Back to resultsStudy Evaluating Efficacy and Safety of Octagam 10% in Patients With Dermatomyositis (Idiopathic Inflammatory Myopathy) (IIM)
Primary Purpose
Dermatomyositis
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Octagam 10%
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Dermatomyositis focused on measuring DM
Eligibility Criteria
Inclusion Criteria:
- Subjects with diagnosis of definite or probable DM according to the Bohan and Peter criteria.
- Subjects under treatment with corticosteroids and/or maximally 2 immune-suppressants and being on stable therapy for at least 4 weeks (see Section 4.2.1) OR Subjects with previous failure of response or previous intolerance to corticosteroid and at least 1 additional immunosuppressive drug, and with steroid/immunosuppressive drugs washed out as per Section 4.2.1 (Table 2).
- Subjects with active disease, assessed and agreed upon by an independent adjudication committee.
- Manual Muscle Testing-8 (MMT-8) score <142, with at least 2 other abnormal Core Set Measures (CSM) (Visual Analogue Scale [VAS] of patient global activity ≥2 cm, physician's global disease activity ≥2 cm, extra-muscular activity ≥2 cm; at least one muscle enzyme >1.5 times upper limit of normal, Health Assessment Questionnaire ≥0.25).
- Males or females ≥ 18 to < 80 years of age.
- Voluntarily given, fully informed written consent obtained from subject before any study-related procedures are conducted.
- Subject must be capable to understand and comply with the relevant aspects of the study protocol.
Exclusion Criteria:
- Cancer-associated myositis, defined as the diagnosis of myositis within 2 years of the diagnosis of cancer (except basal or squamous cell skin cancer or carcinoma in situ of the cervix that has been excised and cured and at least 1 or 5 years, respectively, have passed since excision).
- Evidence of active malignant disease or malignancies diagnosed within the previous 5 years (including hematological malignancies and solid tumors) or breast cancer diagnosed within the previous 10 years.
- Subjects with overlap myositis (except for overlap with Sjögren's syndrome), connective tissue disease associated DM, inclusion body myositis, polymyositis, juvenile dermatomyositis or drug-induced myopathy.
- Subjects with immune-mediated necrotizing myopathy with absence of typical DM rash.
- Subjects with generalized, severe musculoskeletal conditions other than DM that prevent a sufficient assessment of the subject by the physician.
- Subjects who have received IgG treatment within the last 6 months before enrolment.
- Subjects who received blood or plasma-derived products (other than IgG) or plasma exchange within the last 3 months before enrolment.
- Subjects starting or planning to start a physical therapy-directed exercise regimen during the trial.
- Cardiac insufficiency (New York Heart Association III/IV), cardiomyopathy, significant cardiac dysrhythmia requiring treatment, unstable or advanced ischemic heart disease.
- Severe liver disease, with signs of ascites and hepatic encephalopathy.
- Severe kidney disease (as defined by estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2).
- Known hepatitis B, hepatitis C or HIV infection.
- Subjects with a history of TEE such as deep vein thrombosis, pulmonary embolism, myocardial infarction, ischemic stroke, transient ischemic attack, peripheral artery disease (Fontaine IV) ever.
- Body mass index ≥40 kg/m2.
- Medical conditions whose symptoms and effects could alter protein catabolism and/or IgG utilization (e.g. protein-losing enteropathies, nephrotic syndrome).
- Known IgA deficiency with antibodies to IgA.
- History of hypersensitivity, anaphylaxis or severe systemic response to immuno-globulin, blood or plasma derived products or any component of Octagam 10%.
- Known blood hyperviscosity, or other hypercoagulable states.
- Subjects with a history of drug abuse within the past 5 years prior to study enrollment.
- Subjects unable or unwilling to understand or comply with the study protocol.
- Participating in another interventional clinical study with investigational treatment within 3 months prior to study enrollment.
- Women who are breast feeding, pregnant, or planning to become pregnant, or are unwilling to apply an effective birth control method (such as implants, injectables, combined oral contraceptives, some intrauterine devices [IUDs], sexual abstinence or vasectomized partner) up to four weeks after the last IMP infusion.
- Subjects who are accommodated in an institution or care facility based on an official directive or court order.
- Subjects who are in any way dependent on the Sponsor, Investigator or Study Site.
- Subjects who received forbidden medication within the washout period as defined in Section 4.2.2 (Table 3).
