS (0-2) characterizes abnormalities around nails. The AS (0-1) characterizes hair loss. Higher scores indicate greater disease severity.
Change From Baseline in the Core Set Measures (CSM) of the TIS (Global Disease Activity [PhGA] and Extramuscular Global Assessment [EmGA]) (Stage 3)	Baseline, Week 4, Week 8 and Week 12	PhGA: assessment of the severity of disease by the physician. The physician used the visual analog scale and put a mark on 0 cm (best) -10 cm (worst) scale where higher score indicated worse status. EmGA: overall evaluation of disease activity in all extramuscular systems using visual analog scale 0 cm (best) -10 cm (worst) scale where higher score indicated worse status.
Absolute Values of CDASI Damage Score at All Scheduled Timepoints Through Week 12 (All Stages)	Baseline, Week 1, Week 4, Week 8 and Week 12	The Damage Score (DS) was calculated as a sum of the total poilkiloderma score (POLS), total calcinosis score (CALS) and Gotorn's hands damage score (GHDS). The POLS characterizes specific dispigmentation in the particulal area and calcinosis score characterizes calcification of the skin in the particular area. The POLS and the CALS are summed up over 15 individual areas in the body and each of them has range 0-15. The GHDS has the range 0-2 so that the DS has the range 0-32. Higher scores indicate greater disease severity.
Change From Baseline in the CSM of the TIS (PtGA) (Stage 3)	Baseline, Week 4, Week 8 and Week 12	PtGA: assessment of the severity of disease by the participant/participant's guardian, using a visual analog scale from 0 mm (no evidence of disease activity) to 100 mm (extremely active or severe disease activity). Higher score indicated worse status.
Change From Baseline in the CSM of the TIS (MMT8 and HAQ01-HAQ-DI) (Stage 3)	Week 4, Week 8 and Week 12	Manual Muscle Testing-8 designated muscle groups (MMT-8): was a set of 8 designated muscles tested unilaterally generally on right side (left side used unless right side cannot be used). Potential score range was from 0 to 80, where higher scores denoted better health status. HAQ-DI: contained eight sections (including dressing \& grooming, arising, eating, walking, hygiene, grip, reach, and activities). Each section had multiple questions that the participant used to rank their functionality and ranged from 0 to 3 where 0 = without any difficulty and 3 = unable to do. For each participant, the average ranking was calculated for each of the eight sections. HAQ-DI had a score range of 0 to 3, where higher score reflected worse status.
Absolute Values for Total Improvement Score (TIS) at Week 12 and Intermediate Scheduled Time Points (Stage 3)	Week 4, Week 8 and Week 12	The TIS was the sum of all 6 improvement scores where higher score indicates worse status (PhGA \[from the MDAAT, 0-20 scale\], PtGA \[0-10 scale\], MMT \[0-35 scale\], HAQ-DI \[0-10 scale\], muscle enzymes \[0-7.5 scale\], and extramuscular global assessment \[0-20 scale\]) associated with the change in each core set measure. A total improvement score between 0 and 100 corresponded to the degree of improvement, with higher scores corresponding to a greater degree of improvement: of ≥20 represented minimal improvement, a score of ≥40 represented moderate improvement, and a score of ≥60 represented major improvement.
Change From Baseline in the CSM of the TIS (Aldolase and Creatine Kinase) (Stage 3)	Baseline, Week 4, Week 8 and Week 12	The LS mean (with 90% CI) of CSM of the TIS (aldolase and creatine kinase) at weeks 4, 8, 12 were presented.
Number of Participants With Vital Sign Abnormalities (Amended Stage 2)	Up to Week 40	Abnormality in vital signs: Sitting pulse rate \<40 bpm to \>120 bpm, sitting DBP \< 50 mmHg, sitting SBP \<90 mmHg.

Trial Locations

Locations (40): Johns Hopkins Bayview Medical Center
🇺🇸
Baltimore, Maryland, United States
Brigham and Women's Hospital - CTH
🇺🇸
Boston, Massachusetts, United States
Brigham and Women's Hospital
🇺🇸
Boston, Massachusetts, United States
Cleveland Clinic Foundation
🇺🇸
Cleveland, Ohio, United States
Nova Reuma spolka partnerska
🇵🇱
Bialystok, Poland
The University of Kansas Medical Center
🇺🇸
Kansas City, Kansas, United States
KU Clinical Research Center - Clinical and Translational Science Unit (CTSU)
🇺🇸
Fairway, Kansas, United States
Oregon Health & Science University
🇺🇸
Portland, Oregon, United States
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
Mayo Clinic
🇺🇸
Scottsdale, Arizona, United States
Mayo Clinic Arizona Research Pharmacy
🇺🇸
Phoenix, Arizona, United States
University of Debrecen
🇭🇺
Debrecen, Hajdú-bihar, Hungary
OHSU, Center for Health and Healing CHH2
🇺🇸
Portland, Oregon, United States
Centrum Medyczne Plejady
🇵🇱
Krakow, Poland
Oregon Clinical & Translational Research Institute
🇺🇸
Portland, Oregon, United States
Mayo Clinic Florida
🇺🇸
Jacksonville, Florida, United States
University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
Brigham and Women's Hospital - CTC
🇺🇸
Boston, Massachusetts, United States
Attune Health Research Inc.
🇺🇸
Beverly Hills, California, United States
University Of Miami Hospital
🇺🇸
Miami, Florida, United States
Freidenrich Center for Translational Research at Stanford University
🇺🇸
Palo Alto, California, United States
The University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
University of Miami Hospital Clinical Translational Research Site (Infusion site)
🇺🇸
Miami, Florida, United States
Brigham and Women's Hospital - ACC
🇺🇸
Boston, Massachusetts, United States
Clinical Research Unit (CRU)
🇺🇸
Minneapolis, Minnesota, United States
Lillehei Clinical Research Unit (LCRU)
🇺🇸
Minneapolis, Minnesota, United States
University of Minnesota Health Rheumatology Clinic
🇺🇸
Minneapolis, Minnesota, United States
New York University School of Medicine
🇺🇸
New York, New York, United States
Department of Medicine Division of Rheumatic and Autoimmune Disease
🇺🇸
Minneapolis, Minnesota, United States
University of Minnesota, Department of Dermatology
🇺🇸
Minneapolis, Minnesota, United States
Center for Outpatient Health
🇺🇸
Saint Louis, Missouri, United States
NYU Langone Health Clinical Research Center
🇺🇸
New York, New York, United States
Mount Sinai Doctors Dermatology
🇺🇸
New York, New York, United States
University of Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States
University of Texas Southwestern Medical Center
🇺🇸
Dallas, Texas, United States
University of Utah MidValley Dermatology
🇺🇸
Murray, Utah, United States
Center for Clinical & Translational Science
🇺🇸
Salt Lake City, Utah, United States
Universitaetsklinikum Tuebingen
🇩🇪
Tuebingen, Germany
Hospital Quiron Infanta Luisa
🇪🇸
Sevilla, Spain
Hospital Universitario 12 de Octubre
🇪🇸
Madrid, Spain