Clinical trial NCT02728752: Study Evaluating Efficacy and Safety of Octagam 10% in Patients With Dermatomyositis (Idiopathic Inflammatory Myopathy)
Official title: Prospective, Double-blind, Randomized, Placebo-Controlled Phase III Study Evaluating Efficacy and Safety of Octagam 10% in Patients With Dermatomyositis ("ProDERM Study")
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Dermatomyositis
Keywords: DM
Lead sponsor: Octapharma
Sponsor class: INDUSTRY
First posted: 2016-04-05
Enrollment: 95
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Prospective, Double-blind, Randomized, Placebo-Controlled Phase III Study Evaluating Efficacy and Safety of Octagam 10% in Patients With Dermatomyositis ("ProDERM study")


Eligibility criteria: Inclusion Criteria:

1. Subjects with diagnosis of definite or probable DM according to the Bohan and Peter criteria.
2. Subjects under treatment with corticosteroids and/or maximally 2 immune-suppressants and being on stable therapy for at least 4 weeks (see Section 4.2.1) OR Subjects with previous failure of response or previous intolerance to corticosteroid and at least 1 additional immunosuppressive drug, and with steroid/immunosuppressive drugs washed out as per Section 4.2.1 (Table 2).
3. Subjects with active disease, assessed and agreed upon by an independent adjudication committee.
4. Manual Muscle Testing-8 (MMT-8) score \<142, with at least 2 other abnormal Core Set Measures (CSM) (Visual Analogue Scale \[VAS\] of patient global activity ≥2 cm, physician's global disease activity ≥2 cm, extra-muscular activity ≥2 cm; at least one muscle enzyme \>1.5 times upper limit of normal, Health Assessment Questionnaire ≥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 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.
3. Subjects with overlap myositis (except for overlap with Sjögren's syndrome), connective tissue disease associated DM, inclusion body myositis, polymyositis, juvenile dermatomyositis 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 have received IgG treatment within the last 6 months before enrolment.
7. Subjects who received blood or plasma-derived products (other than IgG) or plasma exchange within the last 3 months before enrolment.
8. Subjects starting or planning to start a physical therapy-directed exercise regimen during the trial.
9. Cardiac insufficiency (New York Heart Association III/IV), cardiomyopathy, significant cardiac dysrhythmia requiring treatment, unstable or advanced ischemic heart disease.
10. Severe liver disease, with signs of ascites and hepatic encephalopathy.
11. Severe kidney disease (as defined by estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73 m2).
12. Known hepatitis B, hepatitis C or HIV infection.
13. Subjects with a history of TEE such as deep vein thrombosis, pulmonary embolism, myocardial infarction, ischemic stroke, transient ischemic attack, peripheral artery disease (Fontaine IV) ever.
14. Body mass index ≥40 kg/m2.
15. Medical conditions whose symptoms and effects could alter protein catabolism and/or IgG utilization (e.g. protein-losing enteropathies, nephrotic syndrome).
16. Known IgA deficiency with antibodies to IgA.
17. History of hypersensitivity, anaphylaxis or severe systemic response to immuno-globulin, blood or plasma derived products or any component of Octagam 10%.
18. Known blood hyperviscosity, or other hypercoagulable states.
19. Subjects with a history of drug abuse within the past 5 years prior to study enrollment.
20. Subjects unable or unwilling to understand or comply with the study protocol.
21. Participating in another interventional clinical study with investigational treatment within 3 months prior to study enrollment.
22. Women who are breast feeding, pregnant, or planning to become pregnant, or are unwilling to apply an effective birth control method (such as implants, injectables, combined oral contraceptives, some intrauterine devices \[IUDs\], sexual abstinence or vasectomized partner) up to four weeks after the last IMP infusion.
23. Subjects who are accommodated in an institution or care facility based on an official directive or court order.
24. Subjects who are in any way dependent on the Sponsor, Investigator or Study Site.
25. Subjects who received forbidden medication within the washout period as defined in Section 4.2.2 (Table 3).

