Study Evaluating Efficacy and Safety of Octanorm in Patients With Dermatomyositis

Dermatomyositis Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03686969
• Other study ID #: SCGAM-02
• Status: Terminated
• Phase: Phase 3
• Start date: August 2, 2018
• Est. completion date: November 29, 2018

Study information

• Verified date: April 2021
• Source: Octapharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: November 29, 2018
• Est. primary completion date: November 22, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Dermatomyositis

Intervention

Drug:
• Octanorm
Octanorm 0.5g/kg/week

Other:
• Placebo
Placebo

Locations

Country	Name	City	State
Russian Federation	I.M. SECHENOV FIRST MOSCOW STATE MEDICAL UNIVERSITY Rheumatology Department Of, Clinici Of Nephrology	Moscow

Sponsors (1)

Lead Sponsor	Collaborator
Octapharma

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MMT-8	MMT-8; a set of 8 designated muscles tested bilaterally [potential score 0 - 150]	32 weeks
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.	32 weeks
Primary	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	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
Secondary	Muscle Enzymes - Aldolase	Measurement of aldolase in blood	32 weeks
Secondary	Muscle Enzymes - Creatine Kinase	Measurement of creatine kinase in blood	32 weeks
Secondary	Muscle Enzymes - Alanine Aminotransferase	Measurement of alanine aminotransferase in blood	32 weeks
Secondary	Muscle Enzymes - Aspartate Aminotransferase	Measurement of aspartate aminotransferase in blood	32 weeks
Secondary	Muscle Enzymes - Lactate Dehydrogenase	Measurement of lactate dehydrogenase in blood	32 weeks
Secondary	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
Secondary	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
Secondary	Mean Change in TIS	Total Improvement Score	32 weeks
Secondary	Time to Clinically Important Deterioration	Time to clinically important deterioration	32 weeks
Secondary	Adverse Events	Occurrence of all adverse events	32 weeks
Secondary	TEEs	Monitoring safety with occurrence of all thromboembolic events (TEEs)	32 weeks
Secondary	HTRs	Monitoring safety with occurrence of all hemolytic transfusion reactions (HTRs)	32 weeks
Secondary	Injection Site Reactions	Monitoring safety by assessing local injection site reactions	32 weeks
Secondary	Blood Pressure	Monitoring safety through blood pressure values	32 weeks
Secondary	Heart Rate	Monitoring safety through heart rate values	32 weeks
Secondary	Body Temperature	Monitoring safety through body temperature values	32 weeks
Secondary	Respiratory Rate	Monitoring safety through respiratory rate values	32 weeks
Secondary	Physical Examination	The physical examination outcome will be analyzed based on changes from baseline as adverse events.	32 Weeks
Secondary	Sodium	Monitoring safety through lab sodium levels	32 weeks
Secondary	Potassium	Monitoring safety through lab potassium levels	32 weeks
Secondary	Glucose	Monitoring safety through lab glucose levels	32 weeks
Secondary	ALAT	Monitoring safety through lab ALAT levels	32 weeks
Secondary	ASAT	Monitoring safety through lab ASAT levels	32 weeks
Secondary	LDH	Monitoring safety through lab LDH levels	32 weeks
Secondary	Total Bilirubin	Monitoring safety through lab total bilirubin levels	32 weeks
Secondary	Blood Urea Nitrogen	Monitoring safety through lab blood urea nitrogen levels	32 weeks
Secondary	Urea	Monitoring safety through lab urea levels	32 weeks
Secondary	Creatinine	Monitoring safety through lab creatinine levels	32 weeks
Secondary	Albumin	Monitoring safety through lab albumin levels	32 weeks
Secondary	Hematocrit	Monitoring safety through lab hematocrit levels	32 weeks
Secondary	Hemoglobin	Monitoring safety through lab hemoglobin levels	32 weeks
Secondary	Red Blood Cell Count	Monitoring safety through lab red blood cell count levels	32 weeks
Secondary	White Blood Cell Count	Monitoring safety through lab white blood cell count levels	32 weeks
Secondary	Platelets	Monitoring safety through lab platelet levels	32 weeks
Secondary	Serum Haptoglobin	Monitoring safety through lab serum haptoglobin levels	32 weeks
Secondary	Plasma-Free Hemoglobin	Monitoring safety through lab plasma-free hemoglobin	32 weeks
Secondary	Direct Coombs' Test	Monitoring safety through Direct Coombs' test	32 weeks
Secondary	D-dimers	Monitoring safety through D-dimers test	32 weeks
Secondary	Serum IgG	Monitoring safety through lab IgG levels	32 weeks
Secondary	Aldolase	Monitoring safety through lab aldolase levels	32 weeks
Secondary	Creatine Kinase	Monitoring safety through lab creatine kinase levels	32 weeks
Secondary	Pregnancy Test	Monitoring safety through pregnancy test	32 weeks
Secondary	Urine Protein	Monitoring safety through lab urine protein levels	32 weeks
Secondary	Urine Glucose	Monitoring safety through lab urine glucose levels	32 weeks
Secondary	Urine pH	Monitoring safety through lab urine pH levels	32 weeks
Secondary	Urine Nitrite	Monitoring safety through lab urine nitrite levels	32 weeks
Secondary	Urine Ketones	Monitoring safety through lab urine ketone levels	32 weeks
Secondary	Urine Leukocytes	Monitoring safety through lab urine leukocyte levels	32 weeks
Secondary	Urine Hemoglobin	Monitoring safety through lab urine hemoglobin levels	32 weeks
Secondary	Urine Bilirubin	Monitoring safety through lab urine bilirubin levels	32 weeks
Secondary	Urine Urobilinogen	Monitoring safety through lab urine urobilinogen levels	32 weeks
Secondary	Urine Hemosiderin	Monitoring safety through lab urine hemosiderin levels	32 weeks
Secondary	HIV	Monitoring safety through HIV testing	32 weeks
Secondary	Hepatitis B	Monitoring safety through hepatitis B testing	32 weeks
Secondary	Hepatitis C	Monitoring safety through hepatitis C testing	32 weeks