Sites / Locations
- Octapharma Research Site
- Octapharma Research Site
- University of California -Irvine
- Octapharma Research Site
- NeuroMedical Research Center
- Octapharma Research Site
- University of South Florida
- Octapharma Research Site
- Octapharma Research Site
- Octapharma Research Site
- Octapharma Research Site
- Octapharma Research Site
- Octapharma Research Site
- Stones River Dermatology
- Austin Neuromuscular Center
- Octapharma Research Site
- Arthritis & Osteoporosis Clinic
- Octapharma Research Site
- Revmatologický ústav
- Charité-Universitätsmedizin Berlin, Klinik für Dermatologie, Venerologie und Allergologie
- Uniklinikum Münster, Klinik für Hautkrankheiten
- Semmelweis University Dermatology Clinic
- University of Debrecen Dept of Internal Medicine
- University of Szeged Dermatology Clinic
- Academic Medical Centre University of Amsterdam
- Centrum Medyczne Plejady
- Narodowy Instytut Geriatrii, Reumatologii I Rehabilitacji - Warsaw
- Octapharma Research Site
- Scientific Research Institute for Rheumatology (Moscow)
- I.M. Sechenov First Moscow State Medical University
- Orenburg State Medical University Based On Regional Clinical Hospital
- 3rd Rheumatology Department Of Clinical Rheumatology Hospital No. 25
- AVA-Peter clinic (Saint-Petersburg)
- Octapharma Research Site
- Octapharma Research Site
- Octapharma Research Site
- Octapharma Research Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Placebo
Octagam10%
Arm Description
Subjects randomized to placebo will receive 4 infusions of placebo every 4 weeks during the blinded First Period (16 weeks). If confirmed deterioration (deterioration at 2 consecutive visits) during the First Period, subjects will be switched to Octagam 10%. After response assessment at Week 16, all subjects with no confirmed deterioration and subjects switched to Octagam 10% due to confirmed deterioration but without further confirmed deterioration during the First Period will continue to receive 2.0 g/kg of Octagam 10% every 4 weeks during the subsequent 6-months open-label Extension Period. At Week 28, subjects who are stable on 2.0 g/kg Octagam 10% can be switched to 1.0 g/kg Octagam 10%, at the discretion of the investigator. Subjects randomized to placebo and switched to Octagam 10% due to confirmed deterioration, who deteriorate also during Octagam 10% treatment at 2 consecutive visits will drop-out after response assessment at Week 16 and will not enter the Extension Period.
Subjects randomized to Octagam will receive 4 infusions of 2.0 g/kg Octagam 10% every 4 weeks during the blinded First Period (16 weeks). If confirmed deterioration (deterioration at 2 consecutive visits) during the First Period, subjects will be switched to the alternate treatment. After response assessment at Week 16, all subjects with no confirmed deterioration during the First Period will continue receiving 2.0 g/kg of Octagam 10% every 4 weeks during the subsequent 6-months open-label Extension Period. At Week 28, subjects who are stable on 2.0 g/kg Octagam 10% can be switched to 1.0 g/kg Octagam 10%, at the discretion of the investigator. Subjects randomized to Octagam and switched to the alternate treatment due to confirmed deterioration will drop-out after response assessment at Week 16 and will not enter the Extension Period.
Outcomes
Primary Outcome Measures
Measure the Number of Patients Who Had an Increase of ≥20 Points on the Total Improvement Score (TIS)
Proportion of responders in the 2.0 g/kg Octagam 10% and placebo arms at Week 16 relative to baseline (Week 0). A responder being defined as a patient with an increase of ≥20 points on the Total Improvement Score (TIS, a scale from 0 to 100; 20-39 points being minimal improvement, 40-59 points being moderate improvement, and ≥60 points being major improvement
Secondary Outcome Measures
Proportion of TIS Responders by Improvement Category at Week 16
The TIS (Total Improvement Score) is a scale from 0 to 100 that allows for the discrimination between minimal, moderate and major responders depending on their improvement in the combined 6 CSM: ≥20 to 39 points being minimal improvement, ≥40 to 59 points being moderate improvement, and ≥60 points being major improvement.
Primary: Total number of all patients who had at least minimal, moderate, or major response.
At Least Moderate: Number of patients who had moderate or major response. At Least Major: Number of patients who had a major response.
Proportion of TIS Responders by Improvement Category at Week 40
The TIS (Total Improvement Score) is a scale from 0 to 100 that allows for the discrimination between minimal, moderate and major responders depending on their improvement in the combined 6 CSM: ≥20 to 39 points being minimal improvement, ≥40 to 59 points being moderate improvement, and ≥60 points being major improvement.
At Least Minimal: Total number of all patients who had minimal, moderate, or major response.
At Least Moderate: Number of patients who had moderate or major response. At Least Major: Number of patients who had a major response.
