Study Evaluating Efficacy and Safety of Octagam 10% in Patients With Dermatomyositis (Idiopathic Inflammatory Myopathy)

Octapharma95 enrolled

Overview

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Dermatomyositis

Interventions

Octagam 10%DRUG

Patients to be treated with Octagam 10%

PlaceboOTHER

Patients to be treated with a Placebo

Eligibility

Sex: ALLMin age: 18 YearsMax age: 79 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Subjects with diagnosis of definite or probable DM according to the Bohan and Peter criteria. 2. 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). 3. Subjects with active disease, assessed and agreed upon by an independent adjudication committee. 4. 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). 5. Males or females ≥ 18 to \< 80 years of age. 6. Voluntarily given, fully informed written consent obtained from subject before any study-related procedures are conducted. 7. Subject must be capable to understand and comply with the relevant aspects of the study protocol. Exclusion Criteria: 1. 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). 2. 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. 3. 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. 4. Subjects with immune-mediated necrotizing myopathy with absence of typical DM rash. 5. Subjects with generalized, severe musculoskeletal conditions other than DM that prevent a sufficient assessment of the subject by the physician. 6. Subjects who have received IgG treatment within the last 6 months before enrolment. 7. Subjects who received blood or plasma-derived products (other than IgG) or plasma exchange within the last 3 months before enrolment. 8. Subjects starting or planning to start a physical therapy-directed exercise regimen during the trial. 9. Cardiac insufficiency (New York Heart Association III/IV), cardiomyopathy, significant cardiac dysrhythmia requiring treatment, unstable or advanced ischemic heart disease. 10. Severe liver disease, with signs of ascites and hepatic encephalopathy. 11. Severe kidney disease (as defined by estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73 m2). 12. Known hepatitis B, hepatitis C or HIV infection. 13. 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. 14. Body mass index ≥40 kg/m2. 15. Medical conditions whose symptoms and effects could alter protein catabolism and/or IgG utilization (e.g. protein-losing enteropathies, nephrotic syndrome). 16. Known IgA deficiency with antibodies to IgA. 17. History of hypersensitivity, anaphylaxis or severe systemic response to immuno-globulin, blood or plasma derived products or any component of Octagam 10%. 18. Known blood hyperviscosity, or other hypercoagulable states. 19. Subjects with a history of drug abuse within the past 5 years prior to study enrollment. 20. Subjects unable or unwilling to understand or comply with the study protocol. 21. Participating in another interventional clinical study with investigational treatment within 3 months prior to study enrollment. 22. 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. 23. Subjects who are accommodated in an institution or care facility based on an official directive or court order. 24. Subjects who are in any way dependent on the Sponsor, Investigator or Study Site. 25. Subjects who received forbidden medication within the washout period as defined in Section 4.2.2 (Table 3).

Locations (37)

Outcomes

Primary Outcomes

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

Time frame: At week 16

Secondary Outcomes

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.

Time frame: 16 weeks

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.

Time frame: 40 weeks

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.

Data from ClinicalTrials.gov

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Octapharma Research Site

Huntington Beach, California, United States

Octapharma Research Site

Los Angeles, California, United States

University of California -Irvine

Orange, California, United States

Octapharma Research Site

Orlando, Florida, United States

NeuroMedical Research Center

Panama City, Florida, United States

Octapharma Research Site

Plantation, Florida, United States

University of South Florida

Tampa, Florida, United States

Octapharma Research Site

Kansas City, Kansas, United States

Octapharma Research Site

Ann Arbor, Michigan, United States

Octapharma Research Site

Rochester, Minnesota, United States

...and 27 more locations

Time frame: First 16 weeks

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.

Time frame: From week 16 to Week 40

Mean Change From Baseline (Week 0) to End of Extension Period (Week 40) in the Modified Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI)

Time frame: 40 weeks

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.