Trial Outcomes & Findings for Efficacy and Safety of GTR in Comparison to Copaxone® (NCT NCT01489254)

Last Updated: 2016-12-29

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

794 participants

Primary outcome timeframe

9 months

Results posted on

2016-12-29

Participant Flow

Subjects were randomized at 118 investigational sites in 17 countries.

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.

Participant milestones

Participant milestones
Measure	Glatiramer 20 mg Glatiramer Acetate (GTR) 20 mg daily for 9 months	Copaxone 20 mg Glatiramer Acetate (Copaxone) 20 mg daily for 9 months	Placebo Placebo (daily) for 9 months	Extension Glatiramer 20 mg Glatiramer acetate (GTR) 20 mg daily for 15 months, open-label extension
Double-blind Part STARTED	355	357	84	0
Double-blind Part COMPLETED	330	324	81	0
Double-blind Part NOT COMPLETED	25	33	3	0
Open-label Extension Part STARTED	0	0	0	728
Open-label Extension Part COMPLETED	0	0	0	670
Open-label Extension Part NOT COMPLETED	0	0	0	58

Reasons for withdrawal

Reasons for withdrawal
Measure	Glatiramer 20 mg Glatiramer Acetate (GTR) 20 mg daily for 9 months	Copaxone 20 mg Glatiramer Acetate (Copaxone) 20 mg daily for 9 months	Placebo Placebo (daily) for 9 months	Extension Glatiramer 20 mg Glatiramer acetate (GTR) 20 mg daily for 15 months, open-label extension
Double-blind Part Adverse Event	7	2	2	0
Double-blind Part Pregnancy	1	3	0	0
Double-blind Part Withdrawal by Subject	12	20	1	0
Double-blind Part Lost to Follow-up	1	2	0	0
Double-blind Part Other reasons for not completing study	4	6	0	0
Open-label Extension Part Adverse Event	0	0	0	10
Open-label Extension Part Pregnancy	0	0	0	3
Open-label Extension Part Withdrawal by Subject	0	0	0	30
Open-label Extension Part Protocol Violation	0	0	0	1
Open-label Extension Part Lost to Follow-up	0	0	0	9
Open-label Extension Part Other reasons for not completing study	0	0	0	5

Baseline Characteristics

Efficacy and Safety of GTR in Comparison to Copaxone®

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Glatiramer 20 mg n=353 Participants Glatiramer Acetate (GTR) 20 mg daily for 9 months	Copaxone 20 mg n=357 Participants Glatiramer Acetate (Copaxone) 20 mg daily for 9 months	Placebo n=84 Participants Placebo (daily) for 9 months	Total n=794 Participants Total of all reporting groups
Age, Continuous	32.6 years STANDARD_DEVIATION 8.6 • n=5 Participants	33.8 years STANDARD_DEVIATION 9.0 • n=7 Participants	32.6 years STANDARD_DEVIATION 8.7 • n=5 Participants	33.1 years STANDARD_DEVIATION 8.8 • n=4 Participants
Gender Female	233 Participants n=5 Participants	238 Participants n=7 Participants	57 Participants n=5 Participants	528 Participants n=4 Participants
Gender Male	120 Participants n=5 Participants	119 Participants n=7 Participants	27 Participants n=5 Participants	266 Participants n=4 Participants
Time from first clinical event to randomization	5.5 years STANDARD_DEVIATION 5.3 • n=5 Participants	6.4 years STANDARD_DEVIATION 6.0 • n=7 Participants	5.7 years STANDARD_DEVIATION 6.0 • n=5 Participants	5.9 years STANDARD_DEVIATION 5.7 • n=4 Participants
Number of relapses in period within 2 year prior to signing ICF	1.9 Number of relapses STANDARD_DEVIATION 0.9 • n=5 Participants	1.8 Number of relapses STANDARD_DEVIATION 0.9 • n=7 Participants	1.9 Number of relapses STANDARD_DEVIATION 0.9 • n=5 Participants	1.8 Number of relapses STANDARD_DEVIATION 0.9 • n=4 Participants

PRIMARY outcome

Timeframe: 9 months

Population: Full Analyis Set (FAS): all randomized subjects who received at least 1 dose of trial medication

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.

Outcome measures

Outcome measures
Measure	Glatiramer 20 mg n=353 Participants Glatiramer Acetate (GTR) 20 mg daily for 9 months	Copaxone 20 mg n=357 Participants Glatiramer Acetate (Copaxone) 20 mg daily for 9 months	Placebo n=84 Participants Placebo (daily) for 9 months
The Number of T1-Gadolinium Enhancing Lesions During Months 7-9 Sensitivity analysis - Number of Gd lesions	0.42 Number of lesions Interval 0.31 to 0.57	0.38 Number of lesions Interval 0.28 to 0.52	0.82 Number of lesions Interval 0.57 to 1.2
The Number of T1-Gadolinium Enhancing Lesions During Months 7-9 Equivalence analysis - Number of Gd lesions	0.45 Number of lesions Interval 0.34 to 0.59	0.41 Number of lesions Interval 0.31 to 0.54	—

Adverse Events

Glatiramer 20 mg

Serious events: 12 serious events

Other events: 110 other events

Deaths: 0 deaths

Copaxone 20 mg

Serious events: 17 serious events

Other events: 121 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 29 other events

