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A Study In Adults With Moderate To Severe Dermatomyositis

Primary Purpose

Dermatomyositis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
PF-06823859 low
Placebo Arm
PF-06823859 high
Sponsored by
Pfizer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Dermatomyositis

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria for Patients with Skin Predominant Activity:

  • Must have CDASI Activity score of greater than or equal to 14, and have failed at least 1 standard of care systemic treatment, (eg, corticosteroids).

  • Confirmation of DM by the investigator and two of the following:

    1. Gottron's papules;
    2. Gottron's sign;
    3. Heliotrope eruption;
    4. Nailfold changes, (dilated capillary loops, capillary dropout, cuticular hypertrophy and/or rugged cuticles;
    5. Photodistributed violaceous erythema, (skin that is exposed to sunlight and appears purplish/reddish, and patchy in appearance;
    6. Positive DM serology -
  • Post DM diagnosis; standard of care workup for DM must have been completed prior to entry into this research study.
  • Willing to provide 8 biopsies during the course of the research study

Inclusion Criteria for Patients with Muscle Predominant Activity:

  • MMT-8 ≤136/150 and PhGA, VAS ≥3 cm (0-10 cm) by visual analog scale (VAS)

  • Sum of PhGA, VAS, PtGA, and extramuscular global assessment VAS scores is ≥10 cm (0-10 cm) VAS for each.

    • Participant has failed at least two or more adequate courses of an immunosuppressive agent or immunomodulatory agent, including IVIG, at a dose known to be effective for rheumatologic diseases.

Exclusion Criteria for Patients with Skin Predominant Activity:

  • Investigator site staff or members of their family.
  • Acute and Chronic present medical conditions
  • Intake of greater than 15 mg of prednisone or equivalent per day
  • Pregnant or breastfeeding females. Fertile men and women who will not comply with the use of 2 effective birth control methods as per the research protocol
  • Have required management of acute or chronic infections
  • Have pre existing demyelinating disorder such as multiple sclerosis, or other severe neurological deficits.
  • Clinically significant lab abnormalities
  • Any health condition that may be worsened by immunosuppression

Exclusion Criteria for Patients with Muscle Predominant Activity:

Similar to patients with skin predominant activity; Intake of >20 mg oral prednisone/day, or equivalent

Sites / Locations

  • University of Alabama at Birmingham
  • The University of Alabama at Birmingham
  • The University of Alabama at Birmingham
  • Mayo Clinic Arizona Research Pharmacy
  • Mayo Clinic
  • Attune Health Research Inc.
  • Freidenrich Center for Translational Research at Stanford University
  • Mayo Clinic Florida
  • University Of Miami Hospital
  • University of Miami Hospital Clinical Translational Research Site (Infusion site)
  • KU Clinical Research Center - Clinical and Translational Science Unit (CTSU)
  • The University of Kansas Medical Center
  • Johns Hopkins Bayview Medical Center
  • Brigham and Women's Hospital - ACC
  • Brigham and Women's Hospital - CTC
  • Brigham and Women's Hospital - CTH
  • Brigham and Women's Hospital
  • Clinical Research Unit (CRU)
  • Department of Medicine Division of Rheumatic and Autoimmune Disease
  • Lillehei Clinical Research Unit (LCRU)
  • University of Minnesota Health Rheumatology Clinic
  • University of Minnesota, Department of Dermatology
  • Center for Outpatient Health
  • Washington University School of Medicine
  • New York University School of Medicine
  • NYU Langone Health Clinical Research Center
  • Mount Sinai Doctors Dermatology
  • Cleveland Clinic Foundation
  • OHSU, Center for Health and Healing CHH2
  • Oregon Clinical & Translational Research Institute
  • Oregon Health & Science University
  • University of Pennsylvania
  • University of Texas Southwestern Medical Center
  • University of Utah MidValley Dermatology
  • Center for Clinical & Translational Science
  • Universitaetsklinikum Tuebingen
  • University of Debrecen
  • Nova Reuma spolka partnerska
  • Centrum Medyczne Plejady
  • Hospital Universitario 12 de Octubre
  • Hospital Quiron Infanta Luisa

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Experimental

Experimental

Arm Label

Placebo ARM

PF-06823859 ARM high

PF-06823859 ARM low

Arm Description

Outcomes

Primary Outcome Measures

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)
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 Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAE) (Stage 3)
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.
Number of Participants With Clinically Significant Laboratory Abnormalities (Stage 3)
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 Vital Sign Abnormalities (Stage 3)
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.
Number of Participants With Electrocardiogram (ECG) Abnormalities (Stage 3)
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.

Secondary Outcome Measures

Number of Participants With TEAEs and SAEs (Stage 1 and Stage 2)
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 TEAEs and SAEs (Amended Stage 2)
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)
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 Clinically Significant Laboratory Abnormalities (Amended Stage 2)
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)
Abnormality in vital signs: Sitting pulse rate <40 bpm to >120 bpm, sitting DBP < 50 mmHg, sitting SBP <90 mmHg.
Number of Participants With Vital Sign Abnormalities (Amended Stage 2)
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 (Stage 1 and Stage 2)
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 ECG Abnormalities (Amended Stage 2)
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)
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.
Change From Baseline in CDASI Activity Score at All Scheduled Timepoints Through Week 12 (Stage 3)
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.
Absolute Values of CDASI Activity Score at All Scheduled Timepoints Through Week 12 (All Stages)
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.
Absolute Values of CDASI Damage Score at All Scheduled Timepoints Through Week 12 (All Stages)
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.
Absolute Values for Total Improvement Score (TIS) at Week 12 and Intermediate Scheduled Time Points (Stage 3)
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 Core Set Measures (CSM) of the TIS (Global Disease Activity [PhGA] and Extramuscular Global Assessment [EmGA]) (Stage 3)
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.
Change From Baseline in the CSM of the TIS (PtGA) (Stage 3)
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)
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.
Change From Baseline in the CSM of the TIS (Aldolase and Creatine Kinase) (Stage 3)
The LS mean (with 90% CI) of CSM of the TIS (aldolase and creatine kinase) at weeks 4, 8, 12 were presented.

