Efficacy and safety of peginterferon beta-1a (CinnaGen®) versus CinnoVex (CinnaGen ®) in reducing the annualized relapse rate (ARR) in participants with relapsing-remitting multiple sclerosis: A phase III, randomized, parallel, non-inferiority study
The study is designed as phase III, randomized, two armed, multicenter, parallel, active controlled non inferiority clinical trial to investigate the efficacy and safety of peginterferon beta-1a (CinnaGen®) versus CinnoVex (CinnaGen ®) in reducing the annualized relapse rate (ARR) in participants with relapsing-remitting multiple sclerosis.
Participants include patients aged 18-50 years; Relapsing-remitting multiple sclerosis (McDonald criteria 2010); Expanded Disability Status Scale is 0–5 (described in details in eligibility criteria section below)
In intervention group: Pegylated interferon beta-1a (CinnaGen®) prefilled syringe for patients with dose of 125micrograms, subcutaneous (S/C) injection every 2weeks for 24 months
In control group: CinnoVex (CinnaGen ®) 30 mcg injected intramuscularly once a week for 24 months.
Primary outcomes: Annual relapse rate; Secondary outcomes: Number of new or newly enlarging hyperintense lesions on T2-weighted images (relative to baseline MRI), proportion of patients with12 weeks of sustained disability progression. MRI endpoints: Number of gadolinium enhancing lesions, New T1 hypointense lesions, New active lesions (sum of gadolinium-enhancing plus non-enhancing new or newly enlarging T2 hyper intense lesions),Volume of new or newly enlarging T2 hyperintense, gadolinium-enhancing, and T1 hypointense lesions, brain atrophy. The primary and secondary outcomes will be assessed at 24 months of the study.
General information
Acronym
IRCT registration information
IRCT registration number:IRCT201612306135N8
Registration date:2017-01-14, 1395/10/25
Registration timing:prospective
Last update:
Update count:3
Registration date
2017-01-14, 1395/10/25
Registrant information
Name
Hamed Hosseini
Name of organization / entity
Clinical Trial Center (CTC),Tehran University of Medical Sciences (TUMS)
Country
Iran (Islamic Republic of)
Phone
+98 21 8896 3546
Email address
hhosseini@sina.tums.ac.ir
Recruitment status
Recruitment complete
Funding source
CinnaGen Pharmaceutical Company
Expected recruitment start date
2017-02-28, 1395/12/10
Expected recruitment end date
2018-05-31, 1397/03/10
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Efficacy and safety of peginterferon beta-1a (CinnaGen®) versus CinnoVex (CinnaGen ®) in reducing the annualized relapse rate (ARR) in participants with relapsing-remitting multiple sclerosis: A phase III, randomized, parallel, non-inferiority study
Public title
Efficacy and safety of peginterferon beta-1a (CinnaGen®) in relapsing-remitting multiple sclerosis patients
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria: Age 18-50 years ; Relapsing-remitting multiple sclerosis (McDonald criteria 2010); Expanded Disability Status Scale is 0–5 ; At least two clinically documented relapses in the previous 3 years; At least one relapse having occurred within the past 12 months; Subjects have refused alternative treatments and other available therapies; Ability to understand the purpose and risks of the study and provide signed and dated informed consent; Negative pregnancy test for childbearing women.
Exclusion criteria:
• • Primary progressive, secondary progressive, or progressive relapsing MS
• Female subjects considering becoming pregnant while in the study or currently breastfeeding
• Subjects for whom MRI was contraindicated, i.e., who had pacemakers or other contraindicated implanted metal devices, were allergic to gadolinium, or had claustrophobia that could not be medically managed.
• Unwillingness or inability to comply with the requirements of the protocol including the presence of any condition (physical, mental or social) that was likely to affect the subject’s ability to comply with the protocol.
• Pre-specified laboratory abnormalities
• History of any clinically significant (as determined by the Investigator) cardiac,
endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, and renal, or other major disease that would preclude participation in a clinical trial.
• History of malignant disease, including solid tumors and hematologic malignancies (with the exception of basal cell and squamous cell carcinomas of the skin that have been completely excised and are considered cured).
• History of seizure disorder or unexplained blackouts OR history of a seizure within 3 months prior to Baseline.
• History of suicidal ideation within 3 months prior to Baseline or an episode of severe depression within 3 months prior to Baseline. Severe depression is defined as an episode of depression that requires hospitalization, or at the discretion of the Investigator.
• Abnormal screening blood tests exceeding any of the limits defined below:
- Alanine transaminase/serum glutamate pyruvate transaminase (ALT/SGPT) greater than 2 times the upper limit of normal (>2 × ULN) or aspartate transaminase/serum glutamic oxaloacetic transaminase (AST/SGOT) >2 × ULN or bilirubin >1.5 × ULN.
- Total white blood cell count (WBC) <4000 /mm3
- Absolute Neutrophil Count (ANC) of < 1500 /mm3
- Platelet count <120,000 c/mm3
- Hemoglobin <10 g/dL in female subjects; <11 g/dL in male subjects
- Serum creatinine> upper limit of normal lab value
• A MS relapse that has occurred within the 30 days prior to randomization and/or the subject has not stabilized from a previous relapse prior to randomization (Day 1).
• Elective surgery performed from 2 weeks prior to randomization (Day 1) or scheduled through the end of the study.
• Treatment with other agents to treat MS symptoms or underlying disease as specified below:
• Any prior treatment with:
– Total Lymphoid Irradiation
– Cladribine
– T-cell Vaccine
– Natalizumab
– Rituximab
– BIIB017
• Prior treatment within 1 year of randomization:
– Cyclophosphamide
– Mitoxantrone
• Prior treatment within 6 months prior to randomization:
– Cyclosporine
– Plasma exchange
– Intravenous immunoglobulin (IVIG)
– Azathioprine
– Methotrexate
• Subjects must have discontinued interferon treatment 6 months prior to randomization
• Prior treatment within 30 days prior to randomization
– Systemic corticosteroids
• Prior treatment with glatiramer acetate within 4 weeks prior to randomization
• Treatment with another investigational drug or approved therapy for investigational use within the 6 months prior to randomization.
• Other unspecified reasons that, in the opinion of the investigator, made the subject unsuitable for enrolment
Ralapse rate counts during 24 months/ monthly visits
Method of measurement
Episodes when there are exacerbations of symptoms
Secondary outcomes
1
Description
Number of new or newly enlarging hyperintense lesions on T2-weighted images (relative to baseline MRI)
Timepoint
Baseline, 6th , 12th, 24th month
Method of measurement
MRI evaluation
2
Description
Proportion of patients with 12 weeks of sustained disability progression
Timepoint
During 24 months of study follow up
Method of measurement
Clinial evaluation
3
Description
Gadolinium enhancing lesions, New active lesions (t2), - Volume of new or newly enlarging T2 hyperintense, gadolinium-enhancing, and T1 hypointense lesions, brain atrophy
Timepoint
6th , 12th, 24th month
Method of measurement
MRI evaluation
4
Description
Any - Adverse events (AEs), Adverse drug reactions (ADR) including: o Flu like symptoms, injection site reaction (redness, pain, itching, necrosis), o Rising AST, ALT or ALP 2.5 times more than normal value,o Hyperbilirubinemia: 1.5 Times more than normal value, Leukopenia (WBC <3000), Thrombocytopenia (Platelet count < 100,000),..
Timepoint
During 24 months of study follow up
Method of measurement
Clinial and laboratory evaluation
Intervention groups
1
Description
Pegylated interferon beta-1a (CinnaGen) autoinjector (Physioject™) for patients with dose of 125micrograms, subcutaneous (S/C) injection every 2weeks for 24 months
Category
Treatment - Drugs
2
Description
CinnoVex® (CinnaGen) 30 mcg, prefilled syringe, injected intramuscularly once a week for 24 months.
Category
Treatment - Drugs
Recruitment centers
1
Recruitment center
Name of recruitment center
MS research center, Sina Hospital, Tehran
Full name of responsible person
Dr. Amir Reza Azimi, Dr. Mohammad Ali Sahraiean, Dr. Abdolreza Naser Moghadasi
Street address
MS Research Center, Sina Hospital, Hasan Abad Square- Emam Khomeyni Street, Tehran
City
Tehran
2
Recruitment center
Name of recruitment center
Amir Alam Hospital
Full name of responsible person
Dr. Roya Abolfazli
Street address
Amir Alam Hospital, Saadi Street, Enghelab Street, Tehran
City
Tehran
3
Recruitment center
Name of recruitment center
Emam Hossein Hospital
Full name of responsible person
Dr. Nahid Beladi Moghadam
Street address
Emam Hossein Hospital, Shahid Madani Street, Tehran
City
Tehran
4
Recruitment center
Name of recruitment center
MS clinic – Ayatolah Kashani Hospital
Full name of responsible person
Dr. Vahid Shaygannezhad, Dr. Fereshreh Ashtari
Street address
MS clinic, Ayatolah Kashani Hospital, Ayatolah Kashani Street, Isfahan
City
Isfahan
5
Recruitment center
Name of recruitment center
Ghaem Hospital
Full name of responsible person
Dr. Morteza Saiedi
Street address
Ghaem Hospital- Parastar Street- Ahmad Abad Street- Mashhad
City
Mashhad
6
Recruitment center
Name of recruitment center
MS clinic – Bou ali Hospital
Full name of responsible person
Dr. Mohammd Baghbanian
Street address
MS clinic – Bou ali Hospital- Pasdaran Boulevard- Sari