An Open Label-study to Compare the Efficacy of Aflibercept Monotherapy for Polypoidal Choroidal Vasculopathy

• Sponsor: Singapore National Eye Centre (Other)
• Overall Status: Completed
• CT.gov ID: NCT03117634
• Collaborator: Bayer (Industry)
• Enrollment: 54
• Location: 1
• Arms: 2
• Actual Duration (Months): 38
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

Polypoidal choroidal neovasculopathy (PCV) is a subtype of wet age related macula degeneration (AMD) occuring more commonly in the Asian population. Besides the phenotypic differences, PCV is thought to have a lesser response to anti VEGF therapy which is the mainstay of treatment for other typical wet AMD. Recent trial data suggest that a combination with photodynamic therapy may help in the visual and anatomical outcome of PCV, and emerging evidence shows favourable outcomes the newer anti VEGF agent, aflibercept 2mg monotherapy. These trials however, have assessed aflibercept in a strict 2mg every 8 weekly regime.

In the clinical setting, a significant an unmet need in the management of PCV is a tailored treatment regime. Here we propose a treatment regimen based on disease activity for PCV with aflibercept mono therapy. A limitation of the 2q8 regime is that it is fixed and does not vary regardless of polyp closure or anatomical outcome at the first time point of assessment (month 3). We hypothesize that after the initial 3 monthly injections of aflibercept, about 50% of PCV will close and become quiescent, and in the remaining 50%, a further 3 monthly injections will increase overall polyp closure rate. After a loadings phase of either 3 or 6 months, all eyes will start on a treat and extend regime (T&E), with a minimum period of 8 weeks and a maximum of 12 weeks between treatments with 2 week increments if PCV remains quiescent. The proposed study aims to evaluate the efficacy of a modified treat and extend regime based on disease activity with aflibercept monotherapy for PCV.

Condition or Disease	Intervention/Treatment	Phase
Age Related Macular Degeneration; Polypoidal Choroidal Vasculopathy	Drug: Treat and Extend with Aflibercept 2mg; Drug: Fixed Dosing with Aflibercept 2mg	Phase 4

Detailed Description

Age related macular degeneration (AMD) is one of the leading causes of blindness worldwide. In its exudative or wet form, choroidal neovascularization (CNV) causes an exudative maculopathy resulting in sudden loss of vision with severe effects on patients' quality of life.1,2 Intra vitreal injections of anti-vascular endothelial growth factor agents (anti-VEGF) agents have become the mainstay of treatment for AMD CNV and have been shown to have favorable outcomes in most AMD CNV subtypes.3,4 In the Asian population however, a particular subtype called polypoidal choroidal vasculopathy (PCV), which affects about 50% of exudative maculopathy, has been shown to have less favorable response to anti-VEGF therapy.5,6 The EVEREST trial, a randomized controlled trial which compares the efficacy of photodynamic therapy (PDT) with or without ranibizumab for treatment of PCV showed that PDT with or without anti VEGF improved polyp closure rate on angiographic assessment but this trial did not take into account vision as a primary end point.7 PDT appears work through its effects on choroidal vasculature, hence making it relevant to PCV which is increasingly thought to be a condition on the pachychoroid spectrum.8 PDT however, as a treatment modality presents several disadvantages. Firstly, PCV often presents as a widely distributed lesion, making it difficult to treat, with a single beam of PDT. Secondly, PDT is limited in its ability to treat lesions in the peripapillary area as there is risk of damage to the optic nerve. Thirdly, features commonly associated with PCV such as a large pigment epithelial detachment (PED) or extensive submacular hemorrhages are not usually suitable for PDT. Fourthly, there is a risk of long-term choroidal atrophy especially if repeated treatments are administered.8,9