Mean Change From Baseline (Week 0) to End of First Period (Week 16) in the Modified Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI)
The modified CDASI has 3 activity measures (erythema, scale, and erosion/ulceration) and 2 damage measures (poikiloderma and calcinosis) which are assessed over 15 body areas. In addition, Gottron's papules on the hands are evaluated both for activity and damage. Lastly, the activity of periungual changes and alopecia is assessed.
Absence of skin lesions as described above is scored with "0" for each of the above described areas. Skin lesion will be scored with at least "1" (present), some lesions will be graded from "1" (less severe) to "2" (severe); others with "1", "2" or "3". For the total activity score as well as for the total damage score the sub-scores will be added up. The score for total activity ranges from 0 to 100, for total damage from 0 to 32 points. Higher scores indicate greater disease activity or greater disease damage respectively.
Mean Change From End of First Period (Week 16) to End of Extension Period (Week 40) in the Modified Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI)
The modified CDASI has 3 activity measures (erythema, scale, and erosion/ulceration) and 2 damage measures (poikiloderma and calcinosis) which are assessed over 15 body areas. In addition, Gottron's papules on the hands are evaluated both for activity and damage. Lastly, the activity of periungual changes and alopecia is assessed
Absence of skin lesions as described above is scored with "0" for each of the above described areas. Skin lesion will be scored with at least "1" (present), some lesions will be graded from "1" (less severe) to "2" (severe); others with "1", "2" or "3". For the total activity score as well as for the total damage score the sub-scores will be added up. The score for total activity ranges from 0 to 100, for total damage from 0 to 32 points. Higher scores indicate greater disease activity or greater disease damage respectively.
Mean Change From Baseline (Week 0) to End of Extension Period (Week 40) in the Modified Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI)
The modified CDASI has 3 activity measures (erythema, scale, and erosion/ulceration) and 2 damage measures (poikiloderma and calcinosis) which are assessed over 15 body areas. In addition, Gottron's papules on the hands are evaluated both for activity and damage. Lastly, the activity of periungual changes and alopecia is assessed.
Absence of skin lesions as described above is scored with "0" for each of the above described areas. Skin lesion will be scored with at least "1" (present), some lesions will be graded from "1" (less severe) to "2" (severe); others with "1", "2" or "3". For the total activity score as well as for the total damage score the sub-scores will be added up. The score for total activity ranges from 0 to 100, for total damage from 0 to 32 points. Higher scores indicate greater disease activity or greater disease damage respectively.
Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in: SF-36v2 Health Survey
The SF-36 is a multi-purpose, short-form health survey with only 36 questions. It yields an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures and a preference-based health utility index.
SF-36 scores ranging from 0 to 100. 0 represented the lowest possible score (worst health state) and 100 represented the highest possible score (best health state), with scores in between representing the percentages of the total possible score achieved by respondents on a given scale.
Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in Physician's Global Disease Activity
10 cm VAS assessing global disease activity from "No evidence of disease activity" to "Extremely active or severe disease activity"; Disease Activity being defined as potentially reversible pathology or physiology resulting from the myositis). Assessment completed by physician. 0 is lowest score and 10 is highest score. Higher score associated with worse outcome.
Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in: Patient Global Disease Activity
Patient's Global Disease Activity (10cm VAS assessing the overall activity of the patient's disease today from "No evidence of disease activity" to "Extremely active or severe disease activity", Disease Activity being active inflammation in the patient's muscles, skin, joints, intestines, heart, lungs or other parts of the body, which can improve when treated with medicines). 0 is lowest score and 10 is highest score. Higher score associated with worse outcome.
Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in: MMT-8
Manual Muscle Testing - MMT-8; a set of 8 designated muscles tested bilaterally [potential score 0 - 150]. Higher score associated with better outcome.
Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in: Health Assessment Questionnaire
Health Assessment Questionnaire (HAQ); a generic rather than a disease-specific instrument; comprised of 8 sections: dressing, arising, eating, walking, hygiene, reach, grip, and activities. There are 2 or 3 questions for each section. Scoring within each section is from 0 [without any difficulty] to 3 [unable to do]. For each section the score given to that section is the worst score within the section. The 8 scores of the 8 sections are summed and divided by 8). Assessment completed by patients. Lowest score 0 highest score 24. Higher score associated with worse outcome.
Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in Enzymes (Alanine Aminotransferase)
Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in Enzymes (Aspartate Aminotransferase)
Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in Enzymes (Lactate Dehydrogenase)
Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in Enzymes (Aldolase)
Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in Enzymes (Creatine Kinase)
Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in: Extra-muscular Activity
10 cm VAS assessing extra-muscular activity from "No evidence of disease activity" to "Extremely active or severe disease activity". It encompasses an overall evaluation for the disease activity in all the extramuscular organ systems and excludes muscle disease activity. Assessment completed by physician. 0 is lowest score and 10 is highest score. Higher score associated with worse outcome.
Mean TIS From Baseline (Week 0) to End of First Period (Week 16) and From Baseline (Week 0) to End of Extension Period (Week 40)
The TIS (Total Improvement Score) is a scale from 0 to 100 that allows for the discrimination between minimal, moderate and major responders depending on their improvement in the combined 6 CSM: ≥20 to 39 points being minimal improvement, ≥40 to 59 points being moderate improvement, and ≥60 points being major improvement.
Time to Minimal, Moderate and Major Improvement in TIS
When interpreting these time to event evaluations, one has to keep in mind that eventually all patients were treated with octagam 10%, so that differences in time to response for the Overall Period reflect this delayed start of treatment rather than the true difference between treatment with octagam 10% and placebo.
Time to Confirmed Deterioration in the First Period and Overall
Confirmed deterioration is defined as disease worsening on 2 consecutive visits. Worsening criteria are defined as either Physician's Global Disease Activity worsening ≥2cm and Manual Muscle Testing worsening ≥20% or Extra-muscular Activity worsening ≥2cm or any 3 of the following scores worsening by ≥30%: Physician's Global Disease Activity, Manual Muscle Test, Extra-muscular Activity, Patient's Global Disease Activity or Health Assessment Questionnaire.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02728752
Brief Title
Study Evaluating Efficacy and Safety of Octagam 10% in Patients With Dermatomyositis (Idiopathic Inflammatory Myopathy)
Acronym
IIM
Official Title
Prospective, Double-blind, Randomized, Placebo-Controlled Phase III Study Evaluating Efficacy and Safety of Octagam 10% in Patients With Dermatomyositis ("ProDERM Study")
Study Type
Interventional
2. Study Status
Record Verification Date
November 2021
Overall Recruitment Status
Completed
Study Start Date
February 27, 2017 (Actual)
Primary Completion Date
November 5, 2019 (Actual)
Study Completion Date
November 5, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Octapharma
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
Prospective, Double-blind, Randomized, Placebo-Controlled Phase III Study Evaluating Efficacy and Safety of Octagam 10% in Patients With Dermatomyositis ("ProDERM study")
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dermatomyositis
Keywords
DM
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
95 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Subjects randomized to placebo will receive 4 infusions of placebo every 4 weeks during the blinded First Period (16 weeks). If confirmed deterioration (deterioration at 2 consecutive visits) during the First Period, subjects will be switched to Octagam 10%. After response assessment at Week 16, all subjects with no confirmed deterioration and subjects switched to Octagam 10% due to confirmed deterioration but without further confirmed deterioration during the First Period will continue to receive 2.0 g/kg of Octagam 10% every 4 weeks during the subsequent 6-months open-label Extension Period. At Week 28, subjects who are stable on 2.0 g/kg Octagam 10% can be switched to 1.0 g/kg Octagam 10%, at the discretion of the investigator. Subjects randomized to placebo and switched to Octagam 10% due to confirmed deterioration, who deteriorate also during Octagam 10% treatment at 2 consecutive visits will drop-out after response assessment at Week 16 and will not enter the Extension Period.
Arm Title
Octagam10%
Arm Type
Experimental
Arm Description
Subjects randomized to Octagam will receive 4 infusions of 2.0 g/kg Octagam 10% every 4 weeks during the blinded First Period (16 weeks). If confirmed deterioration (deterioration at 2 consecutive visits) during the First Period, subjects will be switched to the alternate treatment. After response assessment at Week 16, all subjects with no confirmed deterioration during the First Period will continue receiving 2.0 g/kg of Octagam 10% every 4 weeks during the subsequent 6-months open-label Extension Period. At Week 28, subjects who are stable on 2.0 g/kg Octagam 10% can be switched to 1.0 g/kg Octagam 10%, at the discretion of the investigator. Subjects randomized to Octagam and switched to the alternate treatment due to confirmed deterioration will drop-out after response assessment at Week 16 and will not enter the Extension Period.
