Protocol summary

Study aim
Evaluation of efficacy and safety of Zytux™ (Rituximab) in refractory myasthenia gravis patients
Design
This phase 4 prospective, single-arm, open-label, pre-post clinical trial study will be conducted in 30 patients with refractory myasthenia gravis.
Settings and conduct
This multi-center study will be conducted in patients with refractory myasthenia gravis in six different cities of Iran with a follow-up duration of 48 weeks. Zytux™ (Rituximab) will be administered to the eligible patients 2 times at day 0 and 15, followed by one single injection 6 months later. The outcomes will be assessed and recorded by a physician through 48 weeks of monitoring of the patients.
Participants/Inclusion and exclusion criteria
Inclusion criteria: Generalized Non-Thymothamous myasthenia gravis patients, Not having previous treatment with rituximab, Refractory to standard treatment or contraindicated including corticosteroid or Azathioprine, Age between 18 and 80 years Exclusion criteria: Pregnancy, Planning for pregnancy in the following year, Lactation, Active infection, HBsAg+ OR HBV DNA Positive, Prior malignancy, Hypersensitivity reactions or anaphylactic shock to rituximab, Major renal disease, Major Hepatic disease, Cardiac Arrhythmia history, Occular myasthenia gravis, Thymomathous myasthenia gravis, Major Psychiatric disease, Doing Thymectomy
Intervention groups
The therapeutic schema is rituximab 1000 mg, 2 times at day 0 and 15, followed by one single injection (1000 mg) 6 months later. However, rituximab infusion will be administered sooner if myasthenic symptoms reappear and interfere with daily life activities of patient (the interval between Rituximab infusions should be at least three months).
Main outcome variables
Changes in the mean dose of corticosteroid used by patients

General information

Reason for update
Acronym
IRCT registration information
IRCT registration number: IRCT20150303021315N18
Registration date: 2020-05-23, 1399/03/03
Registration timing: registered_while_recruiting

Last update: 2020-05-23, 1399/03/03
Update count: 0
Registration date
2020-05-23, 1399/03/03
Registrant information
Name
Nassim Anjidani
Name of organization / entity
Orchid Pharmed
Country
Iran (Islamic Republic of)
Phone
+98 21 4347 3000
Email address
amini@orchidpharmed.com
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2020-02-11, 1398/11/22
Expected recruitment end date
2021-02-10, 1399/11/22
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Evaluation of efficacy and safety of Zytux™ (Rituximab) in refractory myasthenia gravis patients
Public title
Evaluation of efficacy and safety of Zytux™ (Rituximab) in refractory myasthenia gravis patients
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Generalized Non-Thymothamous patients with myasthenia gravis patients including MuSK Antibody positive, AChR Antibody positive, and Seronegative myasthenia gravis patients. Not having previous treatment with rituximab. Refractory to standard treatment or contraindicated including Corticosteroid dependency (taking at least 2 months of 1mg/kg corticosteroid medications and has not responded properly, or being stable with steroid therapy, but during tapering down the medication up to 30 mg alternative or 15 mg daily, has experienced a relapse of the disease); Having contraindication of corticosteroid therapy; Not responder to Azathioprine (2-3 mg/kg) therapy for at least 9 months of taking the medication or because of occurrence of adverse effects of Azathioprine the medication has been stopped. Aged greater or equal to 18, and lesser or equal to 80.
Exclusion criteria:
Pregnancy Planning for pregnancy in the following year Lactation Active infection HBsAg+ OR HBV DNA Positive Prior malignancy Hypersensitivity reactions or anaphylactic shock to rituximab Major renal disease Major Hepatic disease Cardiac Arrhythmia history Occular myasthenia gravis Thymomathous myasthenia gravis Major Psychiatric disease Doing Thymectomy
Age
From 18 years old to 80 years old
Gender
Both
Phase
4
Groups that have been masked
No information
Sample size
Target sample size: 30
Randomization (investigator's opinion)
N/A
Randomization description
Blinding (investigator's opinion)
Not blinded
Blinding description
Placebo
Not used
Assignment
Single
Other design features