There is emerging evidence for the use of aflibercept monotherapy in PCV. Reports range from small case series and retrospective studies to larger prospective studies. Recent data from the PLANET study showed that monotherapy of aflibercept resulted in similar letter gains in visual acuity as compared to combination treatment with PDT at 1 year. Polyp closure rate was also similar between the two groups at 38.9% with monotherapy and 44.8% with combination therapy. The VAULT and APOLLO studies suggest vision and anatomical improvements with 66-72% polyp closure in 1 year.10 These trials however, use a fixed dosing regimen (3 monthly loading doses of 2mg aflibercept followed by fixed dosing every 8 weeks (2q8) totaling 7 injections in 1 year). In addition to resolution of subretinal fluid, recent studies using the novel OCT-angiography (OCT-A) to evaluate choroidal vasculature suggests re-modelling of choroidal vasculature may also be an important therapeutic effect. We reported more prominent reduction in choroidal vessel calibre after combination treatment with PDT and bevacizumab compared to bevacizumab monotherapy. The effect of Aflibercept on choroidal vasculature has been less well studied. Some evidence however, suggested aflibercept may have more profound effect on choroidal vasculature with the reducing choroidal thickness than ranibizumab or bevacizumab.

A significant unmet need in the management of PCV with anti VEGF monotherapy is a practical way of treating patients in the real world setting that maximizes efficacy with minimal number of visits and injections. Clinical trial regimes follow a rigid treatment algorithm that aim to maximize response. In the clinical setting, these regimes are impractical in "real world" patients. Regular intensive course of treatment involves lengthy visits which include consultation time, clinical examination, retinal imaging, and often an intra vitreal injection. In clinical practice this often result in treatment fatigue and in a co-payment healthcare environment in Singapore, may also result in significant financial burden to the patient and society.

While aflibercept affords an 8 weekly treatment regime which is better than other monthly anti VEGF therapy regimes, trial regimes still do not take into account individual patients' disease patterns. This study aims to take disease activity into account to tailor treatment regimes specific for patients. In addition, it aims to provide insight into the outcomes of patients on a more clinically relevant treat and extend (T&E) regime which changes the treatment tempo in relation to disease activity.

Study Design

• Study Type: Interventional
• Actual Enrollment: 54 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Prospective, 2-arm, Non-inferiority, interventional studyProspective, 2-arm, Non-inferiority, interventional study
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label-study to Compare the Efficacy of Aflibercept Monotherapy for Polypoidal Choroidal Vasculopathy Using a Modified Intensive Treat and Extend Regime to a Fixed Dosing Regimen
• Actual Study Start Date: Dec 1, 2017
• Actual Primary Completion Date: Jun 30, 2020
• Actual Study Completion Date: Jan 31, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Fixed dosing group (2Q8) Fixed Dosing with Aflibercept 2mg will be administered at a fixed regime at 8 week intervals through to week 52.	Drug: Fixed Dosing with Aflibercept 2mg; Fixed 8 weekly dosing regime throughout the study duration; Other Names: 2Q8
Experimental: Treat and Extend group (T&E) Reassessment at week 12 (month 3) by repeat examination for disease activity by OCT and indocyanine green angiography (ICGA). Subsequent treatment regime of Treat and Extend with Aflibercept 2mg will depend on disease activity at this point.	Drug: Treat and Extend with Aflibercept 2mg; Drug treatment regime which allows extension of treatment interval based on disease activity; Other Names: T&E

Outcome Measures

Primary Outcome Measures

1. Mean Change in Best Corrected Visual Acuity (BCVA) [From Baseline to Week 52]

   Mean Change in Best corrected visual acuity (BCVA) from baseline to week 52 for personalized and fixed regimen. it is a Non-inferiority of personalized to fixed regimen for mean change in BCVA from baseline to week 52 (Non-inferiority is considered as -5 ETDRS Letters difference )

Secondary Outcome Measures

1. Mean Change in Central Sub Field Thickness [From Baseline to Week 52]

   central sub field thickness (CSFT) was defined as the average thickness of the macula in the central 1 mm ETDRS grid. Defined as the thickness from the inner retinal boundary at the location of the inner limiting membrane (ILM) to the outer retinal boundary at Bruch's membrane (BM). Change in the central sub field thickness (CSFT) after the treatment was assessed , the measurement was done by optical coherence tomography (OCT). the measures were taken at baseline and week 52, the change between the two measurements ( baseline to week 52) were assessed in both groups to understand the effect of treatment on CSFT

2. Number of Participants With Complete Polypoidal Lesion Closure [At Week 52]

   This measure reports the Number of participants with complete polypoidal lesion closure defined as those showing no late leakage on Indocyanine green angiography (ICGA).