Intervention Type
Drug
Intervention Name(s)
Octagam 10%
Intervention Description
Patients to be treated with Octagam 10%
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Patients to be treated with a Placebo
Primary Outcome Measure Information:
Title
Measure the Number of Patients Who Had an Increase of ≥20 Points on the Total Improvement Score (TIS)
Description
Proportion of responders in the 2.0 g/kg Octagam 10% and placebo arms at Week 16 relative to baseline (Week 0). A responder being defined as a patient with an increase of ≥20 points on the Total Improvement Score (TIS, a scale from 0 to 100; 20-39 points being minimal improvement, 40-59 points being moderate improvement, and ≥60 points being major improvement
Time Frame
At week 16
Secondary Outcome Measure Information:
Title
Proportion of TIS Responders by Improvement Category at Week 16
Description
The TIS (Total Improvement Score) is a scale from 0 to 100 that allows for the discrimination between minimal, moderate and major responders depending on their improvement in the combined 6 CSM: ≥20 to 39 points being minimal improvement, ≥40 to 59 points being moderate improvement, and ≥60 points being major improvement.
Primary: Total number of all patients who had at least minimal, moderate, or major response.
At Least Moderate: Number of patients who had moderate or major response. At Least Major: Number of patients who had a major response.
Time Frame
16 weeks
Title
Proportion of TIS Responders by Improvement Category at Week 40
Description
The TIS (Total Improvement Score) is a scale from 0 to 100 that allows for the discrimination between minimal, moderate and major responders depending on their improvement in the combined 6 CSM: ≥20 to 39 points being minimal improvement, ≥40 to 59 points being moderate improvement, and ≥60 points being major improvement.
At Least Minimal: Total number of all patients who had minimal, moderate, or major response.
At Least Moderate: Number of patients who had moderate or major response. At Least Major: Number of patients who had a major response.
Time Frame
40 weeks
Title
Mean Change From Baseline (Week 0) to End of First Period (Week 16) in the Modified Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI)
Description
The modified CDASI has 3 activity measures (erythema, scale, and erosion/ulceration) and 2 damage measures (poikiloderma and calcinosis) which are assessed over 15 body areas. In addition, Gottron's papules on the hands are evaluated both for activity and damage. Lastly, the activity of periungual changes and alopecia is assessed.
Absence of skin lesions as described above is scored with "0" for each of the above described areas. Skin lesion will be scored with at least "1" (present), some lesions will be graded from "1" (less severe) to "2" (severe); others with "1", "2" or "3". For the total activity score as well as for the total damage score the sub-scores will be added up. The score for total activity ranges from 0 to 100, for total damage from 0 to 32 points. Higher scores indicate greater disease activity or greater disease damage respectively.
Time Frame
First 16 weeks
Title
Mean Change From End of First Period (Week 16) to End of Extension Period (Week 40) in the Modified Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI)
Description
The modified CDASI has 3 activity measures (erythema, scale, and erosion/ulceration) and 2 damage measures (poikiloderma and calcinosis) which are assessed over 15 body areas. In addition, Gottron's papules on the hands are evaluated both for activity and damage. Lastly, the activity of periungual changes and alopecia is assessed
Absence of skin lesions as described above is scored with "0" for each of the above described areas. Skin lesion will be scored with at least "1" (present), some lesions will be graded from "1" (less severe) to "2" (severe); others with "1", "2" or "3". For the total activity score as well as for the total damage score the sub-scores will be added up. The score for total activity ranges from 0 to 100, for total damage from 0 to 32 points. Higher scores indicate greater disease activity or greater disease damage respectively.
Time Frame
From week 16 to Week 40
Title
Mean Change From Baseline (Week 0) to End of Extension Period (Week 40) in the Modified Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI)
Description
The modified CDASI has 3 activity measures (erythema, scale, and erosion/ulceration) and 2 damage measures (poikiloderma and calcinosis) which are assessed over 15 body areas. In addition, Gottron's papules on the hands are evaluated both for activity and damage. Lastly, the activity of periungual changes and alopecia is assessed.
Absence of skin lesions as described above is scored with "0" for each of the above described areas. Skin lesion will be scored with at least "1" (present), some lesions will be graded from "1" (less severe) to "2" (severe); others with "1", "2" or "3". For the total activity score as well as for the total damage score the sub-scores will be added up. The score for total activity ranges from 0 to 100, for total damage from 0 to 32 points. Higher scores indicate greater disease activity or greater disease damage respectively.
Time Frame
40 weeks
Title
Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in: SF-36v2 Health Survey
Description
The SF-36 is a multi-purpose, short-form health survey with only 36 questions. It yields an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures and a preference-based health utility index.
SF-36 scores ranging from 0 to 100. 0 represented the lowest possible score (worst health state) and 100 represented the highest possible score (best health state), with scores in between representing the percentages of the total possible score achieved by respondents on a given scale.
