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Efficacy and Safety of GTR in Comparison to Copaxone® (GATE)

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ClinicalTrials.gov Identifier: NCT01489254
Recruitment Status : Completed
First Posted : December 9, 2011
Results First Posted : October 31, 2016
Last Update Posted : December 29, 2016
Sponsor:
Information provided by (Responsible Party):
Synthon BV

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Multiple Sclerosis
Interventions Drug: Glatiramer Acetate (GTR)
Drug: Glatiramer Acetate (Copaxone®)
Drug: Placebo
Enrollment 794
Recruitment Details Subjects were randomized at 118 investigational sites in 17 countries.
Pre-assignment Details 1549 patients were assessed for eligibility of whom 796 subjects were randomized in a 4.3:4.3:1 ratio to receive generic glatiramer acetate (GTR), brand glatiramer acetate (Copaxone) or matching placebo. Two subjects were randomized to the generic glatiramer acetate group but did not start treatment and were not enrolled.
Arm/Group Title Glatiramer 20 mg Copaxone 20 mg Placebo Extension Glatiramer 20 mg
Hide Arm/Group Description Glatiramer Acetate (GTR) 20 mg daily for 9 months Glatiramer Acetate (Copaxone) 20 mg daily for 9 months Placebo (daily) for 9 months Glatiramer acetate (GTR) 20 mg daily for 15 months, open-label extension
Period Title: Double-blind Part
Started 355 357 84 0
Completed 330 324 81 0
Not Completed 25 33 3 0
Reason Not Completed
Adverse Event             7             2             2             0
Pregnancy             1             3             0             0
Withdrawal by Subject             12             20             1             0
Lost to Follow-up             1             2             0             0
Other reasons for not completing study             4             6             0             0
Period Title: Open-label Extension Part
Started 0 0 0 728 [1]
Completed 0 0 0 670
Not Completed 0 0 0 58
Reason Not Completed
Adverse Event             0             0             0             10
Pregnancy             0             0             0             3
Withdrawal by Subject             0             0             0             30
Protocol Violation             0             0             0             1
Lost to Follow-up             0             0             0             9
Other reasons for not completing study             0             0             0             5
[1]
735 completed the DB part, 729 were eligible to continue in the OL part, 1 opted not to continue
Arm/Group Title Glatiramer 20 mg Copaxone 20 mg Placebo Total
Hide Arm/Group Description Glatiramer Acetate (GTR) 20 mg daily for 9 months Glatiramer Acetate (Copaxone) 20 mg daily for 9 months Placebo (daily) for 9 months Total of all reporting groups
Overall Number of Baseline Participants 353 357 84 794
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 353 participants 357 participants 84 participants 794 participants
32.6  (8.6) 33.8  (9.0) 32.6  (8.7) 33.1  (8.8)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 353 participants 357 participants 84 participants 794 participants
Female
233
  66.0%
238
  66.7%
57
  67.9%
528
  66.5%
Male
120
  34.0%
119
  33.3%
27
  32.1%
266
  33.5%
Time from first clinical event to randomization  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 353 participants 357 participants 84 participants 794 participants
5.5  (5.3) 6.4  (6.0) 5.7  (6.0) 5.9  (5.7)
Number of relapses in period within 2 year prior to signing ICF  
Mean (Standard Deviation)
Unit of measure:  Number of relapses
Number Analyzed 353 participants 357 participants 84 participants 794 participants
1.9  (0.9) 1.8  (0.9) 1.9  (0.9) 1.8  (0.9)
1.Primary Outcome
Title The Number of T1-Gadolinium Enhancing Lesions During Months 7-9
Hide Description The primary endpoint was the total number of gadolinium enhancing lesions (i.e., the cumulative number of new and persisting gadolinium enhancing lesions) during months 7 through 9.