3. Number of Injections [From Baseline to Week 52]

   number of aflibercept injections administered in personalised and fixed groups

Eligibility Criteria

Criteria

• Ages Eligible for Study: 45 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria Participant

1. Male or female study participants, age >=45 years of age at the time of informed consent.

2. Best corrected ETDRS visual acuity score <= 78 (ie 20/32 or worse)

3. Diagnosis of PCV based on ICGA

4. Presence of intra retinal or subretinal fluid/blood at the fovea as seen on OCT

5. Treatment naïve

6. Media clarity, pupillary dilation and individual cooperation sufficient for study procedure including fundus photography.

7. Able and willing to provide informed consent.

1.2. Exclusion Criteria Participant

1. Medical condition that, in the opinion of the investigator, would preclude participation in the study (e.g.unstable medical status including blood pressure, cardiovascular disease, and glycemic control).

2. Participation in an investigational trial within 30 days of enrolment which involves treatment with unapproved investigational drug

3. Known allergy to any component of the study drug.

4. Blood pressure > 180/110 (systolic above 180 OR diastolic above 110 on repeated measurements). If blood pressure is brought below 180/110 by anti-hypertensive treatment, individual can become eligible.

5. Myocardial infarction, other acute cardiac event requiring hospitalization, stroke, transient ischemic attack, or treatment for acute congestive heart failure within 4 months prior to randomization.

6. Systemic anti-VEGF or pro-VEGF treatment within four months prior to randomization or anticipated use during the study.

Study Eye

1. Eye with intra retinal or subretinal fluid due to other causes than PCV

2. An ocular condition is present (other than PCV) that, in the opinion of the investigator, might affect intra or sub retinal fluid or alter visual acuity during the course of the study (e.g., diabetic macula edema (DME), vein occlusion, uveitis or other ocular inflammatory disease, neovascular glaucoma, etc.)

3. Substantial cataract that, in the opinion of the investigator, is likely to be decreasing visual acuity by more than three lines (i.e., cataract would be reducing acuity to worse than 20/40 if eye was otherwise normal).

4. Any intraocular surgery within 3 months of enrollment

5. Treatment with intra vitreal corticosteroids

6. History of retinal detachment or surgery for retinal detachment

7. History of vitrectomy

8. History of macular hole

9. Evidence of vitreomacular traction that may preclude resolution of macular edema > 4 disc areas of intra/sub retinal hemorrhage

10. Aphakia

11. Exam evidence of external ocular infection, including conjunctivitis, chalazion, or significant blepharitis

Other Eye

1. Active intraocular inflammation

2. History of uveitis

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Singapore National Eye Centre	Singapore	Singpore	Singapore	168751

Sponsors and Collaborators

• Singapore National Eye Centre
• Bayer

Investigators

• Principal Investigator: Gemmy Cheung, SNEC

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 26, 2019

More Information

Publications

None provided.

• Responsible Party: Singapore National Eye Centre
• ClinicalTrials.gov Identifier: NCT03117634
• Other Study ID Numbers: R1448/31/2017
• First Posted: Apr 18, 2017
• Last Update Posted: Aug 18, 2021
• Last Verified: Aug 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Singapore National Eye Centre: anti vegf; aflibercept; treat and extend
• Additional relevant MeSH terms: Macular Degeneration; Vascular Diseases; Aflibercept

Study Results

Participant Flow

Arm/Group Title	Personalised Group	Fixed Group
Arm/Group Description	The participants received an induction phase of treatment defined as 4 weekly intravitreal aflibercept 2mg/0.05ml at week 0, week 4 and week 8. At week 12, the participants had repeat ICGA and OCT. At week 12, participants in this group, in whom, polypoidal lesions had completely regressed on ICGA would enter into the treat and extend (TNE)phase. Participants with presence of polypoidal lesions (PL) on ICGA (with or without fluid on OCT) would continue three 4-weekly injections till week 24, and enter TNE phase from week 24 onwards.	The participants received an induction phase of treatment defined as 4 weekly intravitreal aflibercept 2mg/0.05ml at week 0, week 4 and week 8. At week 12, all participants had repeat ICGA and OCT. Participants in the fixed group went on to receive fix doses of 8-weekly aflibercept 2mn/0.05ml after the induction phase for the remaining duration of the study.
Period Title: Overall Study
STARTED	41	13
COMPLETED	39	13
NOT COMPLETED	2	0

Baseline Characteristics

Arm/Group Title	Personalised Group	Fixed Group	Total
Arm/Group Description	The participants received an induction phase of treatment defined as 4 weekly intravitreal aflibercept 2mg/0.05ml at week 0, week 4 and week 8. At week 12, the participants had repeat ICGA and OCT. At week 12, participants in this group, in whom, polypoidal lesions had completely regressed on ICGA would enter into the treat and extend (TNE)phase. Participants with presence of polypoidal lesions (PL) on ICGA (with or without fluid on OCT) would continue three 4-weekly injections till week 24, and enter TNE phase from week 24 onwards.	All Study participants received an induction phase of treatment defined as 4 weekly intravitreal aflibercept 2mg/0.05ml at week 0, week 4 and week 8. At week 12, all participants had repeat ICGA and OCT. Participants in the fixed group went on to receive fix doses of 8-weekly aflibercept 2mn/0.05ml after the induction phase for the remaining duration of the study.	Total of all reporting groups
Overall Participants	39	13	52
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	69.2 (9.3)	69.3 (6.6)	69.25 (8.6)
Sex: Female, Male (Count of Participants)
Female	14 35.9%	5 38.5%	19 36.5%
Male	25 64.1%	8 61.5%	33 63.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	39 100%	13 100%	52 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Singapore	39 100%	13 100%	52 100%
Best Corrected Visual Acuity(BCVA) (ETDRS Letters (units on a scale)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ETDRS Letters (units on a scale)]	58 (14.2)	62.8 (12.6)	60.4 (14.3)
Central sub field thickness (CSFT) (microns) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [microns]	446.5 (181.6)	483.2 (189.3)	464.85 (183.5)

Outcome Measures

1. Primary Outcome

Title	Mean Change in Best Corrected Visual Acuity (BCVA)
Description	Mean Change in Best corrected visual acuity (BCVA) from baseline to week 52 for personalized and fixed regimen. it is a Non-inferiority of personalized to fixed regimen for mean change in BCVA from baseline to week 52 (Non-inferiority is considered as -5 ETDRS Letters difference )
Time Frame	From Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Mean Change in Best corrected visual acuity (BCVA) from baseline to week 52 for personalized and fixed regimen. it is a Non-inferiority of personalized to fixed regimen for mean change in BCVA from baseline to week 52

Arm/Group Title	Personalised Group	Fixed Group
Arm/Group Description	The participants received an induction phase of treatment defined as 4 weekly intravitreal aflibercept 2mg/0.05ml at week 0, week 4 and week 8. At week 12, the participants had repeat ICGA and OCT. At week 12, participants in this group, in whom, polypoidal lesions had completely regressed on ICGA would enter into the treat and extend (TNE)phase. Participants with presence of polypoidal lesions (PL) on ICGA (with or without fluid on OCT) would continue three 4-weekly injections till week 24, and enter TNE phase from week 24 onwards.	The participants received an induction phase of treatment defined as 4 weekly intravitreal aflibercept 2mg/0.05ml at week 0, week 4 and week 8. At week 12, all participants had repeat ICGA and OCT. Participants in the fixed group went on to receive fix doses of 8-weekly aflibercept 2mn/0.05ml after the induction phase for the remaining duration of the study.
Measure Participants	39	13
Measure Eyes	39	13
Mean (95% Confidence Interval) [ETDRS Letters]	8.1	7.9

2. Secondary Outcome

Title	Mean Change in Central Sub Field Thickness
Description	central sub field thickness (CSFT) was defined as the average thickness of the macula in the central 1 mm ETDRS grid. Defined as the thickness from the inner retinal boundary at the location of the inner limiting membrane (ILM) to the outer retinal boundary at Bruch's membrane (BM). Change in the central sub field thickness (CSFT) after the treatment was assessed , the measurement was done by optical coherence tomography (OCT). the measures were taken at baseline and week 52, the change between the two measurements ( baseline to week 52) were assessed in both groups to understand the effect of treatment on CSFT
Time Frame	From Baseline to Week 52

Outcome Measure Data

Analysis Population Description

change in the central sub field thickness (CSFT) assessed by OCT from baseline to week 52 between personalised and fixed group

Arm/Group Title	Personalised Group	Fixed Group
Arm/Group Description	The participants received an induction phase of treatment defined as 4 weekly intravitreal aflibercept 2mg/0.05ml at week 0, week 4 and week 8. At week 12, the participants had repeat ICGA and OCT. At week 12, participants in this group, in whom, polypoidal lesions had completely regressed on ICGA would enter into the treat and extend (TNE)phase. Participants with presence of polypoidal lesions (PL) on ICGA (with or without fluid on OCT) would continue three 4-weekly injections till week 24, and enter TNE phase from week 24 onwards.	The participants received an induction phase of treatment defined as 4 weekly intravitreal aflibercept 2mg/0.05ml at week 0, week 4 and week 8. At week 12, all participants had repeat ICGA and OCT. Participants in the fixed group went on to receive fix doses of 8-weekly aflibercept 2mn/0.05ml after the induction phase for the remaining duration of the study.
Measure Participants	39	13
Mean (Standard Deviation) [um]	-248.8 (169.9)	-164.8 (148.9)

3. Secondary Outcome

Title	Number of Participants With Complete Polypoidal Lesion Closure
Description	This measure reports the Number of participants with complete polypoidal lesion closure defined as those showing no late leakage on Indocyanine green angiography (ICGA).
Time Frame	At Week 52

Outcome Measure Data

Analysis Population Description

number of participants with complete polypoidal lesion closure as detected on Indocyanine green angiography (ICGA) as no leakage on late ICGA stage between personalised and fixed groups

Arm/Group Title	Personalised Group	Fixed Group
Arm/Group Description	The participants received an induction phase of treatment defined as 4 weekly intravitreal aflibercept 2mg/0.05ml at week 0, week 4 and week 8. At week 12, the participants had repeat ICGA and OCT. At week 12, participants in this group, in whom, polypoidal lesions had completely regressed on ICGA would enter into the treat and extend (TNE)phase. Participants with presence of polypoidal lesions (PL) on ICGA (with or without fluid on OCT) would continue three 4-weekly injections till week 24, and enter TNE phase from week 24 onwards.	The participants received an induction phase of treatment defined as 4 weekly intravitreal aflibercept 2mg/0.05ml at week 0, week 4 and week 8. At week 12, all participants had repeat ICGA and OCT. Participants in the fixed group went on to receive fix doses of 8-weekly aflibercept 2mn/0.05ml after the induction phase for the remaining duration of the study.
Measure Participants	39	13
Count of Participants [Participants]	21 53.8%	5 38.5%

4. Secondary Outcome

Title	Number of Injections
Description	number of aflibercept injections administered in personalised and fixed groups
Time Frame	From Baseline to Week 52

Outcome Measure Data

Analysis Population Description

number of aflibercept injections administered in the induction phase in both groups

Arm/Group Title	Personalised Group	Fixed Group
Arm/Group Description	The participants received an induction phase of treatment defined as 4 weekly intravitreal aflibercept 2mg/0.05ml at week 0, week 4 and week 8. At week 12, the participants had repeat ICGA and OCT. At week 12, participants in this group, in whom, polypoidal lesions had completely regressed on ICGA would enter into the treat and extend (TNE)phase. Participants with presence of polypoidal lesions (PL) on ICGA (with or without fluid on OCT) would continue three 4-weekly injections till week 24, and enter TNE phase from week 24 onwards.	The participants received an induction phase of treatment defined as 4 weekly intravitreal aflibercept 2mg/0.05ml at week 0, week 4 and week 8. At week 12, all participants had repeat ICGA and OCT. Participants in the fixed group went on to receive fix doses of 8-weekly aflibercept 2mn/0.05ml after the induction phase for the remaining duration of the study.
Measure Participants	40	13
Mean (Standard Deviation) [Injections]	8.2 (0.9)	8 (0)

Adverse Events

Time Frame	The Adverse events (AE) and serious Adverse events (SAE) were recorded on or after the date of the administration of first study treatment, for an average of 1 year.
Adverse Event Reporting Description	Adverse events : Any Hospitalisation for routine treatment or monitoring of the studied indication not associated with any deterioration in condition, hospitalisation for elective or preplanned treatment for a pre-existing condition that is unrelated to the indication under study and has not worsened since the start of the study and treatment on an emergency outpatient basis for an event not fulfilling the definitions of a SAE given above and not resulting in hospital admission.
Arm/Group Title	Personalised Group		Fixed Group
Arm/Group Description	The participants received an induction phase of treatment defined as 4 weekly intravitreal aflibercept 2mg/0.05ml at week 0, week 4 and week 8. At week 12, the participants had repeat ICGA and OCT. At week 12, participants in this group, in whom, polypoidal lesions had completely regressed on ICGA would enter into the treat and extend (TNE)phase. Participants with presence of polypoidal lesions (PL) on ICGA (with or without fluid on OCT) would continue three 4-weekly injections till week 24, and enter TNE phase from week 24 onwards.		The participants received an induction phase of treatment defined as 4 weekly intravitreal aflibercept 2mg/0.05ml at week 0, week 4 and week 8. At week 12, all participants had repeat ICGA and OCT. Participants in the fixed group went on to receive fix doses of 8-weekly aflibercept 2mn/0.05ml after the induction phase for the remaining duration of the study.
All Cause Mortality
	Personalised Group		Fixed Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/39 (0%)		0/13 (0%)
Serious Adverse Events
	Personalised Group		Fixed Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/39 (7.7%)		0/13 (0%)
Gastrointestinal disorders
Cancer	1/39 (2.6%)		0/13 (0%)
Ulcer	1/39 (2.6%)		0/13 (0%)
Social circumstances
Fall	1/39 (2.6%)		0/13 (0%)
Other (Not Including Serious) Adverse Events
	Personalised Group		Fixed Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/39 (25.6%)		4/13 (30.8%)
Eye disorders
Drop in Visual Acuity	2/39 (5.1%)		1/13 (7.7%)
Stye (Extra-Ocular)	1/39 (2.6%)		0/13 (0%)
Punctate epithelial erosion	1/39 (2.6%)		1/13 (7.7%)
Peri-orbital Oedema (Extra-Ocular)	1/39 (2.6%)		0/13 (0%)
Drop in vision due to cataract	2/39 (5.1%)		0/13 (0%)
riased intraocular pressure	1/39 (2.6%)		1/13 (7.7%)
Rapid Active Disease Progression	1/39 (2.6%)		0/13 (0%)
General disorders
Raised blood pressure	1/39 (2.6%)		1/13 (7.7%)

Limitations/Caveats

More participants in the personalised group(3:1)increased the power to detect outcomes. 52 week study duration may not fully demonstrate the advantages of a TNE regimen,PL closure. Study not powered to detect the difference in PL closure at month 3.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Contract Partners shall provide to Sponsor any proposed publication or oral presentation relating to the Study or Study Drug and Results (Publications), at least thirty days prior to the intended submission or presentation in order to allow SPONSOR to review it. If Sponsor does not notify Contract Partner within thirty (30) days of receipt of intended Publication, Contract Partner shall be free to publish.