A Study looking at Investigational drug and Placebo administered to adult Patients with moderate to severe Dermatomyositis
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
75
A humanized immunoglobulin neutralizing antibody
Placebo contains histidine, sucrose, PS80, ethylene diamine, and triacetic acid
A humanized immunoglobulin neutralizing antibody
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.
Time frame: Baseline and Week 12
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.
Time frame: Up to Week 40
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.
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University of Alabama at Birmingham
Birmingham, Alabama, United States
The University of Alabama at Birmingham
Birmingham, Alabama, United States
The University of Alabama at Birmingham
Birmingham, Alabama, United States
Mayo Clinic Arizona Research Pharmacy
Phoenix, Arizona, United States
Mayo Clinic
Scottsdale, Arizona, United States
Attune Health Research Inc.
Beverly Hills, California, United States
Freidenrich Center for Translational Research at Stanford University
Palo Alto, California, United States
Mayo Clinic Florida
Jacksonville, Florida, United States
University Of Miami Hospital
Miami, Florida, United States
University of Miami Hospital Clinical Translational Research Site (Infusion site)
Miami, Florida, United States
...and 31 more locations
Time frame: Up to Week 40
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.
Time frame: Baseline up to Week 40
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.
Time frame: Baseline up to Week 40
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.
Time frame: Up to Week 28
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.
Time frame: Up to Week 40
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.
Time frame: Up to Week 28
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.
Time frame: Up to Week 40
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.
Time frame: Up to Week 28
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.
Time frame: Up to Week 40
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.
Time frame: Up to Week 28
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.
Time frame: Up to Week 40
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.
Time frame: Baseline, Week 1, Week 4, and Week 8 (except for Week 12 which is a primary outcome measure)
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.
Time frame: Baseline, Week 1, Week 4, Week 8 and Week 12
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.
Time frame: Baseline, Week 1, Week 4, Week 8 and Week 12
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.
Time frame: Baseline, Week 1, Week 4, Week 8 and Week 12
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.
Time frame: Week 4, Week 8 and Week 12
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.
Time frame: Baseline, Week 4, Week 8 and Week 12
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.
Time frame: Baseline, Week 4, Week 8 and Week 12
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.
Time frame: Week 4, Week 8 and Week 12
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.
Time frame: Baseline, Week 4, Week 8 and Week 12