Safety and Efficacy of IONIS-FB-Lrx in up to 120 Patients 55 and Older With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (AMD)

Sponsor

Ionis Pharmaceuticals, Inc. (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT03446144

Collaborator

(none)

Enrollment

Locations

Arms

6.8

Actual Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the Safety and Efficacy of IONIS-FB-Lrx for up to 120 patients with Geographic Atrophy secondary to Age Related Macular Degeneration

Condition or Disease	Intervention/Treatment	Phase
Geographic Atrophy Age Related Macular Degeneration	Drug: IONIS-FB-Lrx Drug: Placebo (sterline saline 0.9%)	Phase 2

Detailed Description

This study will assess changes in complement factor B over a 69-week treatment period in a patient population 55 and older with well-demarcated Geographic Atrophy secondary to Age Related Macular Degeneration

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Masking Description:

Double Masked

Primary Purpose:

Treatment

Official Title:

A Phase 2, Placebo-Controlled, Double-Masked Study to Assess Safety and Efficacy of ISIS 696844, an Antisense Inhibitor of Complement Factor B, in Patients With Geographic Atrophy Secondary (GA) to Age-Related Macular Degeneration (AMD)

Actual Study Start Date :

Mar 16, 2018

Actual Primary Completion Date :

Oct 10, 2018

Actual Study Completion Date :

Oct 10, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IONIS-FB-Lrx	Drug: IONIS-FB-Lrx Single Dose of IONIS-FB-Lrx administered once weekly for weeks 1-3, and every other week or less frequently until week 70
Placebo Comparator: Placebo (sterile saline 0.9%)	Drug: Placebo (sterline saline 0.9%) Calculated volume to match active comparator. Administered subcutaneously weekly for weeks 1-3, and every other week or less frequently until week 70

Arm

Intervention/Treatment

Experimental: IONIS-FB-Lrx

Drug: IONIS-FB-Lrx

Single Dose of IONIS-FB-Lrx administered once weekly for weeks 1-3, and every other week or less frequently until week 70

Placebo Comparator: Placebo (sterile saline 0.9%)

Drug: Placebo (sterline saline 0.9%)

Calculated volume to match active comparator. Administered subcutaneously weekly for weeks 1-3, and every other week or less frequently until week 70

Outcome Measures

Primary Outcome Measures

Efficacy of IONIS-FB-Lrx [Up to 74 weeks]
The Efficacy of IONIS-FB-Lrx will be measured by the percent change in plasma complement factor B level

Secondary Outcome Measures

Incidence and severity of adverse events that are related to treatment with IONIS-FB-Lrx [Up to 86 weeks]
The safety and tolerability of IONIS-FB-Lrx will be assessed by determining the incidence and severity of adverse events that are related to treatment with IONIS-FB-Lrx
Proportion of patients in each treatment group achieving a >50% reduction of plasma complement factor B [Up to 74 weeks]
Proportion of patients in each treatment group achieving a >50% reduction of plasma complement factor B from Baseline to Post-Treatment
Effect of IONIS-FB-Lrx on the rate of change of the area of GA secondary to AMD [Up to 74 weeks]
Effect of IONIS-FB-Lrx on the rate of change of the area of GA secondary to AMD as measured by Fundus Autofluorescence from Baseline to Post-Treatment
Effect of factor B reduction on other components of the complement pathways in AMD patients [Up to 74 weeks]
Effect of factor B reduction on other components of the complement pathways such as AH50, CH50 and Bb in AMD patients from Baseline to Post-Treatment

Eligibility Criteria

Criteria

Ages Eligible for Study:

55 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Must have given written informed consent and be able to comply with study requirements
Females must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal. Males must be surgically sterile or, if engaged in sexual relations with a female of child bearing potential, the subject must be using an acceptable contraceptive method from the time of signing the informed consent form until at least a period of 13 weeks after the last dose of Study Drug (ISIS 696844 or placebo)
Well-demarcated Geographic Atrophy due to Age Related Macular Degeneration

Key Exclusion Criteria:

Clinically-significant abnormalities in medical history
Diagnosis of primary or secondary immunodeficiencies of B lymphocyte function, splenectomy, glomerulonephritis or history of recurrent meningococcal disease
Diabetes mellitus or thyroid disease unless well controlled for a period of at least 3 months
Clinically-significant abnormalities in screening laboratory values
Unwillingness to be administered, or history of a serious reaction to protocol required vaccines
Known history of or positive test for human immunodeficiency virus (HIV), hepatitis C or chronic hepatitis B
History or presence of a disease other than AMD in study eye

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	IONIS Investigative Site	Phoenix	Arizona	United States	85014-2709
2	IONIS Investigational Site	Beverly Hills	California	United States	90211
3	IONIS Investigative Site	Encino	California	United States	91436
4	IONIS Investigative Site	Irvine	California	United States	92697
5	IONIS Investigational Site	Mountain View	California	United States	94040
6	IONIS Investigational Site	Santa Barbara	California	United States	93103
7	IONIS Investigative Site	Clearwater	Florida	United States	33761
8	IONIS Investigational Site	Tampa	Florida	United States	33612
9	IONIS Investigational Site	Augusta	Georgia	United States	30909
10	IONIS Investigational Site	Leawood	Kansas	United States	66211
11	IONIS Investigative Site	Chesterfield	Missouri	United States	63017
12	IONIS Investigative Site	New York	New York	United States	10021
13	IONIS Investigative Site	Philadelphia	Pennsylvania	United States	19104
14	IONIS Investigative Site	Philadelphia	Pennsylvania	United States	19107-5109
15	IONIS Investigative Site	Pittsburgh	Pennsylvania	United States	15213
16	IONIS Investigational Site	Ladson	South Carolina	United States	29456
17	IONIS Investigative Site	Rapid City	South Dakota	United States	57701-7374
18	IONIS Investigative Site	Arlington	Texas	United States	76012-2505
19	IONIS Investigational Site	Austin	Texas	United States	78705
20	IONIS Investigative Site	Dallas	Texas	United States	75231-5078
21	IONIS Investigative Site	Houston	Texas	United States	77030-2727
22	IONIS Investigative Site	McAllen	Texas	United States	78503-1518
23	IONIS Investigative Site	San Antonio	Texas	United States	78240-1502
24	IONIS Investigative Site	The Woodlands	Texas	United States	77384-8018
25	Eye Clinic Albury Wodonga	Albury	New South Wales	Australia	2640
26	IONIS Investigational Site	Liverpool	New South Wales	Australia	2170
27	Marsden Eye Specialists	Paramatta	New South Wales	Australia	2150
28	Strathfield Retina Clinic	Strathfield	New South Wales	Australia	2135
29	Sydney Eye Hospital	Sydney	New South Wales	Australia	2000
30	Sydney Retina Clinic Day Surgery	Sydney	New South Wales	Australia	2000
31	Royal Adelaide Hospital	Adelaide	South Australia	Australia	5000
32	The Royal Victorian Eye and Ear Hospital	East Melbourne	Victoria	Australia	3002
33	Retinology Institute	Glen Iris	Victoria	Australia	3146
34	Eye Surgery Associates	Malvern	Victoria	Australia	3144
35	Eye Surgery Associates	Parkville	Victoria	Australia	3050
36	Lions Eye Institute	Nedlands	Western Australia	Australia	6009
37	Auckland Eye	Auckland		New Zealand	1050