Secondary Ids

empty

Ethics committees

1

Ethics committee
Name of ethics committee
Ethics Committee of Tehran University of Medical Sciences
Street address
No. 23, 16th Azar Ave., Keshavarz Blvd.
City
Tehran
Province
Tehran
Postal code
1417863181
Approval date
2020-02-11, 1398/11/22
Ethics committee reference number
IR.TUMS.MEDICINE.REC.1398.879

Health conditions studied

1

Description of health condition studied
Myasthenia gravis
ICD-10 code
G70
ICD-10 code description
Myasthenia gravis and other myoneural disorders

Primary outcomes

1

Description
Changes in the mean dose of corticosteroid used by patients
Timepoint
day 0, day 15, week 12, week 24, week 36, week 48
Method of measurement
Patient’s concomitant medication

Secondary outcomes

1

Description
Safety of Zytux™ (Rituximab) in refractory myasthenia gravis patients
Timepoint
day 0, day 15, week 12, week 24, week 36, week 48
Method of measurement
Physical Examination

2

Description
Time to relapse from the onset of treatment
Timepoint
day 0, day 15, week 12, week 24, week 36, week 48
Method of measurement
Physical Examination

3

Description
Changes in AChR and MuSK antibody levels
Timepoint
day 0 and week 48
Method of measurement
The Serum titer of AChR and MuSK antibodies

4

Description
Changes in the mean dose of pyridostigmine used by patients
Timepoint
day 0, day 15, week 12, week 24, week 36, week 48
Method of measurement
Patient’s concomitant drugs during treatment

5

Description
Changes in CD19 and CD20 levels
Timepoint
week 7, week 24
Method of measurement
Flow Cytometry

Intervention groups

1

Description
The therapeutic process consists of two cycles. In cycle 1, Zytux™ 1000 mg (Aryogen-Pharmed Rituximab concentrated solution of 10mg/ml made for infusion) will be administered 2 times at day 0 and 15 and one single infusion (1000 mg) 6 months later in cycle 2. However, Zytux™ will be administered sooner if myasthenic symptoms reappear and interfere with the daily life activities of the patient (the interval between Zytux™ infusions should be at least three months).
Category
Treatment - Drugs

Recruitment centers

1

Recruitment center
Name of recruitment center
Shariati hospital
Full name of responsible person
Dr Farzad Fatehi
Street address
Jalal Al Ahmad Highway, North Karegar Ave.
City
Tehran
Province
Tehran
Postal code
1411713135
Phone
+98 21 8490 1000
Email
fatehifa@gmail.com

2

Recruitment center
Name of recruitment center
Bahman hospital
Full name of responsible person
Dr Nima Mohsen zadeh Kermani
Street address
North Iranzamin Ave., Shahrak Gharb
City
Tehran
Province
Tehran
Postal code
1465795481
Phone
+98 21 8857 5901
Email
nimamk@yahoo.com

3

Recruitment center
Name of recruitment center
Imam Khomeini hospital
Full name of responsible person
Dr Payam Sarraf
Street address
Keshavarz Blvd.
City
Tehran
Province
Tehran
Postal code
14197333141
Phone
+98 21 6694 8899
Email
sarrafp@gmail.com

4

Recruitment center
Name of recruitment center
Sina hospital
Full name of responsible person
Dr Aliasghar Okhovat
Street address
Imam Khomeini Ave.
City
Tehran
Province
Tehran
Postal code
1136746911
Phone
+98 21 6634 8500
Email
aliokhi20@gmail.com

5

Recruitment center
Name of recruitment center
Imam Hossein hospital
Full name of responsible person
Dr Nahid Beladi Moqadam
Street address
Shahid Madani St.
City
Tehran
Province
Tehran
Postal code
1617763141
Phone
+98 21 7343 3000
Email
nbeladi@yahoo.com

6

Recruitment center
Name of recruitment center
Firoozgar hospital
Full name of responsible person
Bahram Haghi-Ashtiani
Street address
Valiasr Sq.
City
Tehran
Province
Tehran
Postal code
1593747811
Phone
+98 21 8214 1000
Email
bhaghi2000@yahoo.com

7

Recruitment center
Name of recruitment center
Alzahra hospital
Full name of responsible person
Dr Kayvan Basiri
Street address
Soffeh Blvd.
City
Esfahan
Province
Isfehan
Postal code
8174675731
Phone
+98 31 3620 1818
Email
basirik@med.mui.ac.ir