Full Information

First Posted
June 5, 2017
Last Updated
September 8, 2023
Sponsor
Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT03181893
Brief Title
A Study In Adults With Moderate To Severe Dermatomyositis
Official Title
A PHASE 2 DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED STUDY TO EVALUATE THE EFFICACY, SAFETY, AND TOLERABILITY OF PF-06823859 IN ADULT SUBJECTS WITH DERMATOMYOSITIS
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
January 23, 2018 (Actual)
Primary Completion Date
May 27, 2022 (Actual)
Study Completion Date
November 28, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dermatomyositis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
75 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo ARM
Arm Type
Placebo Comparator
Arm Title
PF-06823859 ARM high
Arm Type
Experimental
Arm Title
PF-06823859 ARM low
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
PF-06823859 low
Intervention Description
A humanized immunoglobulin neutralizing antibody
Intervention Type
Drug
Intervention Name(s)
Placebo Arm
Intervention Description
Placebo contains histidine, sucrose, PS80, ethylene diamine, and triacetic acid
Intervention Type
Drug
Intervention Name(s)
PF-06823859 high
Intervention Description
A humanized immunoglobulin neutralizing antibody
Primary Outcome Measure Information:
Title
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)
Description
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.
Time Frame
Baseline and Week 12
Title
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAE) (Stage 3)
Description
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.
Time Frame
Up to Week 40
Title
Number of Participants With Clinically Significant Laboratory Abnormalities (Stage 3)
Description
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.
Time Frame
Up to Week 40
Title
Number of Participants With Vital Sign Abnormalities (Stage 3)
Description
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.
Time Frame
Baseline up to Week 40
Title
Number of Participants With Electrocardiogram (ECG) Abnormalities (Stage 3)
Description
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.
Time Frame
Baseline up to Week 40
Secondary Outcome Measure Information:
Title
Number of Participants With TEAEs and SAEs (Stage 1 and Stage 2)
Description
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.
Time Frame
Up to Week 28
Title
Number of Participants With TEAEs and SAEs (Amended Stage 2)
Description
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.
Time Frame
Up to Week 40
Title
Number of Participants With Clinically Significant Laboratory Abnormalities (Stage 1 and Stage 2)
Description
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.
Time Frame
Up to Week 28
Title
Number of Participants With Clinically Significant Laboratory Abnormalities (Amended Stage 2)
Description
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.
Time Frame
Up to Week 40
Title
Number of Participants With Vital Sign Abnormalities (Stage 1 and Stage 2)
Description
Abnormality in vital signs: Sitting pulse rate <40 bpm to >120 bpm, sitting DBP < 50 mmHg, sitting SBP <90 mmHg.
Time Frame
Up to Week 28
Title
Number of Participants With Vital Sign Abnormalities (Amended Stage 2)
Description
Abnormality in vital signs: Sitting pulse rate <40 bpm to >120 bpm, sitting DBP < 50 mmHg, sitting SBP <90 mmHg.
Time Frame
Up to Week 40
Title
Number of Participants With ECG Abnormalities (Stage 1 and Stage 2)
Description
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.
Time Frame
Up to Week 28
Title
Number of Participants With ECG Abnormalities (Amended Stage 2)
Description
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.
Time Frame
Up to Week 40
Title
Change From Baseline in CDASI Activity Score at at All Scheduled Timepoints Through Week 12 (Stage 1, Stage 2 and Amended Stage 2)
Description
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.
Time Frame
Baseline, Week 1, Week 4, and Week 8 (except for Week 12 which is a primary outcome measure)
Title
Change From Baseline in CDASI Activity Score at All Scheduled Timepoints Through Week 12 (Stage 3)
Description
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.
Time Frame
Baseline, Week 1, Week 4, Week 8 and Week 12
Title
Absolute Values of CDASI Activity Score at All Scheduled Timepoints Through Week 12 (All Stages)
Description
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.
Time Frame
Baseline, Week 1, Week 4, Week 8 and Week 12
Title
Absolute Values of CDASI Damage Score at All Scheduled Timepoints Through Week 12 (All Stages)
Description
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.
Time Frame
Baseline, Week 1, Week 4, Week 8 and Week 12
Title
Absolute Values for Total Improvement Score (TIS) at Week 12 and Intermediate Scheduled Time Points (Stage 3)
Description
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.
Time Frame
Week 4, Week 8 and Week 12
Title
Change From Baseline in the Core Set Measures (CSM) of the TIS (Global Disease Activity [PhGA] and Extramuscular Global Assessment [EmGA]) (Stage 3)
Description
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.
Time Frame
Baseline, Week 4, Week 8 and Week 12
Title
Change From Baseline in the CSM of the TIS (PtGA) (Stage 3)
Description
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.
Time Frame
Baseline, Week 4, Week 8 and Week 12
Title
Change From Baseline in the CSM of the TIS (MMT8 and HAQ01-HAQ-DI) (Stage 3)
Description
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.
Time Frame
Week 4, Week 8 and Week 12
Title
Change From Baseline in the CSM of the TIS (Aldolase and Creatine Kinase) (Stage 3)
Description
The LS mean (with 90% CI) of CSM of the TIS (aldolase and creatine kinase) at weeks 4, 8, 12 were presented.
Time Frame
