Study Evaluating Efficacy and Safety of Octanorm in Patients With Dermatomyositis

Double-blind, Randomized, Placebo-Controlled Phase III Study Evaluating Efficacy and Safety of Subcutaneous Human Immunoglobulin (Octanorm) in Patients With Dermatomyositis (SCGAM-02)

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

Study Overview

• Status: Terminated
• Conditions: Dermatomyositis
• Intervention / Treatment: Other: Placebo; Drug: Octanorm

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 119992
    • I.M. SECHENOV FIRST MOSCOW STATE MEDICAL UNIVERSITY Rheumatology Department Of, Clinici Of Nephrology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; Placebo
Experimental: Octanorm; 0.5g/kg/week octanorm 16.5%	Drug: Octanorm; Octanorm 0.5g/kg/week

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MMT-8	MMT-8; a set of 8 designated muscles tested bilaterally [potential score 0 - 150]	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.	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).	32 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	32 weeks
Muscle Enzymes - Aldolase	Measurement of aldolase in blood	32 weeks
Muscle Enzymes - Creatine Kinase	Measurement of creatine kinase in blood	32 weeks
Muscle Enzymes - Alanine Aminotransferase	Measurement of alanine aminotransferase in blood	32 weeks
Muscle Enzymes - Aspartate Aminotransferase	Measurement of aspartate aminotransferase in blood	32 weeks
Muscle Enzymes - Lactate Dehydrogenase	Measurement of lactate dehydrogenase in blood	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).	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.	32 weeks
Mean Change in TIS	Total Improvement Score	32 weeks
Time to Clinically Important Deterioration	Time to clinically important deterioration	32 weeks
Adverse Events	Occurrence of all adverse events	32 weeks
TEEs	Monitoring safety with occurrence of all thromboembolic events (TEEs)	32 weeks
HTRs	Monitoring safety with occurrence of all hemolytic transfusion reactions (HTRs)	32 weeks
Injection Site Reactions	Monitoring safety by assessing local injection site reactions	32 weeks
Blood Pressure	Monitoring safety through blood pressure values	32 weeks
Heart Rate	Monitoring safety through heart rate values	32 weeks
Body Temperature	Monitoring safety through body temperature values	32 weeks
Respiratory Rate	Monitoring safety through respiratory rate values	32 weeks
Physical Examination	The physical examination outcome will be analyzed based on changes from baseline as adverse events.	32 Weeks
Sodium	Monitoring safety through lab sodium levels	32 weeks
Potassium	Monitoring safety through lab potassium levels	32 weeks
Glucose	Monitoring safety through lab glucose levels	32 weeks
ALAT	Monitoring safety through lab ALAT levels	32 weeks
ASAT	Monitoring safety through lab ASAT levels	32 weeks
LDH	Monitoring safety through lab LDH levels	32 weeks
Total Bilirubin	Monitoring safety through lab total bilirubin levels	32 weeks
Blood Urea Nitrogen	Monitoring safety through lab blood urea nitrogen levels	32 weeks
Urea	Monitoring safety through lab urea levels	32 weeks
Creatinine	Monitoring safety through lab creatinine levels	32 weeks
Albumin	Monitoring safety through lab albumin levels	32 weeks
Hematocrit	Monitoring safety through lab hematocrit levels	32 weeks
Hemoglobin	Monitoring safety through lab hemoglobin levels	32 weeks
Red Blood Cell Count	Monitoring safety through lab red blood cell count levels	32 weeks
White Blood Cell Count	Monitoring safety through lab white blood cell count levels	32 weeks
Platelets	Monitoring safety through lab platelet levels	32 weeks
Serum Haptoglobin	Monitoring safety through lab serum haptoglobin levels	32 weeks
Plasma-Free Hemoglobin	Monitoring safety through lab plasma-free hemoglobin	32 weeks
Direct Coombs' Test	Monitoring safety through Direct Coombs' test	32 weeks
D-dimers	Monitoring safety through D-dimers test	32 weeks
Serum IgG	Monitoring safety through lab IgG levels	32 weeks
Aldolase	Monitoring safety through lab aldolase levels	32 weeks
Creatine Kinase	Monitoring safety through lab creatine kinase levels	32 weeks
Pregnancy Test	Monitoring safety through pregnancy test	32 weeks
Urine Protein	Monitoring safety through lab urine protein levels	32 weeks
Urine Glucose	Monitoring safety through lab urine glucose levels	32 weeks
Urine pH	Monitoring safety through lab urine pH levels	32 weeks
Urine Nitrite	Monitoring safety through lab urine nitrite levels	32 weeks
Urine Ketones	Monitoring safety through lab urine ketone levels	32 weeks
Urine Leukocytes	Monitoring safety through lab urine leukocyte levels	32 weeks
Urine Hemoglobin	Monitoring safety through lab urine hemoglobin levels	32 weeks
Urine Bilirubin	Monitoring safety through lab urine bilirubin levels	32 weeks
Urine Urobilinogen	Monitoring safety through lab urine urobilinogen levels	32 weeks
Urine Hemosiderin	Monitoring safety through lab urine hemosiderin levels	32 weeks
HIV	Monitoring safety through HIV testing	32 weeks
Hepatitis B	Monitoring safety through hepatitis B testing	32 weeks
Hepatitis C	Monitoring safety through hepatitis C testing	32 weeks

Collaborators and Investigators

• Sponsor: Octapharma

Study record dates

Study Major Dates

• Study Start (Actual): August 2, 2018
• Primary Completion (Actual): November 22, 2018
• Study Completion (Actual): November 29, 2018

Study Registration Dates

• First Submitted: August 31, 2018
• First Submitted That Met QC Criteria: September 25, 2018
• First Posted (Actual): September 27, 2018

Study Record Updates

• Last Update Posted (Actual): April 23, 2021
• Last Update Submitted That Met QC Criteria: April 22, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Skin Diseases; Musculoskeletal Diseases; Connective Tissue Diseases; Muscular Diseases; Neuromuscular Diseases; Polymyositis; Myositis; Dermatomyositis
• Other Study ID Numbers: SCGAM-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No