Primary outcomes:
measure: Measure the Number of Patients Who Had an Increase of ≥20 Points on the Total Improvement Score (TIS)
timeFrame: At week 16
Secondary outcomes:
measure: Proportion of TIS Responders by Improvement Category at Week 16
timeFrame: 16 weeks
measure: Proportion of TIS Responders by Improvement Category at Week 40
timeFrame: 40 weeks
measure: Mean Change From Baseline (Week 0) to End of First Period (Week 16) in the Modified Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI)
timeFrame: First 16 weeks
measure: Mean Change From End of First Period (Week 16) to End of Extension Period (Week 40) in the Modified Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI)
timeFrame: From week 16 to Week 40
measure: Mean Change From Baseline (Week 0) to End of Extension Period (Week 40) in the Modified Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI)
timeFrame: 40 weeks
measure: Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in: SF-36v2 Health Survey
timeFrame: From start of the trial till Week 40
measure: Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in Physician's Global Disease Activity
timeFrame: From start of the trial till Week 40
measure: Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in: Patient Global Disease Activity
timeFrame: From start of the trial till Week 40
measure: Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in: MMT-8
timeFrame: From start of the trial till Week 40
measure: Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in: Health Assessment Questionnaire
timeFrame: From start of the trial till Week 40
measure: Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in Enzymes (Alanine Aminotransferase)
timeFrame: From start of the trial till Week 40
measure: Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in Enzymes (Aspartate Aminotransferase)
timeFrame: From start of the trial till Week 40
measure: Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in Enzymes (Lactate Dehydrogenase)
timeFrame: From start of the trial till Week 40
measure: Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in Enzymes (Aldolase)
timeFrame: From start of the trial till Week 40
measure: Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in Enzymes (Creatine Kinase)
timeFrame: From start of the trial till Week 40
measure: Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in: Extra-muscular Activity
timeFrame: From start of the trial until Week 40
measure: Mean TIS From Baseline (Week 0) to End of First Period (Week 16) and From Baseline (Week 0) to End of Extension Period (Week 40)
timeFrame: Up to 40 weeks
measure: Time to Minimal, Moderate and Major Improvement in TIS
timeFrame: Up to 40 weeks
measure: Time to Confirmed Deterioration in the First Period and Overall
timeFrame: Up to 40 weeks
Other outcomes:
Locations:
city: Huntington Beach
country: United States
facility: Octapharma Research Site
state: California
city: Los Angeles
country: United States
facility: Octapharma Research Site
state: California
city: Orange
country: United States
facility: University of California -Irvine
state: California
city: Orlando
country: United States
facility: Octapharma Research Site
state: Florida
city: Panama City
country: United States
facility: NeuroMedical Research Center
state: Florida
city: Plantation
country: United States
facility: Octapharma Research Site
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Kansas City
country: United States
facility: Octapharma Research Site
state: Kansas
city: Ann Arbor
country: United States
facility: Octapharma Research Site
state: Michigan
city: Rochester
country: United States
facility: Octapharma Research Site
state: Minnesota
city: Great Neck
country: United States
facility: Octapharma Research Site
state: New York
city: Portland
country: United States
facility: Octapharma Research Site
state: Oregon
city: Pittsburgh
country: United States
facility: Octapharma Research Site
state: Pennsylvania
city: Murfreesboro
country: United States
facility: Stones River Dermatology
state: Tennessee
city: Austin
country: United States
facility: Austin Neuromuscular Center
state: Texas
city: Houston
country: United States
facility: Octapharma Research Site
state: Texas
city: Waco
country: United States
facility: Arthritis & Osteoporosis Clinic
state: Texas
city: Montréal
country: Canada
facility: Octapharma Research Site
state: Quebec
city: Praha
country: Czechia
facility: Revmatologický ústav
city: Berlin
country: Germany
facility: Charité-Universitätsmedizin Berlin, Klinik für Dermatologie, Venerologie und Allergologie
city: Münster
country: Germany
facility: Uniklinikum Münster, Klinik für Hautkrankheiten
city: Budapest
country: Hungary
facility: Semmelweis University Dermatology Clinic
city: Debrecen
country: Hungary
facility: University of Debrecen Dept of Internal Medicine
city: Szeged
country: Hungary
facility: University of Szeged Dermatology Clinic
city: Amsterdam
country: Netherlands
facility: Academic Medical Centre University of Amsterdam
city: Kraków
country: Poland
facility: Centrum Medyczne Plejady
city: Warsaw
country: Poland
facility: Narodowy Instytut Geriatrii, Reumatologii I Rehabilitacji - Warsaw
city: Cluj-Napoca
country: Romania
facility: Octapharma Research Site
city: Moscow
country: Russian Federation
facility: Scientific Research Institute for Rheumatology (Moscow)
city: Moscow
country: Russian Federation
facility: I.M. Sechenov First Moscow State Medical University
city: Orenburg
country: Russian Federation
facility: Orenburg State Medical University Based On Regional Clinical Hospital
city: Saint Petersburg
country: Russian Federation
facility: 3rd Rheumatology Department Of Clinical Rheumatology Hospital No. 25
city: Saint Petersburg
country: Russian Federation
facility: AVA-Peter clinic (Saint-Petersburg)
city: Ivano-Frankivs'k
country: Ukraine
facility: Octapharma Research Site
city: Lviv
country: Ukraine
facility: Octapharma Research Site
city: Sumy
country: Ukraine
facility: Octapharma Research Site
city: Ternopil'
country: Ukraine
facility: Octapharma Research Site
Study officials:
affiliation: International Medical Director
name: Wolfgang Frenzel
role: STUDY_DIRECTOR
References:
citation: Aggarwal R, Charles-Schoeman C, Schessl J, Bata-Csorgo Z, Dimachkie MM, Griger Z, Moiseev S, Oddis C, Schiopu E, Vencovsky J, Beckmann I, Clodi E, Bugrova O, Danko K, Ernste F, Goyal NA, Heuer M, Hudson M, Hussain YM, Karam C, Magnolo N, Nelson R, Pozur N, Prystupa L, Sardy M, Valenzuela G, van der Kooi AJ, Vu T, Worm M, Levine T; ProDERM Trial Group. Trial of Intravenous Immune Globulin in Dermatomyositis. N Engl J Med. 2022 Oct 6;387(14):1264-1278. doi: 10.1056/NEJMoa2117912.
citation: Aggarwal R, Charles-Schoeman C, Schessl J, Dimachkie MM, Beckmann I, Levine T. Prospective, double-blind, randomized, placebo-controlled phase III study evaluating efficacy and safety of octagam 10% in patients with dermatomyositis ("ProDERM Study"). Medicine (Baltimore). 2021 Jan 8;100(1):e23677. doi: 10.1097/MD.0000000000023677.