A study investigating Immune Globulin (Human), 10% Caprylate/Chromatography Purified (IGIV-C) for the treatment of patients with Myasthenia Gravis. The patients will receive 2g/kg of IP as a loading dose. The loading dosage is followed by maintenance doses of 1 g/kg administered every third week until Visit 8 (Week 21).

• Register: EUCTR
• Last refreshed on: 30 April 2018
• Main ID: EUCTR2014-003997-18-LT
• Date of registration: 25/05/2015
• Prospective Registration: Yes
• Primary sponsor: Grifols Therapeutics Inc.
• Public title: A study investigating Immune Globulin (Human), 10% Caprylate/Chromatography Purified (IGIV-C) for the treatment of patients with Myasthenia Gravis. The patients will receive 2g/kg of IP as a loading dose. The loading dosage is followed by maintenance doses of 1 g/kg administered every third week until Visit 8 (Week 21).
• Scientific title: A Multi-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Immune Globulin (Human), 10% Caprylate/ Chromatography Purified (IGIV -C) in Symptomatic Subjects with Generalized Myasthenia Gravis
• Date of first enrolment: 07/07/2015
• Target sample size: 62
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-003997-18
• 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): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Canada, Czech Republic, Estonia, France, Germany, Hungary, Lithuania, Poland, United States

Contacts

• Name: Rhonda Griffin-Director,ClinDev
• Affiliation: Grifols Therapeutics Inc.

• Name: Rhonda Griffin-Director,ClinDev
• Affiliation: Grifols Therapeutics Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female, ages 18 to 85 years
2. Anti-AChR antibody positive
3. Confirmed diagnosis of generalized MG. Historically, subjects may have previously had the Myasthenia Gravis Foundation of America (MGFA) Class II, III, IV, or V.
4. MGFA classification of Class II, III, or IVa inclusive at Screening.
5. QMG score =10 at Screening. Note: Subjects who only have a history of ocular MG may not enroll.
6. Receiving standard of care MG treatment at a stable dose consisting of any one of the following for the time intervals delineated below (time intervals apply to medications and maintenance of stable dose level):
-Cholinesterase inhibitor (pyridostigmine or equivalent) for at least 2 weeks prior to Screening and no immunosuppressants
- Cholinesterase inhibitor (pyridostigmine or equivalent) for at least 2 weeks priorto Screening and/or only one of the following:
* Prednisone (up to 60 mg/day or equivalent) for at least two months prior to Screening, or
* Azathioprine for at least 6 months prior to Screening, or
* Mycophenolate mofetil for at least 6 months prior to Screening, or
*Methotrexate for at least 6 months prior to Screening, or
* Cyclosporine or tacrolimus for at least 3 months prior to Screening
- Cholinesterase inhibitor (pyridostigmine or equivalent) for at least 2 weeks prior to Screening and/or prednisone (up to 60 mg/day or equivalent) for at least one month prior to Screening and only one of the following:
* Azathioprine for at least 6 months prior to Screening, or
* Mycophenolate mofetil for at least 6 months prior to Screening, or
*Methotrexate for at least 6 months prior to Screening, or
* Cyclosporine or tacrolimus for at least 3 months prior to Screening
7. Subjects must be willing and able to provide written informed consent
8. Subjects must be willing to comply with all aspects of the clinical trial 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 56
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 6