Time Frame 9 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analyis Set (FAS): all randomized subjects who received at least 1 dose of trial medication
Arm/Group Title Glatiramer 20 mg Copaxone 20 mg Placebo
Hide Arm/Group Description:
Glatiramer Acetate (GTR) 20 mg daily for 9 months
Glatiramer Acetate (Copaxone) 20 mg daily for 9 months
Placebo (daily) for 9 months
Overall Number of Participants Analyzed 353 357 84
Mean (95% Confidence Interval)
Unit of Measure: Number of lesions
Sensitivity analysis - Number of Gd lesions Number Analyzed 353 participants 357 participants 84 participants
0.42
(0.31 to 0.57)
0.38
(0.28 to 0.52)
0.82
(0.57 to 1.20)
Equivalence analysis - Number of Gd lesions Number Analyzed 353 participants 357 participants 0 participants
0.45
(0.34 to 0.59)
0.41
(0.31 to 0.54)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Glatiramer 20 mg, Copaxone 20 mg, Placebo
Comments Estimates represent the mean total lesions during months 7 through 9 and were estimated from the fitted random effect generalized linear model (longitudinal model) with a negative binomial distribution and logaritmic link function. To assess study sensitivity, data of the active treatment groups and placebo were included in the model, resulting in the ratios and 95% CIs for the combined Glatiramer 20 mg and Copaxone 20 mg treatment group and the individual treatments over placebo.
Type of Statistical Test Non-Inferiority or Equivalence
Comments To conclude study sensitivity the combined active treatment groups Glatiramer 20 mg and Copaxone 20 mg needed to be superior to placebo.
Method of Estimation Estimation Parameter Ratio (or Ratio of estimated means)
Estimated Value 0.488
Confidence Interval (2-Sided) 95%
0.365 to 0.651
Estimation Comments Ratio of combined Glatiramer 20 mg + Copaxone 20 mg to placebo and 95% confidence interval.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Glatiramer 20 mg, Copaxone 20 mg
Comments Estimates represent the mean total lesions during months 7 through 9 and were estimated from the fitted random effect generalized linear model (longitudinal model) with a negative binomial distribution and logaritmic link function including Glatiramer 20 mg and Copaxone 20 mg treatment groups to assess study equivalence.
Type of Statistical Test Non-Inferiority or Equivalence
Comments To conclude equivalence between Glatiramer 20 mg and Copaxone 20 mg, efficacy in the combined active treatment groups needed to be superior to placebo (confirming study sensitivity) and the 2-sided 95% CI for the estimated ratio of Glatiramer 20 mg to Copaxone 20 mg needed to be fully enclosed in the prespecified equivalence margin (0.727 - 1.375).
Method of Estimation Estimation Parameter Ratio (or Ratio of estimated means)
Estimated Value 1.095
Confidence Interval (2-Sided) 95%
0.883 to 1.360
Estimation Comments Ratio of Glatiramer 20 mg to Copaxone 20 mg and 95% confidence interval.
Time Frame 9 months + 15 months
Adverse Event Reporting Description The safety population consisted of all subjects who received at least 1 injection with study treatment.
 
Arm/Group Title Glatiramer 20 mg Copaxone 20 mg Placebo Extension Glatiramer 20 mg
Hide Arm/Group Description Glatiramer Acetate (GTR) 20 mg daily for 9 months, double-blind Glatiramer Acetate (Copaxone) 20 mg daily for 9 months, double-blind Placebo (daily) for 9 months, double-blind Glatiramer acetate (GTR) 20 mg daily for 15 months, open-label extension
