Study Evaluating Efficacy and Safety of Octanorm in Patients With Dermatomyositis

Phase 3TerminatedNCT03686969

Octapharma1 enrolled

Overview

DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED PHASE III STUDY EVALUATING EFFICACY AND SAFETY OF SUBCUTANEOUS HUMAN IMMUNOGLOBULIN (OCTANORM) IN PATIENTS WITH DERMATOMYOSITIS

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Dermatomyositis

Interventions

OctanormDRUG

Octanorm 0.5g/kg/week

PlaceboOTHER

Placebo

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 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 who have responded to IGIV treatment as assessed by the treating physician and being on a stable dose for at least 3 months on 2 g/kg bodyweight (+/- 10%). 3. For subjects being on other medication(s) for the treatment of DM (immunosuppressants, corticosteroids): a) subject was on such medication(s) at the start of IGIV treatment in the first place, and b) received such medication(s) for at least 3 months prior to study enrolment and at a stable dose for at least 4 weeks prior to study enrolment at the maximally allowed conditions as per Table 2 (see section 4.2.1). 4. MMT-8 score ≥144, with at least 3 other CSM to be normal or near normal as per the following criteria: Visual Analogue Scale \[VAS\] of patient global disease activity ≤2 cm, physician's global disease activity ≤2 cm, extra-muscular disease activity ≤2 cm; no muscle enzyme \>4 times upper limit of normal due to myositis, Health Assessment Questionnaire \[HAQ\] ≤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 and willing 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. Subjects \>5 years (\>10 years for breast cancer) of cancer diagnosis who have been treated and are in remission are allowed. 3. Subjects with overlap myositis (except for overlap with Sjögren's syndrome), connective tissue disease associated DM, inclusion body myositis, polymyositis 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 received blood or plasma-derived products (other than IGIV) or plasma exchange within the last 3 months before enrolment. 7. Subjects with administration of permitted concomitant medications exceeding the maximally allowed conditions as per section 4.2.1. 8. Subjects with administration of forbidden concomitant medications within the washout periods as defined in Table 3: see section 4.2.2. 9. Subjects starting or planning to start a physical therapy-directed exercise regimen during the trial. Subjects on stable physical therapy for \>4 weeks are allowed but the regimen should remain the same throughout the trial. 10. Cardiac insufficiency (New York Heart Association III/IV), cardiomyopathy, significant cardiac dysrhythmia requiring treatment, unstable or advanced ischemic heart disease. 11. Severe liver disease, with signs of ascites and hepatic encephalopathy. 12. Severe kidney disease (as defined by estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73 m2). 13. Known hepatitis B, hepatitis C or HIV infection. 14. Subjects with a history of deep vein thrombosis within the last year prior to study enrolment or pulmonary embolism ever. 15. Body mass index \>40 kg/m2 and/or body weight \>120 kg. 16. Medical conditions whose symptoms and effects could alter protein catabolism and/or IgG utilization (e.g. protein-losing enteropathies, nephrotic syndrome). 17. Known IgA deficiency with antibodies to IgA. 18. History of hypersensitivity, anaphylaxis or severe systemic response to immunoglobulin, blood or plasma derived products or any component of octanorm 16.5% such as polysorbate 80 or to sodium chloride. 19. Known blood hyperviscosity, or other hypercoagulable states. 20. Subjects with a history of drug abuse within the past 5 years prior to study enrolment. 21. Participating in another interventional clinical study with investigational treatment within 3 months prior to study enrolment. Subjects who participated in the Octagam 10% Dermatomyositis Study (GAM10-08) can be included. 22. Women who are breast feeding, pregnant, or planning to become pregnant, or are unwilling to apply an effective birth control method (as per protocol section 7.3.9 b) up to four weeks after the last IMP infusion received.

Locations (1)

I.M. SECHENOV FIRST MOSCOW STATE MEDICAL UNIVERSITY Rheumatology Department Of, Clinici Of Nephrology

Moscow, Russia

Outcomes

Primary Outcomes

MMT-8

MMT-8; a set of 8 designated muscles tested bilaterally \[potential score 0 - 150\]

Time frame: 32 weeks

CDASI

The CDASI is a clinician-scored single page instrument that separately measures activity and damage in the skin of DM patients for use in clinical practice or clinical/therapeutic studies.

Time frame: 32 weeks

Physician's Global Disease Activity VAS Worsening

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).

Time frame: 32 weeks

Secondary Outcomes

Extra-Muscular Disease Activity

Extra-muscular activity (part of MDAAT; a combined tool that captures the physician's assessment of disease activity of various organ systems using a scale from 0 = "Not present in the last 4 weeks" to 4 = "New - in the last 4 weeks \[compared to the previous 4 weeks\]" and a VAS).

Time frame: 32 weeks

Muscle Enzymes - Aldolase

Measurement of aldolase in blood

Time frame: 32 weeks

Muscle Enzymes - Creatine Kinase

Measurement of creatine kinase in blood

Time frame: 32 weeks

Muscle Enzymes - Alanine Aminotransferase

Measurement of alanine aminotransferase in blood

Time frame: 32 weeks

Data from ClinicalTrials.gov

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Muscle Enzymes - Aspartate Aminotransferase

Measurement of aspartate aminotransferase in blood

Time frame: 32 weeks

Muscle Enzymes - Lactate Dehydrogenase

Measurement of lactate dehydrogenase in blood

Time frame: 32 weeks

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).

Time frame: 32 weeks

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.

Time frame: 32 weeks

Mean Change in TIS

Total Improvement Score

Time frame: 32 weeks

Time to Clinically Important Deterioration

Time to clinically important deterioration

Time frame: 32 weeks

Adverse Events

Occurrence of all adverse events

Time frame: 32 weeks

TEEs

Monitoring safety with occurrence of all thromboembolic events (TEEs)

Time frame: 32 weeks

HTRs

Monitoring safety with occurrence of all hemolytic transfusion reactions (HTRs)

Time frame: 32 weeks

Injection Site Reactions

Monitoring safety by assessing local injection site reactions

Time frame: 32 weeks

Blood Pressure

Monitoring safety through blood pressure values

Time frame: 32 weeks

Heart Rate

Monitoring safety through heart rate values

Time frame: 32 weeks

Body Temperature

Monitoring safety through body temperature values

Time frame: 32 weeks

Respiratory Rate

Monitoring safety through respiratory rate values

Time frame: 32 weeks

Physical Examination

The physical examination outcome will be analyzed based on changes from baseline as adverse events.

Time frame: 32 Weeks

Sodium

Monitoring safety through lab sodium levels

Time frame: 32 weeks

Potassium

Monitoring safety through lab potassium levels

Time frame: 32 weeks

Glucose

Monitoring safety through lab glucose levels

Time frame: 32 weeks

ALAT

Monitoring safety through lab ALAT levels

Time frame: 32 weeks

ASAT

Monitoring safety through lab ASAT levels

Time frame: 32 weeks

LDH

Monitoring safety through lab LDH levels

Time frame: 32 weeks

Total Bilirubin

Monitoring safety through lab total bilirubin levels

Time frame: 32 weeks

Blood Urea Nitrogen

Monitoring safety through lab blood urea nitrogen levels

Time frame: 32 weeks

Urea

Monitoring safety through lab urea levels

Time frame: 32 weeks

Creatinine

Monitoring safety through lab creatinine levels

Time frame: 32 weeks

Albumin

Monitoring safety through lab albumin levels

Time frame: 32 weeks

Hematocrit

Monitoring safety through lab hematocrit levels

Time frame: 32 weeks

Hemoglobin

Monitoring safety through lab hemoglobin levels

Time frame: 32 weeks

Red Blood Cell Count

Monitoring safety through lab red blood cell count levels

Time frame: 32 weeks

White Blood Cell Count

Monitoring safety through lab white blood cell count levels

Time frame: 32 weeks

Platelets

Monitoring safety through lab platelet levels

Time frame: 32 weeks

Serum Haptoglobin

Monitoring safety through lab serum haptoglobin levels

Time frame: 32 weeks

Plasma-Free Hemoglobin

Monitoring safety through lab plasma-free hemoglobin

Time frame: 32 weeks

Direct Coombs' Test

Monitoring safety through Direct Coombs' test

Time frame: 32 weeks

D-dimers

Monitoring safety through D-dimers test

Time frame: 32 weeks

Serum IgG

Monitoring safety through lab IgG levels

Time frame: 32 weeks

Aldolase

Monitoring safety through lab aldolase levels

Time frame: 32 weeks

Creatine Kinase

Monitoring safety through lab creatine kinase levels

Time frame: 32 weeks

Pregnancy Test

Monitoring safety through pregnancy test

Time frame: 32 weeks

Urine Protein

Monitoring safety through lab urine protein levels

Time frame: 32 weeks

Urine Glucose

Monitoring safety through lab urine glucose levels

Time frame: 32 weeks

Urine pH

Monitoring safety through lab urine pH levels

Time frame: 32 weeks

Urine Nitrite

Monitoring safety through lab urine nitrite levels

Time frame: 32 weeks

Urine Ketones

Monitoring safety through lab urine ketone levels

Time frame: 32 weeks

Urine Leukocytes

Monitoring safety through lab urine leukocyte levels

Time frame: 32 weeks

Urine Hemoglobin

Monitoring safety through lab urine hemoglobin levels

Time frame: 32 weeks

Urine Bilirubin

Monitoring safety through lab urine bilirubin levels

Time frame: 32 weeks

Urine Urobilinogen

Monitoring safety through lab urine urobilinogen levels

Time frame: 32 weeks

Urine Hemosiderin

Monitoring safety through lab urine hemosiderin levels

Time frame: 32 weeks

HIV

Monitoring safety through HIV testing

Time frame: 32 weeks

Hepatitis B

Monitoring safety through hepatitis B testing

Time frame: 32 weeks

Hepatitis C

Monitoring safety through hepatitis C testing

Time frame: 32 weeks