Baseline, Week 4, Week 8 and Week 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria for Patients with Skin Predominant Activity: Must have CDASI Activity score of greater than or equal to 14, and have failed at least 1 standard of care systemic treatment, (eg, corticosteroids). Confirmation of DM by the investigator and two of the following: Gottron's papules; Gottron's sign; Heliotrope eruption; Nailfold changes, (dilated capillary loops, capillary dropout, cuticular hypertrophy and/or rugged cuticles; Photodistributed violaceous erythema, (skin that is exposed to sunlight and appears purplish/reddish, and patchy in appearance; Positive DM serology - Post DM diagnosis; standard of care workup for DM must have been completed prior to entry into this research study. Willing to provide 8 biopsies during the course of the research study Inclusion Criteria for Patients with Muscle Predominant Activity: MMT-8 ≤136/150 and PhGA, VAS ≥3 cm (0-10 cm) by visual analog scale (VAS) Sum of PhGA, VAS, PtGA, and extramuscular global assessment VAS scores is ≥10 cm (0-10 cm) VAS for each. Participant has failed at least two or more adequate courses of an immunosuppressive agent or immunomodulatory agent, including IVIG, at a dose known to be effective for rheumatologic diseases. Exclusion Criteria for Patients with Skin Predominant Activity: Investigator site staff or members of their family. Acute and Chronic present medical conditions Intake of greater than 15 mg of prednisone or equivalent per day Pregnant or breastfeeding females. Fertile men and women who will not comply with the use of 2 effective birth control methods as per the research protocol Have required management of acute or chronic infections Have pre existing demyelinating disorder such as multiple sclerosis, or other severe neurological deficits. Clinically significant lab abnormalities Any health condition that may be worsened by immunosuppression Exclusion Criteria for Patients with Muscle Predominant Activity: Similar to patients with skin predominant activity; Intake of >20 mg oral prednisone/day, or equivalent
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
The University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35249
Country
United States
Facility Name
The University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Mayo Clinic Arizona Research Pharmacy
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
Facility Name
Mayo Clinic
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Facility Name
Attune Health Research Inc.
City
Beverly Hills
State/Province
California
ZIP/Postal Code
90211
Country
United States
Facility Name
Freidenrich Center for Translational Research at Stanford University
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
Mayo Clinic Florida
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
University Of Miami Hospital
City
Miami
State/Province
Florida
ZIP/Postal Code
33125
Country
United States
Facility Name
University of Miami Hospital Clinical Translational Research Site (Infusion site)
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
KU Clinical Research Center - Clinical and Translational Science Unit (CTSU)
City
Fairway
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Facility Name
The University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Johns Hopkins Bayview Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21224-6821
Country
United States
Facility Name
Brigham and Women's Hospital - ACC
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Brigham and Women's Hospital - CTC
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Brigham and Women's Hospital - CTH
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Clinical Research Unit (CRU)
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Department of Medicine Division of Rheumatic and Autoimmune Disease
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Lillehei Clinical Research Unit (LCRU)
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
University of Minnesota Health Rheumatology Clinic
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
University of Minnesota, Department of Dermatology
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Center for Outpatient Health
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63108
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
New York University School of Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
NYU Langone Health Clinical Research Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Mount Sinai Doctors Dermatology
City
New York
State/Province
New York
ZIP/Postal Code
10028
Country
United States
Facility Name
Cleveland Clinic Foundation
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
OHSU, Center for Health and Healing CHH2
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Oregon Clinical & Translational Research Institute
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390-9191
Country
United States
Facility Name
University of Utah MidValley Dermatology
City
Murray
State/Province
Utah
ZIP/Postal Code
84107
Country
United States
Facility Name
Center for Clinical & Translational Science
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84108
Country
United States
Facility Name
Universitaetsklinikum Tuebingen
City
Tuebingen
ZIP/Postal Code
72076
Country
Germany
Facility Name
University of Debrecen
City
Debrecen
State/Province
Hajdú-bihar
ZIP/Postal Code
H-4032
Country
Hungary
Facility Name
Nova Reuma spolka partnerska
City
Bialystok
ZIP/Postal Code
15-707
Country
Poland
Facility Name
Centrum Medyczne Plejady
City
Krakow
ZIP/Postal Code
30-363
Country
Poland
Facility Name
Hospital Universitario 12 de Octubre
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Hospital Quiron Infanta Luisa
City
Sevilla
ZIP/Postal Code
41010
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
IPD Sharing URL
https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Links:
URL
https://pmiform.com/clinical-trial-info-request?StudyID=C0251002
Description
To obtain contact information for a study center near you, click here.

Learn more about this trial

A Study In Adults With Moderate To Severe Dermatomyositis

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