Time Frame
From start of the trial till Week 40
Title
Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in Physician's Global Disease Activity
Description
10 cm VAS assessing global disease activity from "No evidence of disease activity" to "Extremely active or severe disease activity"; Disease Activity being defined as potentially reversible pathology or physiology resulting from the myositis). Assessment completed by physician. 0 is lowest score and 10 is highest score. Higher score associated with worse outcome.
Time Frame
From start of the trial till Week 40
Title
Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in: Patient Global Disease Activity
Description
Patient's Global Disease Activity (10cm VAS assessing the overall activity of the patient's disease today from "No evidence of disease activity" to "Extremely active or severe disease activity", Disease Activity being active inflammation in the patient's muscles, skin, joints, intestines, heart, lungs or other parts of the body, which can improve when treated with medicines). 0 is lowest score and 10 is highest score. Higher score associated with worse outcome.
Time Frame
From start of the trial till Week 40
Title
Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in: MMT-8
Description
Manual Muscle Testing - MMT-8; a set of 8 designated muscles tested bilaterally [potential score 0 - 150]. Higher score associated with better outcome.
Time Frame
From start of the trial till Week 40
Title
Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in: Health Assessment Questionnaire
Description
Health Assessment Questionnaire (HAQ); a generic rather than a disease-specific instrument; comprised of 8 sections: dressing, arising, eating, walking, hygiene, reach, grip, and activities. There are 2 or 3 questions for each section. Scoring within each section is from 0 [without any difficulty] to 3 [unable to do]. For each section the score given to that section is the worst score within the section. The 8 scores of the 8 sections are summed and divided by 8). Assessment completed by patients. Lowest score 0 highest score 24. Higher score associated with worse outcome.
Time Frame
From start of the trial till Week 40
Title
Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in Enzymes (Alanine Aminotransferase)
Time Frame
From start of the trial till Week 40
Title
Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in Enzymes (Aspartate Aminotransferase)
Time Frame
From start of the trial till Week 40
Title
Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in Enzymes (Lactate Dehydrogenase)
Time Frame
From start of the trial till Week 40
Title
Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in Enzymes (Aldolase)
Time Frame
From start of the trial till Week 40
Title
Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in Enzymes (Creatine Kinase)
Time Frame
From start of the trial till Week 40
Title
Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in: Extra-muscular Activity
Description
10 cm VAS assessing extra-muscular activity from "No evidence of disease activity" to "Extremely active or severe disease activity". It encompasses an overall evaluation for the disease activity in all the extramuscular organ systems and excludes muscle disease activity. Assessment completed by physician. 0 is lowest score and 10 is highest score. Higher score associated with worse outcome.
Time Frame
From start of the trial until Week 40
Title
Mean TIS From Baseline (Week 0) to End of First Period (Week 16) and From Baseline (Week 0) to End of Extension Period (Week 40)
Description
The TIS (Total Improvement Score) is a scale from 0 to 100 that allows for the discrimination between minimal, moderate and major responders depending on their improvement in the combined 6 CSM: ≥20 to 39 points being minimal improvement, ≥40 to 59 points being moderate improvement, and ≥60 points being major improvement.
Time Frame
Up to 40 weeks
Title
Time to Minimal, Moderate and Major Improvement in TIS
Description
When interpreting these time to event evaluations, one has to keep in mind that eventually all patients were treated with octagam 10%, so that differences in time to response for the Overall Period reflect this delayed start of treatment rather than the true difference between treatment with octagam 10% and placebo.
Time Frame
Up to 40 weeks
Title
Time to Confirmed Deterioration in the First Period and Overall
Description
Confirmed deterioration is defined as disease worsening on 2 consecutive visits. Worsening criteria are defined as either Physician's Global Disease Activity worsening ≥2cm and Manual Muscle Testing worsening ≥20% or Extra-muscular Activity worsening ≥2cm or any 3 of the following scores worsening by ≥30%: Physician's Global Disease Activity, Manual Muscle Test, Extra-muscular Activity, Patient's Global Disease Activity or Health Assessment Questionnaire.
Time Frame
Up to 40 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subjects with diagnosis of definite or probable DM according to the Bohan and Peter criteria.
Subjects under treatment with corticosteroids and/or maximally 2 immune-suppressants and being on stable therapy for at least 4 weeks (see Section 4.2.1) OR Subjects with previous failure of response or previous intolerance to corticosteroid and at least 1 additional immunosuppressive drug, and with steroid/immunosuppressive drugs washed out as per Section 4.2.1 (Table 2).
Subjects with active disease, assessed and agreed upon by an independent adjudication committee.
