Clinical trial NCT03686969: Study Evaluating Efficacy and Safety of Octanorm in Patients With Dermatomyositis
Official title: Double-blind, Randomized, Placebo-Controlled Phase III Study Evaluating Efficacy and Safety of Subcutaneous Human Immunoglobulin (Octanorm) in Patients With Dermatomyositis (SCGAM-02)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Dermatomyositis
Lead sponsor: Octapharma
Sponsor class: INDUSTRY
First posted: 2018-09-27
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: MMT-8
timeFrame: 32 weeks
measure: CDASI
timeFrame: 32 weeks
measure: Physician's Global Disease Activity VAS Worsening
timeFrame: 32 weeks
Secondary outcomes:
measure: Extra-Muscular Disease Activity
timeFrame: 32 weeks
measure: Muscle Enzymes - Aldolase
timeFrame: 32 weeks
measure: Muscle Enzymes - Creatine Kinase
timeFrame: 32 weeks
measure: Muscle Enzymes - Alanine Aminotransferase
timeFrame: 32 weeks
measure: Muscle Enzymes - Aspartate Aminotransferase
timeFrame: 32 weeks
measure: Muscle Enzymes - Lactate Dehydrogenase
timeFrame: 32 weeks
measure: Health Assessment Questionnaire
timeFrame: 32 weeks
measure: SF-36v2 Health Survey
timeFrame: 32 weeks
measure: Mean Change in TIS
timeFrame: 32 weeks
measure: Time to Clinically Important Deterioration
timeFrame: 32 weeks
measure: Adverse Events
timeFrame: 32 weeks
measure: TEEs
timeFrame: 32 weeks
measure: HTRs
timeFrame: 32 weeks
measure: Injection Site Reactions
timeFrame: 32 weeks
measure: Blood Pressure
timeFrame: 32 weeks
measure: Heart Rate
timeFrame: 32 weeks
measure: Body Temperature
timeFrame: 32 weeks
measure: Respiratory Rate
timeFrame: 32 weeks
measure: Physical Examination
timeFrame: 32 Weeks
measure: Sodium
timeFrame: 32 weeks
measure: Potassium
timeFrame: 32 weeks
measure: Glucose
timeFrame: 32 weeks
measure: ALAT
timeFrame: 32 weeks
measure: ASAT
timeFrame: 32 weeks
measure: LDH
timeFrame: 32 weeks
measure: Total Bilirubin
timeFrame: 32 weeks
measure: Blood Urea Nitrogen
timeFrame: 32 weeks
measure: Urea
timeFrame: 32 weeks
measure: Creatinine
timeFrame: 32 weeks
measure: Albumin
timeFrame: 32 weeks
measure: Hematocrit
timeFrame: 32 weeks
measure: Hemoglobin
timeFrame: 32 weeks
measure: Red Blood Cell Count
timeFrame: 32 weeks
measure: White Blood Cell Count
timeFrame: 32 weeks
measure: Platelets
timeFrame: 32 weeks
measure: Serum Haptoglobin
timeFrame: 32 weeks
measure: Plasma-Free Hemoglobin
timeFrame: 32 weeks
measure: Direct Coombs' Test
timeFrame: 32 weeks
measure: D-dimers
timeFrame: 32 weeks
measure: Serum IgG
timeFrame: 32 weeks
measure: Aldolase
timeFrame: 32 weeks
measure: Creatine Kinase
timeFrame: 32 weeks
measure: Pregnancy Test
timeFrame: 32 weeks
measure: Urine Protein
timeFrame: 32 weeks
measure: Urine Glucose
timeFrame: 32 weeks
measure: Urine pH
timeFrame: 32 weeks
measure: Urine Nitrite
timeFrame: 32 weeks
measure: Urine Ketones
timeFrame: 32 weeks
measure: Urine Leukocytes
timeFrame: 32 weeks
measure: Urine Hemoglobin
timeFrame: 32 weeks
measure: Urine Bilirubin
timeFrame: 32 weeks
measure: Urine Urobilinogen
timeFrame: 32 weeks
measure: Urine Hemosiderin
timeFrame: 32 weeks
measure: HIV
timeFrame: 32 weeks
measure: Hepatitis B
timeFrame: 32 weeks
measure: Hepatitis C
timeFrame: 32 weeks
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: I.M. SECHENOV FIRST MOSCOW STATE MEDICAL UNIVERSITY Rheumatology Department Of, Clinici Of Nephrology
Study officials:
References: