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)

Status

Terminated

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03686969

Enrollment

Registered

2018-09-27

Start date

2018-08-02

Completion date

2018-11-29

Last updated

2021-04-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Dermatomyositis

Brief summary

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

Interventions

DRUGOctanorm

Octanorm 0.5g/kg/week

OTHERPlacebo

Placebo

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 80 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
MMT-8	32 weeks	MMT-8; a set of 8 designated muscles tested bilaterally \[potential score 0 - 150\]
CDASI	32 weeks	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.
Physician's Global Disease Activity VAS Worsening	32 weeks	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).

Secondary

Measure	Time frame	Description
D-dimers	32 weeks	Monitoring safety through D-dimers test
Platelets	32 weeks	Monitoring safety through lab platelet levels
Serum Haptoglobin	32 weeks	Monitoring safety through lab serum haptoglobin levels
Extra-Muscular Disease Activity	32 weeks	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).
Muscle Enzymes - Aldolase	32 weeks	Measurement of aldolase in blood
Muscle Enzymes - Creatine Kinase	32 weeks	Measurement of creatine kinase in blood
Muscle Enzymes - Alanine Aminotransferase	32 weeks	Measurement of alanine aminotransferase in blood
Muscle Enzymes - Aspartate Aminotransferase	32 weeks	Measurement of aspartate aminotransferase in blood
Muscle Enzymes - Lactate Dehydrogenase	32 weeks	Measurement of lactate dehydrogenase in blood
Health Assessment Questionnaire	32 weeks	• 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).
SF-36v2 Health Survey	32 weeks	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.
Mean Change in TIS	32 weeks	Total Improvement Score
Time to Clinically Important Deterioration	32 weeks	Time to clinically important deterioration
Adverse Events	32 weeks	Occurrence of all adverse events
TEEs	32 weeks	Monitoring safety with occurrence of all thromboembolic events (TEEs)
Plasma-Free Hemoglobin	32 weeks	Monitoring safety through lab plasma-free hemoglobin
Direct Coombs' Test	32 weeks	Monitoring safety through Direct Coombs' test
HTRs	32 weeks	Monitoring safety with occurrence of all hemolytic transfusion reactions (HTRs)
Injection Site Reactions	32 weeks	Monitoring safety by assessing local injection site reactions
Blood Pressure	32 weeks	Monitoring safety through blood pressure values
Heart Rate	32 weeks	Monitoring safety through heart rate values
Body Temperature	32 weeks	Monitoring safety through body temperature values
Respiratory Rate	32 weeks	Monitoring safety through respiratory rate values
Physical Examination	32 Weeks	The physical examination outcome will be analyzed based on changes from baseline as adverse events.
Sodium	32 weeks	Monitoring safety through lab sodium levels
Potassium	32 weeks	Monitoring safety through lab potassium levels
Glucose	32 weeks	Monitoring safety through lab glucose levels
ALAT	32 weeks	Monitoring safety through lab ALAT levels
ASAT	32 weeks	Monitoring safety through lab ASAT levels
LDH	32 weeks	Monitoring safety through lab LDH levels
Total Bilirubin	32 weeks	Monitoring safety through lab total bilirubin levels
Blood Urea Nitrogen	32 weeks	Monitoring safety through lab blood urea nitrogen levels
Urea	32 weeks	Monitoring safety through lab urea levels
Creatinine	32 weeks	Monitoring safety through lab creatinine levels
Albumin	32 weeks	Monitoring safety through lab albumin levels
Hematocrit	32 weeks	Monitoring safety through lab hematocrit levels
Hemoglobin	32 weeks	Monitoring safety through lab hemoglobin levels
Red Blood Cell Count	32 weeks	Monitoring safety through lab red blood cell count levels
White Blood Cell Count	32 weeks	Monitoring safety through lab white blood cell count levels
Serum IgG	32 weeks	Monitoring safety through lab IgG levels
Aldolase	32 weeks	Monitoring safety through lab aldolase levels
Creatine Kinase	32 weeks	Monitoring safety through lab creatine kinase levels
Pregnancy Test	32 weeks	Monitoring safety through pregnancy test
Urine Protein	32 weeks	Monitoring safety through lab urine protein levels
Urine Glucose	32 weeks	Monitoring safety through lab urine glucose levels
Urine pH	32 weeks	Monitoring safety through lab urine pH levels
Urine Nitrite	32 weeks	Monitoring safety through lab urine nitrite levels
Urine Ketones	32 weeks	Monitoring safety through lab urine ketone levels
Urine Leukocytes	32 weeks	Monitoring safety through lab urine leukocyte levels
Urine Hemoglobin	32 weeks	Monitoring safety through lab urine hemoglobin levels
Urine Bilirubin	32 weeks	Monitoring safety through lab urine bilirubin levels
Urine Urobilinogen	32 weeks	Monitoring safety through lab urine urobilinogen levels
Urine Hemosiderin	32 weeks	Monitoring safety through lab urine hemosiderin levels
HIV	32 weeks	Monitoring safety through HIV testing
Hepatitis B	32 weeks	Monitoring safety through hepatitis B testing
Hepatitis C	32 weeks	Monitoring safety through hepatitis C testing

Countries

Russia

Participant flow

Participants by arm

Arm	Count
Octanorm 0.5g/kg/week octanorm 16.5% Octanorm: Octanorm 0.5g/kg/week	1
Placebo Placebo Placebo: Placebo	0
Total	1

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Study terminated	1	0

Baseline characteristics

Characteristic	Total	Octanorm
Age, Customized Age	52 years	52 years
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants
Race (NIH/OMB) White	1 Participants	1 Participants
Sex: Female, Male Female	1 Participants	1 Participants
Sex: Female, Male Male	0 Participants	0 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 1	0 / 0
other Total, other adverse events	1 / 1	0 / 0
serious Total, serious adverse events	0 / 1	0 / 0

Outcome results

Primary

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