Manual Muscle Testing-8 (MMT-8) score <142, with at least 2 other abnormal Core Set Measures (CSM) (Visual Analogue Scale [VAS] of patient global activity ≥2 cm, physician's global disease activity ≥2 cm, extra-muscular activity ≥2 cm; at least one muscle enzyme >1.5 times upper limit of normal, Health Assessment Questionnaire ≥0.25).
Males or females ≥ 18 to < 80 years of age.
Voluntarily given, fully informed written consent obtained from subject before any study-related procedures are conducted.
Subject must be capable to understand and comply with the relevant aspects of the study protocol.
Exclusion Criteria:
Cancer-associated myositis, defined as the diagnosis of myositis within 2 years of the diagnosis of cancer (except basal or squamous cell skin cancer or carcinoma in situ of the cervix that has been excised and cured and at least 1 or 5 years, respectively, have passed since excision).
Evidence of active malignant disease or malignancies diagnosed within the previous 5 years (including hematological malignancies and solid tumors) or breast cancer diagnosed within the previous 10 years.
Subjects with overlap myositis (except for overlap with Sjögren's syndrome), connective tissue disease associated DM, inclusion body myositis, polymyositis, juvenile dermatomyositis or drug-induced myopathy.
Subjects with immune-mediated necrotizing myopathy with absence of typical DM rash.
Subjects with generalized, severe musculoskeletal conditions other than DM that prevent a sufficient assessment of the subject by the physician.
Subjects who have received IgG treatment within the last 6 months before enrolment.
Subjects who received blood or plasma-derived products (other than IgG) or plasma exchange within the last 3 months before enrolment.
Subjects starting or planning to start a physical therapy-directed exercise regimen during the trial.
Cardiac insufficiency (New York Heart Association III/IV), cardiomyopathy, significant cardiac dysrhythmia requiring treatment, unstable or advanced ischemic heart disease.
Severe liver disease, with signs of ascites and hepatic encephalopathy.
Severe kidney disease (as defined by estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2).
Known hepatitis B, hepatitis C or HIV infection.
Subjects with a history of TEE such as deep vein thrombosis, pulmonary embolism, myocardial infarction, ischemic stroke, transient ischemic attack, peripheral artery disease (Fontaine IV) ever.
Body mass index ≥40 kg/m2.
Medical conditions whose symptoms and effects could alter protein catabolism and/or IgG utilization (e.g. protein-losing enteropathies, nephrotic syndrome).
Known IgA deficiency with antibodies to IgA.
History of hypersensitivity, anaphylaxis or severe systemic response to immuno-globulin, blood or plasma derived products or any component of Octagam 10%.
Known blood hyperviscosity, or other hypercoagulable states.
Subjects with a history of drug abuse within the past 5 years prior to study enrollment.
Subjects unable or unwilling to understand or comply with the study protocol.
Participating in another interventional clinical study with investigational treatment within 3 months prior to study enrollment.
Women who are breast feeding, pregnant, or planning to become pregnant, or are unwilling to apply an effective birth control method (such as implants, injectables, combined oral contraceptives, some intrauterine devices [IUDs], sexual abstinence or vasectomized partner) up to four weeks after the last IMP infusion.
Subjects who are accommodated in an institution or care facility based on an official directive or court order.
Subjects who are in any way dependent on the Sponsor, Investigator or Study Site.