Exclusion criteria:
1. Have received cyclophosphamide or any other immunosuppressive agent apart from the ones allowed per inclusion criteria within the past 6 months
2. Any change in MG treatment regimen between Screening (Week -3, Visit 0) and Baseline (Week 0, Visit 1)
3. Greater than two (>2) point change in QMG score, increased or decreased, between Screening (Week -3, Visit 0) and Baseline (Week 0, Visit 1)
4. Any episode of myasthenic crisis in the one month prior to Screening
5. Evidence of malignancy within the past 5 years (nonmelanoma skin cancer, carcinoma in situ of cervix is allowed) or thymoma potentially requiring surgical intervention during the course of the trial (intent to perform thymectomy)
6. Thymectomy within the preceding six months
7. Rituximab, belimumab, eculizumab or any monoclonal antibody used for immunomodulation within the past 12 months
8. Have received immune globulin (Ig) treatment given by IV, subcutaneous, or intramuscular route within the last 3 months
9. Current known hyperviscosity or hypercoagulable state
10. Currently receiving anti-coagulation therapy (vitamin K antagonists, nonvitamin K antagonist oral anticoagulants [e.g., dabigatran etexilate, rivaroxaban, edoxaban, and apixaban], parenteral anticoagulants [e.g., fondaparinux]). Note that oral anti-platelet agents are allowed (e.g., aspirin, clopidogrel, ticlodipine)
11. Plasma exchange (PLEX) performed within the last 3 months
12. History of non-response to IVIg when used in maintenance therapy of the subject’s MG, as judged by the Investigator
13. Any comorbid condition that in the opinion of the Investigator would put the subject at undue safety risk or compromise the ability of the subject to participate in the trial or the scientific integrity of the study
14. Inadequate venous access to support repeated intravenous infusions
15. History of anaphylactic reactions or severe reactions to any blood-derived product
16. History of intolerance to any component of the IP
17. Documented diagnosis of thrombotic complications to polyclonal IVIg therapy in the past
18. History of recent (within the last year) myocardial infarction or stroke
19. Uncontrolled congestive heart failure; embolism; or historically documented (within the last year) electrocardiogram (ECG) changes indicative of myocardial ischemia or atrial fibrillation
20. History of chronic alcoholism or illicit drug abuse (addiction) in the 12 months preceding the Screening/Week -3 (Visit 0)
21. Active psychiatric illness that interferes with compliance or communication with health care personnel
22. Females of child-bearing potential who are pregnant or have a positive serum pregnancy test (beta-human chorionic gonadotropin [ß-HCG]-based assay)
23. Females who are breastfeeding
24. Females of child-bearing potential who are unwilling to practice a highly effective method of contraception (oral, injectable or implanted hormonal methods of contraception, placement of an intrauterine device or intrauterine system, condom or occlusive cap with spermicidal foam/gel/film/cream/suppository, male sterilization, or true abstinence*) throughout the study.
* True abstinence: When this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods], declaration of abstinence for the duration of a trial, and withdrawal are not acceptable methods of contraception.)
25. Currently receiving, or having re

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

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Myasthenia Gravis
MedDRA version: 20.0 Level: PT Classification code 10028417 Term: Myasthenia gravis System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Trade Name: GAMUNEX 10%
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Immune Globulin (Human), 10% Caprylate/Chromatography Purified (IGIV-C)
Other descriptive name: HUMAN NORMAL IMMUNOGLOBULIN (IV)
Concentration unit: g/ml gram(s)/millilitre
Concentration type: equal
Concentration number: 0.10-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Throuhout the study from Baseline (Week 0) to Week 24.

Main Objective: The primary objective is to evaluate the efficacy of IGIV-C in subjects with generalized myasthenia gravis (MG) on standard of care treatment at study entry in terms of improvement in MG symptoms as measured by the mean change in Quantitative Myasthenia Gravis (QMG) score from Baseline (Week 0) to Week 24 as compared to placebo.

Primary end point(s): The primary endpoint is improvement in MG symptoms as measured by the mean change in QMG score from Baseline (Week 0) to Week 24 as compared to placebo.

Secondary Objective: 1) Percentage of subjects who experience a clinical improvement assessed by QMG score from Baseline (Week 0) to Week 24 where clinical improvement is defined as at least a 3-point decrease in QMG score
2) Percentage of subjects who experience a clinical improvement assessed by the MG Composite from Baseline (Week 0) to Week 24 where clinical improvement is defined as at least a 3-point decrease in the MG Composite
3) Percentage of subjects who experience a clinical improvement assessed by MG –Activities of Daily Living (MG-ADL) from Baseline (Week 0) to Week 24 where clinical improvement is defined as at least a 2-point decrease in MG-ADL

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1) Throughout the study, from Baseline (Week 0) to Week 24
2) Throughout the study, from Baseline (Week 0) to Week 24
3) Throughout the study, from Baseline (Week 0) to Week 24

Secondary end point(s): 1) Percentage of subjects who experience a clinical improvement assessed by QMG score from Baseline (Week 0) to Week 24 where clinical improvement is defined as at least a 3-point decrease in QMG score
2) Percentage of subjects who experience a clinical improvement assessed by the MG Composite from Baseline (Week 0) to Week 24 where clinical improvement is defined as at least a 3-point decrease in the MG Composite
3) Percentage of subjects who experience a clinical improvement assessed by MG-ADL from Baseline (Week 0) to Week 24 where clinical improvement is defined as at least a 2-point decrease in MG-ADL

Secondary ID(s)

GTI1408

Source(s) of Monetary Support

Grifols Therapeutics Inc.