Deaths: 0 deaths

Extension Glatiramer 20 mg

Serious events: 22 serious events

Other events: 90 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Glatiramer 20 mg n=353 participants at risk Glatiramer Acetate (GTR) 20 mg daily for 9 months, double-blind	Copaxone 20 mg n=357 participants at risk Glatiramer Acetate (Copaxone) 20 mg daily for 9 months, double-blind	Placebo n=84 participants at risk Placebo (daily) for 9 months, double-blind	Extension Glatiramer 20 mg n=728 participants at risk Glatiramer acetate (GTR) 20 mg daily for 15 months, open-label extension
General disorders Injection site reaction	16.4% 58/353 • 9 months + 15 months The safety population consisted of all subjects who received at least 1 injection with study treatment.	17.4% 62/357 • 9 months + 15 months The safety population consisted of all subjects who received at least 1 injection with study treatment.	7.1% 6/84 • 9 months + 15 months The safety population consisted of all subjects who received at least 1 injection with study treatment.	2.1% 15/728 • 9 months + 15 months The safety population consisted of all subjects who received at least 1 injection with study treatment.
General disorders Immediate post-injection reaction	6.8% 24/353 • 9 months + 15 months The safety population consisted of all subjects who received at least 1 injection with study treatment.	4.8% 17/357 • 9 months + 15 months The safety population consisted of all subjects who received at least 1 injection with study treatment.	0.00% 0/84 • 9 months + 15 months The safety population consisted of all subjects who received at least 1 injection with study treatment.	1.5% 11/728 • 9 months + 15 months The safety population consisted of all subjects who received at least 1 injection with study treatment.
General disorders Injection site swelling	4.0% 14/353 • 9 months + 15 months The safety population consisted of all subjects who received at least 1 injection with study treatment.	3.4% 12/357 • 9 months + 15 months The safety population consisted of all subjects who received at least 1 injection with study treatment.	3.6% 3/84 • 9 months + 15 months The safety population consisted of all subjects who received at least 1 injection with study treatment.	0.55% 4/728 • 9 months + 15 months The safety population consisted of all subjects who received at least 1 injection with study treatment.
General disorders Injection site pain	3.1% 11/353 • 9 months + 15 months The safety population consisted of all subjects who received at least 1 injection with study treatment.	3.6% 13/357 • 9 months + 15 months The safety population consisted of all subjects who received at least 1 injection with study treatment.	1.2% 1/84 • 9 months + 15 months The safety population consisted of all subjects who received at least 1 injection with study treatment.	0.96% 7/728 • 9 months + 15 months The safety population consisted of all subjects who received at least 1 injection with study treatment.
General disorders Injection site haematoma	0.28% 1/353 • 9 months + 15 months The safety population consisted of all subjects who received at least 1 injection with study treatment.	0.00% 0/357 • 9 months + 15 months The safety population consisted of all subjects who received at least 1 injection with study treatment.	3.6% 3/84 • 9 months + 15 months The safety population consisted of all subjects who received at least 1 injection with study treatment.	0.00% 0/728 • 9 months + 15 months The safety population consisted of all subjects who received at least 1 injection with study treatment.
General disorders Injection site bruising	0.00% 0/353 • 9 months + 15 months The safety population consisted of all subjects who received at least 1 injection with study treatment.	0.00% 0/357 • 9 months + 15 months The safety population consisted of all subjects who received at least 1 injection with study treatment.	3.6% 3/84 • 9 months + 15 months The safety population consisted of all subjects who received at least 1 injection with study treatment.	0.14% 1/728 • 9 months + 15 months The safety population consisted of all subjects who received at least 1 injection with study treatment.
Infections and infestations Nasopharyngitis	3.7% 13/353 • 9 months + 15 months The safety population consisted of all subjects who received at least 1 injection with study treatment.	6.4% 23/357 • 9 months + 15 months The safety population consisted of all subjects who received at least 1 injection with study treatment.	7.1% 6/84 • 9 months + 15 months The safety population consisted of all subjects who received at least 1 injection with study treatment.	5.4% 39/728 • 9 months + 15 months The safety population consisted of all subjects who received at least 1 injection with study treatment.
Infections and infestations Upper respiratory tract infection	1.7% 6/353 • 9 months + 15 months The safety population consisted of all subjects who received at least 1 injection with study treatment.	1.7% 6/357 • 9 months + 15 months The safety population consisted of all subjects who received at least 1 injection with study treatment.	3.6% 3/84 • 9 months + 15 months The safety population consisted of all subjects who received at least 1 injection with study treatment.	0.69% 5/728 • 9 months + 15 months The safety population consisted of all subjects who received at least 1 injection with study treatment.
Infections and infestations Respiratory tract infection	0.57% 2/353 • 9 months + 15 months The safety population consisted of all subjects who received at least 1 injection with study treatment.	1.1% 4/357 • 9 months + 15 months The safety population consisted of all subjects who received at least 1 injection with study treatment.	4.8% 4/84 • 9 months + 15 months The safety population consisted of all subjects who received at least 1 injection with study treatment.	0.55% 4/728 • 9 months + 15 months The safety population consisted of all subjects who received at least 1 injection with study treatment.
Nervous system disorders Headache	4.5% 16/353 • 9 months + 15 months The safety population consisted of all subjects who received at least 1 injection with study treatment.	3.4% 12/357 • 9 months + 15 months The safety population consisted of all subjects who received at least 1 injection with study treatment.	8.3% 7/84 • 9 months + 15 months The safety population consisted of all subjects who received at least 1 injection with study treatment.	2.2% 16/728 • 9 months + 15 months The safety population consisted of all subjects who received at least 1 injection with study treatment.

Additional Information

VP Clinical Development

Synthon BV

Phone: +3124727700

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER