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

• Register: EUCTR
• Last refreshed on: 26 November 2018
• Main ID: EUCTR2017-002710-31-DE
• Date of registration: 24/05/2018
• Prospective Registration: Yes
• Primary sponsor: Octapharma Pharmazeutika Produktionsges.m.b.H
• Public title: DOUBLE-BLIND, RANDOMIZED, PLACEBO- CONTROLLED PHASE III STUDY EVALUATING EFFICACY AND SAFETY OF SUBCUTANEOUS HUMAN IMMUNOGLOBULIN (OCTANORM) IN PATIENTS WITH DERMATOMYOSITIS.
• Scientific title: DOUBLE-BLIND, RANDOMIZED, PLACEBO- CONTROLLED PHASE III STUDY EVALUATING EFFICACY AND SAFETY OF SUBCUTANEOUS HUMAN IMMUNOGLOBULIN (OCTANORM) IN PATIENTS WITH DERMATOMYOSITIS.
• Date of first enrolment: 20/08/2018
• Target sample size: 78
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-002710-31
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Canada, Czech Republic, Germany, Hungary, Netherlands, Poland, Romania, Russian Federation, United States

Contacts

• Name: Global Clinical Project Manager
• Affiliation: Octapharma Pharmazeutika Produktionsges.m.b.H.

• Name: Global Clinical Project Manager
• Affiliation: Octapharma Pharmazeutika Produktionsges.m.b.H.

Key inclusion & exclusion 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%) prior to study enrolment.
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

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 70
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 8

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 at least 1 year for basal or squamous cell skin cancer and 5 years for carcinoma in situ of the cervix must have passed since excision).
2-Evidence of active malignant disease or malignancies diagnosed within the previous 5 years (including hematological malignancies and solid tumors).
3-Subjects with overlap myositis 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 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
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).
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 active or chronic hepatitis B, hepatitis C or HIV infection. Past hepatitis B or C infection that has been cured is allowed.
14-Subjects with a history of deep vein thrombosis within the last year prior to study enrolment or pulmonary embolism.
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.
17-Known IgA deficiency with antibodies to IgA.
18-History of hypersensitivity, anaphylaxis or severe systemic response to immuno- globulin, 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 except study GAM10-08.
22-Women who are breast feeding, pregnant, or planning to become pregnant during study.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Dermatomyositis
MedDRA version: 20.0 Level: PT Classification code 10012503 Term: Dermatomyositis System Organ Class: 10040785 - Skin and subcutaneous tissue disorders

Intervention(s)

Product Name: Octanorm 16.5%
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Human Normal Immunoglobulin
CAS Number: 308067-58-5
Current Sponsor code: Octanorm 16.5%
Other descriptive name: HUMAN NORMAL IMMUNOGLOBULIN
Concentration unit: % percent
Concentration type: equal
Concentration number: 16.5-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Main Objective: The primary objective of this study is to determine the efficacy of subcutaneous immunoglobulin octanorm in the maintenance treatment of DM patients who have previously responded to IGIV therapy.

Timepoint(s) of evaluation of this end point: End of the study

Primary end point(s): Proportion of patients with clinically important deterioration during the treatment period up to Week 32. A patient with clinically important deterioration is defined as a patient with 1) MMT-8 worsening = 6 points (scale of 150) OR CDASI (Total Activity Score)worsening = 5 points, AND 2) a Physician’s Global Disease Activity VAS worsening 2 cm.

Secondary Objective: The secondary objectives of this study are:
•to assess other efficacy outcomes at the end of study (Week 32 or Drop-out Visit);
•to assess the effect of octanorm on Quality of Life measures;
•to assess the treatment compliance of home treatment with octanorm;
to evaluate the safety and tolerability of octanorm in subjects with Dermatomyositis

Secondary Outcome(s)

Secondary end point(s): •Mean change from baseline (Week 0-defined as end of IGIV therapy) to end of the treatment period (Week 32 or Drop-out Visit) in:
oModified Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI);
oSix Myositis CSM: MMT-8, Physician’s Global Disease Activity, Patient’s Global Disease Activity, Extra-Muscular Disease Activity, Muscle enzymes, Health Assessment Questionnaire (HAQ);
oSF-36v2 Health Survey.
•Mean change in TIS from Baseline (Week 0) to end of treatment period (Week 32 or Drop-out Visit).
•Time to clinically important deterioration during the treatment period.
•Number and type of deviations from protocol requirements relating to home treatment (dosing, timing).

Timepoint(s) of evaluation of this end point: End of the study

Secondary ID(s)

SCGAM-02

17515

Source(s) of Monetary Support

Octapharma Pharmazeutika Produktionsges.m.b.H.