INTREPID - IRay Plus Anti-VEGF Treatment For Patients With Wet AMD

• Sponsor: Oraya Therapeutics, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01016873
• Collaborator: (none)
• Enrollment: 230
• Locations: 21
• Arms: 4
• Duration (Months): 53
• Patients Per Site: 11
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to confirm the safety and establish the effectiveness of two doses from the IRay System for the treatment of wet AMD.

Condition or Disease	Intervention/Treatment	Phase
AMD; Wet AMD; Age-Related Macular Degeneration; Wet Age-Related Macular Degeneration; Macular Degeneration; Eye Diseases; Retinal Diseases	Device: IRay	Phase 2

Detailed Description

The purpose of this study is to confirm the safety of low voltage external beam radiotherapy using the IRay System at two dose levels for the treatment of CNV secondary to neovascular AMD and to determine if the IRay System is effective in sparing the number of Lucentis injections during the first 12 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 230 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Double-masked, Sham Controlled, Dose-ranging Study to Evaluate the Safety and Effectiveness of Low Voltage Stereotactic Radiosurgery in Patients With Choroidal Neovascularization (CNV) Secondary to Age-related Macular Degeneration (AMD)
• Study Start Date: Nov 1, 2009
• Actual Primary Completion Date: May 1, 2012
• Actual Study Completion Date: Apr 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 16 Gy IRay 16 Gy IRay + PRN Lucentis®	Device: IRay; Low voltage stereotactic radiotherapy system
Sham Comparator: Sham 16 Gy IRay Sham 16 Gy IRay + PRN Lucentis®	Device: IRay; Low voltage stereotactic radiotherapy system
Experimental: 24 Gy IRay 24 Gy IRay + PRN Lucentis®	Device: IRay; Low voltage stereotactic radiotherapy system
Sham Comparator: Sham 24 Gy IRay Sham 24 Gy IRay + PRN Lucentis®	Device: IRay; Low voltage stereotactic radiotherapy system

Outcome Measures

Primary Outcome Measures

1. Number of Lucentis® Injections Up To And Including Week 52 [During the first 52 weeks.]

Secondary Outcome Measures

1. Change in Mean Visual Acuity (VA) [Weeks 12, 28, 52 and 104.]

2. Percentage (Pct.) of Patients (Pts.) Losing < 15 Letters of Best Correct Visual Acuity (BCVA) From Baseline (Base.) [Weeks 12, 28 and 52.]

3. Percentage (Pct.) of Patients (Pts.) Gaining ≥ 15 Letters of Best Correct Visual Acuity (BCVA) From Baseline (Base.) [Weeks 12, 28 and 52.]

4. Percentage (Pct.) of Patients (Pts.) Gaining ≥ 0 Letters of Best Correct Visual Acuity (BCVA) From Baseline (Base.) [Weeks 12, 28 and 52.]

5. Time From Mandatory Injection at Day 0 to the First PRN Injection. [52 Weeks]

6. Total Number (No.) of Lucentis® Injections (Inject.) During The First 12, 28, and 104 Weeks. [Week 12, 28, and 104]

7. Mean Change in Choroidal Neovascularization (CNV) as % of Lesion on Fluorescein Angiography (FA) From Baseline to Week 52 [Week 52]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must have neovascular AMD diagnosed within the previous 3 years, have received at least 3 injections with Lucentis® or Avastin® within the previous year and have the need for treatment with anti-VEGF therapy due to increased fluid or persistent cysts on OCT, or leakage on FA.

• Patients must have a total lesion size of <12 disc areas and a CNV lesion with the greatest linear dimension of <6 mm, but not greater than 3 mm from the center of the fovea to the furthest point on the lesion perimeter.

• The distance from the center of the fovea to the nearest edge of the optic disc should be not less than 3 mm.

• Patients must Patient must be at least 50 years of age.

• Women must be post-menopausal ≥1 year or surgically sterilized, or a pregnancy screen must be performed prior to the study and a reliable form of contraception approved by the investigator must be maintained during the study.

• Patient must have best corrected visual acuity of 75 to 25 letters in the study eye and at least 20 letters in the fellow eye.

Exclusion Criteria:

• CNV due to causes other than AMD, including ocular histoplasmosis syndrome, angioid streaks, multifocal choroiditis, choroidal rupture, or pathologic myopia (spherical equivalent ≥ -8 diopters).

• An axial length of ≤20 mm or ≥26 mm.

• Previously diagnosed with Diabetes Mellitus and/or an HbA1c of >6.5%, and with retinal findings consistent with diabetic retinopathy.

• Prior or concurrent therapies for age related macular degeneration including submacular surgery, subfoveal thermal laser photocoagulation (with or without photographic evidence), transpupillary thermotherapy (TTT), ocular photodynamic therapy, radiation therapy to the head or neck in the study eye.

• Previous posterior vitrectomy, or any surgery in the study eye within 6 months or YAG capsulotomy within 3 months prior to the screening visit.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	LKH Graz	Graz		Austria	A-8036
2	Universitätsklinik Innsbruck	Innsbruck		Austria	A-6020
3	Hanusch Krankenhaus Wien	Wien		Austria	A-1140
4	Ordination Prof. Michael Stur	Wien		Austria	A-1180
5	Fakultni Nemocnice Brno	Brno		Czech Republic	625 00
6	Fakultni nemocnice Hradec Kralove	Hradec Kralove		Czech Republic	500 05
7	Fakultni Nemocnice Olomouc	Olomouc		Czech Republic	775 20
8	Faculty Hospital Kralovske Vinohrady	Prague		Czech Republic	100 34
9	General Faculty Hospital Prague	Prague		Czech Republic	128 08
10	Military Hospital Prague	Prague		Czech Republic	169 02
11	Kopfklinikum University Hospital Heidelberg	Heidelberg	Baden-Württemberg	Germany	69120
12	University Eye Hospital	Tübingen	Baden-Württemberg	Germany	72076
13	Klinik für Augenheilkunde	Neubrandenburg	Mecklenburg-Vorpommern	Germany	17036
14	Università Vita-Salute Istituto Scientifico San Raffaele	Milano		Italy	I-20132
15	Royal Victoria Hospital	Belfast		United Kingdom	BT12 6BA
16	Bradford Royal Infirmary	Bradford		United Kingdom	BDP 6RJ
17	Torbay Hospital	Devon		United Kingdom	TQ2 7AA
18	King's College	London		United Kingdom	SE5 9RS
19	Manchester Royal Eye Hospital	Manchester		United Kingdom	M13 9WL
20	Southampton General Hospital	Southampton		United Kingdom	SO16 6YD
21	Royal Wolverhampton Hospital NHS Foundation Trust	Wolverhampton		United Kingdom	WV3 9QR

Sponsors and Collaborators

• Oraya Therapeutics, Inc.

Investigators

• Study Director: Denis O'Shaughnessy, Ph.D., Oraya Therapeutics, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Oraya Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT01016873
• Other Study ID Numbers: CLH002
• First Posted: Nov 20, 2009
• Last Update Posted: Dec 5, 2014
• Last Verified: Dec 1, 2014

• Keywords provided by Oraya Therapeutics, Inc.: Oraya; Oraya Therapeutics, Inc.; low voltage stereotactic radiotherapy; radiotherapy; IRay; Ranibizumab; Lucentis; AMD; Macular Degeneration; xray; radiation; x ray; external beam radiation; radiosurgery
• Additional relevant MeSH terms: Macular Degeneration; Eye Diseases; Retinal Diseases

Study Results

Participant Flow

Arm/Group Title	16 Gy IRay	24 Gy IRay	Sham IRay
Arm/Group Description	16 Gy IRay + PRN Lucentis® IRay: Low voltage stereotactic radiotherapy system	24 Gy IRay + PRN Lucentis® IRay: Low voltage stereotactic radiotherapy system	Sham 24 or 16 Gy IRay + PRN Lucentis® IRay: Low voltage stereotactic radiotherapy system
Period Title: 12 Months
STARTED	75	75	80
COMPLETED	74	72	79
NOT COMPLETED	1	3	1
Period Title: 12 Months
STARTED	74	72	79
COMPLETED	69	68	73
NOT COMPLETED	5	4	6
Period Title: 12 Months
STARTED	69	68	73
COMPLETED	58	64	67
NOT COMPLETED	11	4	6

Baseline Characteristics

Arm/Group Title	16 Gy IRay	24 Gy IRay	Sham IRay	Total
Arm/Group Description	16 Gy IRay + PRN Lucentis® IRay: Low voltage stereotactic radiotherapy system	24 Gy IRay + PRN Lucentis® IRay: Low voltage stereotactic radiotherapy system	Sham 16 or 24 Gy IRay + PRN Lucentis® IRay: Low voltage stereotactic radiotherapy system	Total of all reporting groups
Overall Participants	75	75	80	230
Age, Customized (years) [Mean (Standard Deviation) ]
Age	73.35 (7.18)	73.77 (8.26)	73.45 (7.14)	73.52 (7.51)
Sex: Female, Male (Count of Participants)
Female	43 57.3%	48 64%	49 61.3%	140 60.9%
Male	32 42.7%	27 36%	31 38.8%	90 39.1%
Region of Enrollment (participants) [Number]
Czech Republic	48 64%	29 38.7%	47 58.8%	124 53.9%
Austria	4 5.3%	20 26.7%	4 5%	28 12.2%
Germany	6 8%	7 9.3%	10 12.5%	23 10%
United Kingdom	14 18.7%	18 24%	17 21.3%	49 21.3%
Italy	3 4%	1 1.3%	2 2.5%	6 2.6%

Outcome Measures

1. Primary Outcome

Title	Number of Lucentis® Injections Up To And Including Week 52
Time Frame	During the first 52 weeks.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	16 Gy IRay	24 Gy IRay	Sham IRay
Arm/Group Description	16 Gy IRay + PRN Lucentis® IRay: Low voltage stereotactic radiotherapy system	24 Gy IRay + PRN Lucentis® IRay: Low voltage stereotactic radiotherapy system	Sham 16 or 24 Gy IRay + PRN Lucentis® IRay: Low voltage stereotactic radiotherapy system
Measure Participants	75	75	80
Mean (Standard Deviation) [Injections]	2.64 (2.46)	2.44 (2.41)	3.73 (2.58)

2. Secondary Outcome

Title	Change in Mean Visual Acuity (VA)
Time Frame	Weeks 12, 28, 52 and 104.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	16 Gy IRay	24 Gy IRay	Sham IRay
Arm/Group Description	16 Gy IRay + PRN Lucentis® IRay: Low voltage stereotactic radiotherapy system	24 Gy IRay + PRN Lucentis® IRay: Low voltage stereotactic radiotherapy system	Sham 16 or 24 Gy IRay + PRN Lucentis® IRay: Low voltage stereotactic radiotherapy system
Measure Participants	75	75	80
Visual Acuity (VA) - Baseline	57.91 (12.72)	58.75 (12.79)	59.29 (13.09)
Mean change in VA Week 12, n = 73, 71, 78	0.86 (5.68)	1.85 (9.73)	2.06 (6.79)
Mean change in VA Week 28, n = 73, 73, 77	-0.33 (8.25)	2.04 (8.58)	1.42 (7.91)
Mean change in VA Week 52, n = 74, 72, 79	-0.28 (8.77)	0.40 (10.33)	-0.58 (10.56)
Mean change in VA Week 104, n = 68, 68, 73	-10.03 (16.45)	-7.49 (16.49)	-6.71 (17.08)

3. Secondary Outcome

Title	Percentage (Pct.) of Patients (Pts.) Losing < 15 Letters of Best Correct Visual Acuity (BCVA) From Baseline (Base.)
Time Frame	Weeks 12, 28 and 52.

Outcome Measure Data

Analysis Population Description

Number of Participants Analyzed: Week 12: n = 73, 71, 78 Week 28: n = 73, 73, 77 Week 52: n = 74, 72, 79

Arm/Group Title	16 Gy IRay	24 Gy IRay	Sham IRay
Arm/Group Description	16 Gy IRay + PRN Lucentis® IRay: Low voltage stereotactic radiotherapy system	24 Gy IRay + PRN Lucentis® IRay: Low voltage stereotactic radiotherapy system	Sham 16 or 24 Gy IRay + PRN Lucentis® IRay: Low voltage stereotactic radiotherapy system
Measure Participants	75	75	80
Pct. of Pts. Losing <15 Letters From Base. - W12	100	97	97
Pct. of Pts. Losing <15 Letters From Base. - W28	97	96	97
Pct. of Pts. Losing <15 Letters From Base. - W52	93	89	92

4. Secondary Outcome

Title	Percentage (Pct.) of Patients (Pts.) Gaining ≥ 15 Letters of Best Correct Visual Acuity (BCVA) From Baseline (Base.)
Time Frame	Weeks 12, 28 and 52.

Outcome Measure Data

Analysis Population Description

Number of Participants Analyzed: Week 12: n = 73, 71, 78 Week 28: n = 73, 73, 77 Week 52: n = 74, 72, 79

Arm/Group Title	16 Gy IRay	24 Gy IRay	Sham IRay
Arm/Group Description	16 Gy IRay + PRN Lucentis® IRay: Low voltage stereotactic radiotherapy system	24 Gy IRay + PRN Lucentis® IRay: Low voltage stereotactic radiotherapy system	Sham 16 or 24 Gy IRay + PRN Lucentis® IRay: Low voltage stereotactic radiotherapy system
Measure Participants	75	75	80
Pct. of Pts. Gaining >=15 Letters from Base. -W12	0	6	1
Pct. of Pts. Gaining >=15 Letters from Base. -W28	4	4	3
Pct. of Pts. Gaining >=15 Letters from Base. -W52	4	4	5

5. Secondary Outcome

Title	Percentage (Pct.) of Patients (Pts.) Gaining ≥ 0 Letters of Best Correct Visual Acuity (BCVA) From Baseline (Base.)
Time Frame	Weeks 12, 28 and 52.

Outcome Measure Data

Analysis Population Description

Number of Participants Analyzed: Week 12: n = 73, 71, 78 Week 28: n = 73, 73, 77 Week 52: n = 74, 72, 79

Arm/Group Title	16 Gy IRay	24 Gy IRay	Sham IRay
Arm/Group Description	16 Gy IRay + PRN Lucentis® IRay: Low voltage stereotactic radiotherapy system	24 Gy IRay + PRN Lucentis® IRay: Low voltage stereotactic radiotherapy system	Sham 16 or 24 Gy IRay + PRN Lucentis® IRay: Low voltage stereotactic radiotherapy system
Measure Participants	75	75	80
Pct. of Pts. Gaining >=0 Letters From Base. - W12	60	65	74
Pct. of Pts. Gaining >=0 Letters From Base. - W28	52	62	64
Pct. of Pts. Gaining >=0 Letters From Base. - W52	53	57	57

6. Secondary Outcome

Title	Time From Mandatory Injection at Day 0 to the First PRN Injection.
Time Frame	52 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	16 Gy IRay	24 Gy IRay	Sham IRay
Arm/Group Description	16 Gy IRay + PRN Lucentis® IRay: Low voltage stereotactic radiotherapy system	24 Gy IRay + PRN Lucentis® IRay: Low voltage stereotactic radiotherapy system	Sham 16 or 24 Gy IRay + PRN Lucentis® IRay: Low voltage stereotactic radiotherapy system
Measure Participants	75	75	80
Median (95% Confidence Interval) [Weeks]	16.29	16.71	13.14

7. Secondary Outcome

Title	Total Number (No.) of Lucentis® Injections (Inject.) During The First 12, 28, and 104 Weeks.
Time Frame	Week 12, 28, and 104

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	16 Gy IRay	24 Gy IRay	Sham IRay
Arm/Group Description	16 Gy IRay + PRN Lucentis® IRay: Low voltage stereotactic radiotherapy system	24 Gy IRay + PRN Lucentis® IRay: Low voltage stereotactic radiotherapy system	Sham 16 or 24 Gy IRay + PRN Lucentis® IRay: Low voltage stereotactic radiotherapy system
Measure Participants	75	75	80
Mean No. of Injections - Week 12, n = 75,75,80	0.57 (0.70)	0.56 (0.74)	0.73 (0.78)
No. of Injections - Week 28, n = 75,75,80	1.51 (1.35)	1.28 (1.37)	1.83 (1.41)
Mean No. of Injections - Week 104, n=75,75,80	4.48 (3.94)	5.37 (4.57)	6.61 (4.28)

8. Secondary Outcome

Title	Mean Change in Choroidal Neovascularization (CNV) as % of Lesion on Fluorescein Angiography (FA) From Baseline to Week 52
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	16 Gy IRay	24 Gy IRay	Sham IRay
Arm/Group Description	16 Gy IRay + PRN Lucentis® IRay: Low voltage stereotactic radiotherapy system	24 Gy IRay + PRN Lucentis® IRay: Low voltage stereotactic radiotherapy system	Sham 16 or 24 Gy IRay + PRN Lucentis® IRay: Low voltage stereotactic radiotherapy system
Measure Participants	29	28	44
Mean (Standard Deviation) [CNV as % of Lesion]	-0.16 (0.33)	-0.18 (0.33)	-0.10 (0.26)

Adverse Events

Time Frame	Adverse event reporting from Baseline through week 104.
Arm/Group Title	16 Gy IRay		24 Gy IRay		Sham IRay
Arm/Group Description	16 Gy IRay + PRN Lucentis® IRay: Low voltage stereotactic radiotherapy system		24 Gy IRay + PRN Lucentis® IRay: Low voltage stereotactic radiotherapy system		Sham 16 or 24 Gy IRay + PRN Lucentis® IRay: Low voltage stereotactic radiotherapy system
All Cause Mortality
	16 Gy IRay		24 Gy IRay		Sham IRay
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	16 Gy IRay		24 Gy IRay		Sham IRay
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/75 (16%)		8/75 (10.7%)		7/80 (8.8%)
Blood and lymphatic system disorders
Microcytic anaemia	1/75 (1.3%)	1	0/75 (0%)	0	0/80 (0%)	0
Eye disorders
Choroidal neovascularisation	0/75 (0%)	0	0/75 (0%)	0	1/80 (1.3%)	1
Retinal Vein Occlusion	0/75 (0%)	0	0/75 (0%)	0	1/80 (1.3%)	1
Gastrointestinal disorders
Gastrointestinal disorder	1/75 (1.3%)	1	0/75 (0%)	0	0/80 (0%)	0
Rectal Haemorrhage	1/75 (1.3%)	1	0/75 (0%)	0	0/80 (0%)	0
Intestinal obstruction	0/75 (0%)	0	0/75 (0%)	0	1/80 (1.3%)	1
General disorders
Impaired healing	0/75 (0%)	0	0/75 (0%)	0	1/80 (1.3%)	1
Infections and infestations
Pneumonia	1/75 (1.3%)	1	2/75 (2.7%)	2	1/80 (1.3%)	1
Injury, poisoning and procedural complications
Femur fracture	1/75 (1.3%)	1	0/75 (0%)	0	0/80 (0%)	0
Hip fracture	0/75 (0%)	0	0/75 (0%)	0	1/80 (1.3%)	1
Post procedural complication	0/75 (0%)	0	0/75 (0%)	0	1/80 (1.3%)	1
Upper limb fracture	0/75 (0%)	0	0/75 (0%)	0	1/80 (1.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colorectal cancer	0/75 (0%)	0	1/75 (1.3%)	1	1/80 (1.3%)	1
Nervous system disorders
Convulsion	0/75 (0%)	0	0/75 (0%)	0	1/80 (1.3%)	1
Intracranial haematoma	0/75 (0%)	0	0/75 (0%)	0	1/80 (1.3%)	1
Sciatica	1/75 (1.3%)	1	0/75 (0%)	0	0/80 (0%)	0
Stroke	0/75 (0%)	0	1/75 (1.3%)	1	0/80 (0%)	0
Renal and urinary disorders
Urinary bladder polyp	1/75 (1.3%)	1	0/75 (0%)	0	0/80 (0%)	0
Reproductive system and breast disorders
Colpocele	1/75 (1.3%)	1	0/75 (0%)	0	0/80 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	2/75 (2.7%)	2	0/75 (0%)	0	0/80 (0%)	0
Pulmonary hypertension	1/75 (1.3%)	1	0/75 (0%)	0	0/80 (0%)	0
Surgical and medical procedures
Limb operation	0/75 (0%)	0	2/75 (2.7%)	2	0/80 (0%)	0
Cyst drainage	0/75 (0%)	0	1/75 (1.3%)	1	0/80 (0%)	0
Foot operation	0/75 (0%)	0	1/75 (1.3%)	1	0/80 (0%)	0
Vascular disorders
Hypertension	1/75 (1.3%)	1	0/75 (0%)	0	0/80 (0%)	0
Other (Not Including Serious) Adverse Events
	16 Gy IRay		24 Gy IRay		Sham IRay
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/75 (26.7%)		23/75 (30.7%)		24/80 (30%)
Eye disorders
Worsening of macular degeneration	7/75 (9.3%)	7	6/75 (8%)	6	8/80 (10%)	8
Retinal haemorrhage	4/75 (5.3%)	4	2/75 (2.7%)	2	6/80 (7.5%)	6
Visual acuity reduced	5/75 (6.7%)	5	3/75 (4%)	3	4/80 (5%)	4
Blepharitis	2/75 (2.7%)	2	7/75 (9.3%)	7	2/80 (2.5%)	2
Infections and infestations
Nasopharyngitis	2/75 (2.7%)	2	7/75 (9.3%)	7	4/80 (5%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Institution and the Principal Investigator agree not to publish or issue a press release or authorize the publication or presentation of any Study Results without obtaining Oraya's prior written approval.