Subjects who received forbidden medication within the washout period as defined in Section 4.2.2 (Table 3).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wolfgang Frenzel
Organizational Affiliation
International Medical Director
Official's Role
Study Director
Facility Information:
Facility Name
Octapharma Research Site
City
Huntington Beach
State/Province
California
ZIP/Postal Code
92647
Country
United States
Facility Name
Octapharma Research Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
University of California -Irvine
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Octapharma Research Site
City
Orlando
State/Province
Florida
ZIP/Postal Code
32819
Country
United States
Facility Name
NeuroMedical Research Center
City
Panama City
State/Province
Florida
ZIP/Postal Code
32405
Country
United States
Facility Name
Octapharma Research Site
City
Plantation
State/Province
Florida
ZIP/Postal Code
33324
Country
United States
Facility Name
University of South Florida
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Octapharma Research Site
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Octapharma Research Site
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Octapharma Research Site
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Octapharma Research Site
City
Great Neck
State/Province
New York
ZIP/Postal Code
11021
Country
United States
Facility Name
Octapharma Research Site
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Octapharma Research Site
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Stones River Dermatology
City
Murfreesboro
State/Province
Tennessee
ZIP/Postal Code
37130
Country
United States
Facility Name
Austin Neuromuscular Center
City
Austin
State/Province
Texas
ZIP/Postal Code
78756
Country
United States
Facility Name
Octapharma Research Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77034
Country
United States
Facility Name
Arthritis & Osteoporosis Clinic
City
Waco
State/Province
Texas
ZIP/Postal Code
76710
Country
United States
Facility Name
Octapharma Research Site
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H3T 1E2
Country
Canada
Facility Name
Revmatologický ústav
City
Praha
ZIP/Postal Code
128 50
Country
Czechia
Facility Name
Charité-Universitätsmedizin Berlin, Klinik für Dermatologie, Venerologie und Allergologie
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
Uniklinikum Münster, Klinik für Hautkrankheiten
City
Münster
ZIP/Postal Code
48149
Country
Germany
Facility Name
Semmelweis University Dermatology Clinic
City
Budapest
ZIP/Postal Code
H-1085
Country
Hungary
Facility Name
University of Debrecen Dept of Internal Medicine
City
Debrecen
ZIP/Postal Code
H-4032
Country
Hungary
Facility Name
University of Szeged Dermatology Clinic
City
Szeged
ZIP/Postal Code
H-6720
Country
Hungary
Facility Name
Academic Medical Centre University of Amsterdam
City
Amsterdam
ZIP/Postal Code
1105AZ
Country
Netherlands
Facility Name
Centrum Medyczne Plejady
City
Kraków
ZIP/Postal Code
30-363
Country
Poland
Facility Name
Narodowy Instytut Geriatrii, Reumatologii I Rehabilitacji - Warsaw
City
Warsaw
ZIP/Postal Code
02-637
Country
Poland
Facility Name
Octapharma Research Site
City
Cluj-Napoca
ZIP/Postal Code
400006
Country
Romania
Facility Name
Scientific Research Institute for Rheumatology (Moscow)
City
Moscow
ZIP/Postal Code
115522
Country
Russian Federation
Facility Name
I.M. Sechenov First Moscow State Medical University
City
Moscow
ZIP/Postal Code
119435
Country
Russian Federation
Facility Name
Orenburg State Medical University Based On Regional Clinical Hospital
City
Orenburg
ZIP/Postal Code
460018
Country
Russian Federation
Facility Name
3rd Rheumatology Department Of Clinical Rheumatology Hospital No. 25
City
Saint Petersburg
ZIP/Postal Code
190068
Country
Russian Federation
Facility Name
AVA-Peter clinic (Saint-Petersburg)
City
Saint Petersburg
ZIP/Postal Code
191028
Country
Russian Federation
Facility Name
Octapharma Research Site
City
Ivano-Frankivs'k
ZIP/Postal Code
76018
Country
Ukraine
Facility Name
Octapharma Research Site
City
Lviv
ZIP/Postal Code
79000
Country
Ukraine
Facility Name
Octapharma Research Site
City
Sumy
ZIP/Postal Code
40022
Country
Ukraine
Facility Name
Octapharma Research Site
City
Ternopil'
ZIP/Postal Code
46002
Country
Ukraine
12. IPD Sharing Statement
Citations:
PubMed Identifier
36198179
Citation
Aggarwal R, Charles-Schoeman C, Schessl J, Bata-Csorgo Z, Dimachkie MM, Griger Z, Moiseev S, Oddis C, Schiopu E, Vencovsky J, Beckmann I, Clodi E, Bugrova O, Danko K, Ernste F, Goyal NA, Heuer M, Hudson M, Hussain YM, Karam C, Magnolo N, Nelson R, Pozur N, Prystupa L, Sardy M, Valenzuela G, van der Kooi AJ, Vu T, Worm M, Levine T; ProDERM Trial Group. Trial of Intravenous Immune Globulin in Dermatomyositis. N Engl J Med. 2022 Oct 6;387(14):1264-1278. doi: 10.1056/NEJMoa2117912.
Results Reference
derived
PubMed Identifier
33429735
Citation
Aggarwal R, Charles-Schoeman C, Schessl J, Dimachkie MM, Beckmann I, Levine T. Prospective, double-blind, randomized, placebo-controlled phase III study evaluating efficacy and safety of octagam 10% in patients with dermatomyositis ("ProDERM Study"). Medicine (Baltimore). 2021 Jan 8;100(1):e23677. doi: 10.1097/MD.0000000000023677.
Results Reference
derived
Learn more about this trial
Study Evaluating Efficacy and Safety of Octagam 10% in Patients With Dermatomyositis (Idiopathic Inflammatory Myopathy)
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