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SUPPLEMENTARY DIGITAL CONTENT
Supplementary Table. Overview of the Completed Studies of Intravitreal Ocriplasmin (completed as of July 24, 2013)
Study ID Design/Control Eye condition Single intravitreal injection:
dose/time before vitrectomy (if applicable)
Number of patients (entered treatment)
Duration
a
Phase III placebo-controlled studies Ocriplasmin 125 μg
Placebo
465 187 MIVI-TRUST
(TG-MV-006) NCT0078185915
Phase III multicenter, randomized, placebo-controlled, double-masked study in patients with symptomatic VMA (i.e. focal VMA leading to symptoms) conducted in US
Symptomatic VMA ocriplasmin 125 μg placebo
220b,c 106
6 months
MIVI-TRUST (TG-MV-007) NCT0079831715
Phase III multicenter, randomized, placebo-controlled, double-masked study in patients with symptomatic VMA (i.e. focal VMA leading to symptoms) conducted in US and EU
Symptomatic VMA ocriplasmin 125 μg placebo
245c 81
6 months
Phase II controlled studies
Ocriplasmin total (25-125 µg) Sham injection total
Placebo total
207 25 39 MIVI-II DME
(TG-MV-002) NCT00412451
Phase II multicenter, randomized, sham-injection controlled, double- masked, ascending-dose, dose- range-finding study in patients with diabetic macular edema in EU
Diabetic macular edema
ocriplasmin 25 μg ocriplasmin 75 μg ocriplasmin 125 μg sham injection
51 8 15 15 13
12 months
2
MIVI-III (TG-MV-003) NCT0041295834
Phase II multicenter, randomized, placebo-controlled, double-masked, parallel-group, dose-ranging study in patients undergoing vitrectomy in US
Non-proliferative vitreoretinal disease
ocriplasmin 25 μg ocriplasmin 75 μg ocriplasmin 125 μgc placebo
125 29 33 32 31
6 months
MIVI-IIT (TG-MV-004) NCT0043553935
Phase II multicenter, randomized, sham-injection controlled, double- masked, ascending-dose, dose- range-finding trial in patients with vitreomacular traction in EU
Vitreomacular traction
ocriplasmin 75 μg ocriplasmin 125 μgc,d,e,f,g ocriplasmin 175 μgc,f sham injectiond,g
60g 12 27 11 12
6 months
TG-MV-009 NCT00986362
Phase II single center, randomized placebo-controlled, double-masked study in infants and children scheduled for vitrectomy
Safety and preliminary efficacy as an adjunct to
conventional vitrectomy Ocriplasmin 125 μg placebo
24 16h 8h
6 months
JSEI-TG-AMD-001 NCT00996684
Phase II double-blind, placebo controled safety/efficacy study for treatment of wet AMD in patients who have VMA
Macular degeneration
Ocriplasmin 1.875 mg
9 9
Uncontrolled studies Ocriplasmin
No treatment
111 4 MIVI-I
(TG-MV-001) NCT0012327933
Phase II multicenter, open-label, uncontrolled trial with ascending dose/exposure time in 6 sequential cohorts in patients with vitreomacular traction maculopathy in EU
Vitreomacular traction maculopathy
ocriplasmin 25 μg/1h ocriplasmin 25 μg/24h ocriplasmin 25 μg/7d ocriplasmin 50 μg/24h ocriplasmin 75 μg/24h ocriplasmin 125 μg/24h
60 10 10 10 10 11 9
6 months
TG-MV-008 NCT01055535
Phase II single-center open-label trial in patients with VMT including macular hole
Vitreomacular traction including macular hole
Ocriplasmin 125 µg
17 17
6 months
3
MIVI-10 (TG-MV-010) NCT01159665
Phase II single-center, ascending- exposure time pharmacokinetic trial prior to pars plana vitrectomy
Pharmacokinetics
ocriplasmin 125 µg/5-30min ocriplasmin 125 µg/31-60min ocriplasmin 125 µg/2-4h ocriplasmin 125 µg/24h ocriplasmin 125 µg/7d no ocriplasmin treatment
38 9 9 8 4 4 4
6 weeks
All completed studies Ocriplasmin total (25-175 µg)
Control
783 251
aDuration of post-injection observation period.
bOne patient who was randomized to placebo received ocriplasmin and was included in the safety population.
cThree patients received ocriplasmin in 2 studies and are counted twice, once in both studies in the appropriate dose group. One patient received ocriplasmin 175 μg in the left eye (TG-MV-004) and ocriplasmin 125 μg in the right eye (TG-MV-010). A second patient received ocriplasmin 125 μg in the left eye (TG- MV-003) and ocriplasmin 125 μg in the right eye (TG-MV-006). A third patient received ocriplasmin 125 μg in the right eye (TG-MV-004) and ocriplasmin 125 μg in the left eye (TG-MV-007).
dFifteen patients (ocriplasmin 125 µg: n=12; sham: n=3) were included in a separate cohort that permitted up to 2 open-label injections of ocriplasmin 125 µg if resolution of VMT was not observed by Day 28 post-injection.
eSeven patients who received an ocriplasmin 125 µg injection subsequently each received 2 open-label injections of ocriplasmin 125 µg.
fOne patient randomized to the ocriplasmin 175 μg group received an ocriplasmin injection of approximately 129 μg due to a dilution error. This patient is included in the ocriplasmin 125 μg group.
gTwo patients who received a sham injection each received 2 open-label injections of ocriplasmin 125 µg. Sixty unique patients were enrolled in MIVI-004.
hOne patient had ocriplasmin in one eye and placebo in the other. Another patient had bilateral ocriplasmin treatment.
DME, diabetic macular edema, EU, European Union; MIVI, Microplasmin IntraVitreous Injection; NCT, National Clinical Trial identification number (provided to aid in the location of unpublished studies); TRUST, traction release without surgical treatment; VMA, vitreomacular adhesion.