All-Cause Mortality
Glatiramer 20 mg Copaxone 20 mg Placebo Extension Glatiramer 20 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Glatiramer 20 mg Copaxone 20 mg Placebo Extension Glatiramer 20 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   12/353 (3.40%)   17/357 (4.76%)   2/84 (2.38%)   22/728 (3.02%) 
Eye disorders         
Uveitis   0/353 (0.00%)  0/357 (0.00%)  0/84 (0.00%)  1/728 (0.14%) 
Gastrointestinal disorders         
Constipation   0/353 (0.00%)  1/357 (0.28%)  0/84 (0.00%)  0/728 (0.00%) 
Pancreatitis acute   0/353 (0.00%)  0/357 (0.00%)  0/84 (0.00%)  1/728 (0.14%) 
General disorders         
Immediate post-injection reaction   0/353 (0.00%)  1/357 (0.28%)  0/84 (0.00%)  0/728 (0.00%) 
Hepatobiliary disorders         
Hepatitis toxic   1/353 (0.28%)  0/357 (0.00%)  0/84 (0.00%)  0/728 (0.00%) 
Cholecystitis   0/353 (0.00%)  0/357 (0.00%)  0/84 (0.00%)  1/728 (0.14%) 
Immune system disorders         
Anaphylactoid reaction   1/353 (0.28%)  1/357 (0.28%)  0/84 (0.00%)  0/728 (0.00%) 
Hypersensitivity   1/353 (0.28%)  0/357 (0.00%)  0/84 (0.00%)  0/728 (0.00%) 
Anaphylactic reaction   0/353 (0.00%)  0/357 (0.00%)  0/84 (0.00%)  1/728 (0.14%) 
Infections and infestations         
Pneumonia   1/353 (0.28%)  0/357 (0.00%)  0/84 (0.00%)  0/728 (0.00%) 
Respiratory tract infection viral   1/353 (0.28%)  0/357 (0.00%)  0/84 (0.00%)  0/728 (0.00%) 
Bronchitis   0/353 (0.00%)  2/357 (0.56%)  0/84 (0.00%)  0/728 (0.00%) 
Peritonitis   0/353 (0.00%)  1/357 (0.28%)  0/84 (0.00%)  0/728 (0.00%) 
Salpingo-oophoritis   0/353 (0.00%)  0/357 (0.00%)  1/84 (1.19%)  0/728 (0.00%) 
Varicella   0/353 (0.00%)  1/357 (0.28%)  0/84 (0.00%)  0/728 (0.00%) 
Appendicitis   0/353 (0.00%)  0/357 (0.00%)  0/84 (0.00%)  1/728 (0.14%) 
Injury, poisoning and procedural complications         
Tibia fracture   1/353 (0.28%)  0/357 (0.00%)  0/84 (0.00%)  0/728 (0.00%) 
Brain contusion   0/353 (0.00%)  1/357 (0.28%)  0/84 (0.00%)  0/728 (0.00%) 
Fibula fracture   1/353 (0.28%)  0/357 (0.00%)  0/84 (0.00%)  0/728 (0.00%) 
Joint dislocation   0/353 (0.00%)  0/357 (0.00%)  0/84 (0.00%)  2/728 (0.27%) 
Musculoskeletal and connective tissue disorders         
Osteoarthritis   0/353 (0.00%)  0/357 (0.00%)  0/84 (0.00%)  1/728 (0.14%) 
Patellofemoral pain syndrome   0/353 (0.00%)  0/357 (0.00%)  0/84 (0.00%)  1/728 (0.14%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Metastases to central nervous sytem   1/353 (0.28%)  0/357 (0.00%)  0/84 (0.00%)  0/728 (0.00%) 
Uterine leiomyoma   1/353 (0.28%)  0/357 (0.00%)  0/84 (0.00%)  2/728 (0.27%) 
Glioblastoma multiforme   0/353 (0.00%)  1/357 (0.28%)  0/84 (0.00%)  0/728 (0.00%) 
Benign hydatidiform mole   0/353 (0.00%)  0/357 (0.00%)  0/84 (0.00%)  1/728 (0.14%) 
Small intestine carcinoma   0/353 (0.00%)  0/357 (0.00%)  0/84 (0.00%)  1/728 (0.14%) 
Nervous system disorders         
Multiple sclerosis relapse   2/353 (0.57%)  4/357 (1.12%)  0/84 (0.00%)  5/728 (0.69%) 
Epilepsy   0/353 (0.00%)  1/357 (0.28%)  0/84 (0.00%)  0/728 (0.00%) 
Sciatica   0/353 (0.00%)  1/357 (0.28%)  0/84 (0.00%)  0/728 (0.00%) 
Status epilepticus   0/353 (0.00%)  1/357 (0.28%)  0/84 (0.00%)  0/728 (0.00%) 
Radiculitis cervical   0/353 (0.00%)  0/357 (0.00%)  0/84 (0.00%)  1/728 (0.14%) 
Secondary progressive multiple sclerosis   0/353 (0.00%)  0/357 (0.00%)  0/84 (0.00%)  1/728 (0.14%) 
Psychiatric disorders         
Depression   1/353 (0.28%)  0/357 (0.00%)  0/84 (0.00%)  0/728 (0.00%) 
Anxiety   0/353 (0.00%)  1/357 (0.28%)  0/84 (0.00%)  0/728 (0.00%) 
Bipolar disorder   0/353 (0.00%)  1/357 (0.28%)  0/84 (0.00%)  0/728 (0.00%) 
Renal and urinary disorders         
Urinary retention   0/353 (0.00%)  1/357 (0.28%)  0/84 (0.00%)  0/728 (0.00%) 
Renal colic   0/353 (0.00%)  0/357 (0.00%)  0/84 (0.00%)  1/728 (0.14%) 
Nephrolithiasis   0/353 (0.00%)  0/357 (0.00%)  0/84 (0.00%)  1/728 (0.14%) 
Reproductive system and breast disorders         
Ovarian cyst ruptured   0/353 (0.00%)  0/357 (0.00%)  1/84 (1.19%)  0/728 (0.00%) 
Endometriosis   0/353 (0.00%)  0/357 (0.00%)  0/84 (0.00%)  1/728 (0.14%) 
Ovarian cyst   0/353 (0.00%)  0/357 (0.00%)  0/84 (0.00%)  1/728 (0.14%) 
Skin and subcutaneous tissue disorders         
Angioedema   1/353 (0.28%)  1/357 (0.28%)  0/84 (0.00%)  1/728 (0.14%) 
Psoriasis   0/353 (0.00%)  0/357 (0.00%)  0/84 (0.00%)  1/728 (0.14%) 
Surgical and medical procedures         
Abortion induced   0/353 (0.00%)  1/357 (0.28%)  0/84 (0.00%)  0/728 (0.00%) 
Vascular disorders         
Peripheral artery thrombosis   0/353 (0.00%)  0/357 (0.00%)  0/84 (0.00%)  1/728 (0.14%) 
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
Glatiramer 20 mg Copaxone 20 mg Placebo Extension Glatiramer 20 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   110/353 (31.16%)   121/357 (33.89%)   29/84 (34.52%)   90/728 (12.36%) 
General disorders         
Injection site reaction   58/353 (16.43%)  62/357 (17.37%)  6/84 (7.14%)  15/728 (2.06%) 
Immediate post-injection reaction   24/353 (6.80%)  17/357 (4.76%)  0/84 (0.00%)  11/728 (1.51%) 
Injection site swelling   14/353 (3.97%)  12/357 (3.36%)  3/84 (3.57%)  4/728 (0.55%) 
Injection site pain   11/353 (3.12%)  13/357 (3.64%)  1/84 (1.19%)  7/728 (0.96%) 
Injection site haematoma   1/353 (0.28%)  0/357 (0.00%)  3/84 (3.57%)  0/728 (0.00%) 
Injection site bruising   0/353 (0.00%)  0/357 (0.00%)  3/84 (3.57%)  1/728 (0.14%) 
Infections and infestations         
Nasopharyngitis   13/353 (3.68%)  23/357 (6.44%)  6/84 (7.14%)  39/728 (5.36%) 
Upper respiratory tract infection   6/353 (1.70%)  6/357 (1.68%)  3/84 (3.57%)  5/728 (0.69%) 
Respiratory tract infection   2/353 (0.57%)  4/357 (1.12%)  4/84 (4.76%)  4/728 (0.55%) 
Nervous system disorders         
Headache   16/353 (4.53%)  12/357 (3.36%)  7/84 (8.33%)  16/728 (2.20%) 
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Synthon's agreements with its investigators may vary. However, Synthon BV does not prohibit any investigator from publishing. Any publication from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: VP Clinical Development
Organization: Synthon BV
Phone: +3124727700
EMail: clinicaltrials@synthon.com
Layout table for additonal information
Responsible Party: Synthon BV
ClinicalTrials.gov Identifier: NCT01489254     History of Changes
Other Study ID Numbers: GTR001
2011-000888-27 ( EudraCT Number )
First Submitted: December 8, 2011
First Posted: December 9, 2011
Results First Submitted: April 18, 2016
Results First Posted: October 31, 2016
Last Update Posted: December 29, 2016