8

Recruitment center
Name of recruitment center
Ayatollah Kashani hospital
Full name of responsible person
Dr Majid Ghasemi
Street address
Ayatollah Kashani Blvd.
City
Esfahan
Province
Isfehan
Postal code
8183983434
Phone
+98 31 3233 0091
Email
ghasemi@med.mui.ac.ir

9

Recruitment center
Name of recruitment center
Shafa hospital
Full name of responsible person
Dr Behnaz Sedighi
Street address
Kosar Blvd.
City
Kerman
Province
Kerman
Postal code
7618751151
Phone
+98 34 3211 5780
Email
behnaz.sedighi@gmail.com

10

Recruitment center
Name of recruitment center
Ghaem hospital
Full name of responsible person
Dr. Reza Bostani
Street address
Ghaem Hospital, Dr. Shariati St., Ahmad Abad, St., Ghaem Hospital
City
Mashhad
Province
Razavi Khorasan
Postal code
9176699199
Phone
+98 51 3840 0001
Email
rezabostani@yahoo.com

11

Recruitment center
Name of recruitment center
Namazi hospital
Full name of responsible person
Dr Abbas Rahimi Jaberi
Street address
Zand Street, Namaz Square, Shiraz, Fars, Iran
City
Shiraz
Province
Fars
Postal code
7193613311
Phone
+98 71 3647 4332
Email
rahimijaberia@gmail.com

12

Recruitment center
Name of recruitment center
Emam Reza hospital
Full name of responsible person
Dr Hormoz Ayromlouh; Dr Mohammad Yazdchi Marandi
Street address
Golgasht St.
City
Tabriz
Province
West Azarbaijan
Postal code
5166614756
Phone
+98 41 3335 2073
Email
ayromlouh@gmail.com

Sponsors / Funding sources

1

Sponsor
Name of organization / entity
AryoGen Pharmed Co.
Full name of responsible person
Nassim Anjidani
Street address
Cross Tajbakhsh Street, 24th Kilometer Makhsous.
City
Garm Darreh
Province
Alborz
Postal code
56145226
Phone
+98 26 3610 6480
Email
contact@aryogen.com
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
AryoGen Pharmed Co.
Proportion provided by this source
100
Public or private sector
Private
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Industry

Person responsible for general inquiries

Contact
Name of organization / entity
Orchid Pharmed Co.
Full name of responsible person
Nassim Anjidani
Position
Medical Department Manager
Latest degree
Medical doctor
Other areas of specialty/work
Medical Pharmacy
Street address
No 42, Attar St., Vanak Sq.
City
Tehran
Province
Tehran
Postal code
1994766411
Phone
009843473000
Email
anjidani.n@orchipharmed.com

Person responsible for scientific inquiries

Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Dr. Farzad Fatehi
Position
Associate professor
Latest degree
Subspecialist
Other areas of specialty/work
Neurology
Street address
Shariati hospital, Cross Jalal Al Ahmad highway, North Karegar St.
City
Tehran
Province
Tehran
Postal code
1411713135
Phone
+98 21 8490 1000
Email
fatehifa@gmail.com

Person responsible for updating data

Contact
Name of organization / entity
Orchid Pharmed Co.
Full name of responsible person
Nassim Anjidani
Position
Medical Department Manager
Latest degree
Medical doctor
Other areas of specialty/work
Medical Pharmacy
Street address
No 42, Attar Neyshaboori St., Vanak Sq.
City
Tehran
Province
Tehran
Postal code
1994766411
Phone
+98 21 4347 3000
Email
anjidani.n@orchidpharmed.com

Sharing plan

Deidentified Individual Participant Data Set (IPD)
Undecided - It is not yet known if there will be a plan to make this available
Study Protocol
Undecided - It is not yet known if there will be a plan to make this available
Statistical Analysis Plan
Undecided - It is not yet known if there will be a plan to make this available
Informed Consent Form
Undecided - It is not yet known if there will be a plan to make this available
Clinical Study Report
Undecided - It is not yet known if there will be a plan to make this available
Analytic Code
Undecided - It is not yet known if there will be a plan to make this available
Data Dictionary
Undecided - It is not yet known if there will be a plan to make this available
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