Study of ANX007 in Participants With Primary Open-angle Glaucoma

A Phase 1b, Randomized, Double-masked, Sham-controlled Study of ANX007 Administered as Intravitreal Injections to Assess Safety and Tolerability in Participants With Primary Open-angle Glaucoma

This is a double-masked, randomized, sham-controlled study evaluating two dose levels of ANX007 vs sham, administered as repeat Intravitreal (IVT) injections in patients with Primary Open-angle Glaucoma.

Study Overview

• Status: Completed
• Conditions: Open Angle Glaucoma
• Intervention / Treatment: Biological: 2.5mg ANX007; Biological: 5.0mg ANX007; Other: Sham Procedure

Detailed Description

This is a phase 1b, double-masked, sham-controlled study evaluating 2 dose levels of ANX007 administered as 2 IVT injections separated by 4 weeks. Approximately 15-29 subjects will be enrolled. An interim analysis of the initial set of 15 participants may be conducted. Based on this analysis, an additional 10-14 participants may be enrolled at a 1:1 ratio to receive one of the two dose levels.

The primary objective is to evaluate the safety and tolerability of repeat IVT injections of ANX007 in participants with primary open-angle glaucoma. Secondary objectives are to evaluate the anterior chamber fluid pharmacokinetics (PK) of ANX007, PD effect of ANX007 on anterior chamber fluid C1q activity, and immunogenicity. An exploratory objective will evaluate ocular PD effect of ANX007.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Newport Beach, California, United States, 94303
      • Eye Research Foundation
    • Stanford, California, United States, 94305
      • Stanford Health Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female age 18 years, and above.
2. Diagnosis of primary open-angle glaucoma.
3. Ability to perform a reliable visual field test in the study eye with a cutoff of 33% for fixation losses and 33% for false-positive response rates.
4. Intraocular pressure (IOP) <21 mm Hg at screening and Day 1.
5. The IOP treatment regimen in the study eye should be stable for at least 4 weeks prior to injection, with no change in the IOP treatment regimen anticipated throughout study participation.
6. Ability to comply with the requirements of the study and complete the full sequence of protocol specified injections, procedures, and evaluations.

Exclusion Criteria:

1. Extensive glaucomatous visual-field damage with a mean deviation worse than -18 dB on Humphrey visual field testing.
2. Any current or prior ocular pathology, other than glaucoma, which could interfere with the conduct of the study including, but not limited to, retinal or optic nerve disease and media opacity in the study eye.
3. History of intraocular inflammatory or infectious eye disease in the study eye.
4. Ocular trauma in the study eye within the preceding 6 months.
5. A history of uncomplicated cataract surgery less than 3 months prior to injection, or trabeculectomy, iridotomy, or other ocular procedures in the study eye that could affect drug distribution and excretion.
6. Any abnormality preventing reliable tonometry in the study eye.
7. Concurrent use of glucocorticoid medications administered by any ocular or systemic route. Nasal, inhaled, and dermatologic (if not administered around the eyes) glucocorticoids are permitted.
8. Receiving monoamine oxidase inhibitor therapy or patient-reported hypersensitivity to any component of apraclonidine, brimonidine, clonidine, phenylephrine, povidone iodine, proparacaine, or ANX007.
9. Active or history of malignancy within the past 5 years with the exception of curatively treated, basal cell carcinoma.
10. Previous treatment with another humanized monoclonal antibody, Fab or Fab'2.
11. History of any autoimmune or neurologic disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 2.5mg ANX007; 1 in every 3 subjects will be randomized to 2.5mg dose of ANX007.	Biological: 2.5mg ANX007; A single dose of 2.5mg ANX007 will be administered via IVT injection into the study eye at Day 1 and Day 29.
EXPERIMENTAL: 5.0mg ANX007; 1 in every 3 subjects will be randomized to 5.0mg dose of ANX007.	Biological: 5.0mg ANX007; A single dose of 5.0mg ANX007 will be administered via IVT injection into the study eye at Day 1 and Day 29.
SHAM_COMPARATOR: Sham Procedure; 1 in every 3 subjects will have a sham procedure performed instead of receiving ANX007.	Other: Sham Procedure; The sham injection is preformed by applying pressure to the eye at the location of a typical IVT injection using the blunt end of a syringe without a needle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To evaluate the safety and tolerability of ANX007 in participants with primary open-angle glaucoma as measured by occurrence of treatment-emergent adverse events.	Day 85

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate PK parameters of ANX007 in serum after repeat injections	Maximum Serum Concentration (Cmax) of ANX007	Day 29
Evaluate PK parameters of ANX007 in serum after repeat injections	Area Under the Curve (AUC) of ANX007	Day 29
Evaluate PK parameters of ANX007 in aqueous humor after repeat intravitreal injections	Maximum aqueous humor Concentration (Cmax) of ANX007	Day 29
Evaluate PK parameters of ANX007 in aqueous humor after repeat intravitreal injections	Aqueous humor Area Under the Curve (AUC) of ANX007	Day 29
Evaluate PD parameters of ANX007 in aqueous humor after repeat intravitreal injections	Maximum C1q concentration (Cmax) in aqueous humor	Day 29
Evaluate PD parameters of ANX007 in aqueous humor after repeat intravitreal injections	C1q area under the curve (AUC) in aqueous humor	Day 29
Evaluate PD parameters of ANX007 in serum after repeat intravitreal injections	Maximum C1q concentration (Cmax) in serum	Day 29
Evaluate PD parameters of ANX007 in serum after repeat intravitreal injections	C1q concentration area under the curve (AUC) in serum	Day 29
Immunogenicity of ANX007 as measured by serum anti-drug antibodies (ADA) after repeat intravitreal injections of ANX007	Incidence of positive antibody titre against ANX007 in serum	Day 84

Collaborators and Investigators

• Sponsor: Annexon, Inc.
• Investigators: Study Director: Eric Humphriss, Annexon Biosciences

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 25, 2018
• Primary Completion (ACTUAL): June 3, 2019
• Study Completion (ACTUAL): June 3, 2019

Study Registration Dates

• First Submitted: December 13, 2018
• First Submitted That Met QC Criteria: December 4, 2019
• First Posted (ACTUAL): December 5, 2019

Study Record Updates

• Last Update Posted (ACTUAL): August 20, 2020
• Last Update Submitted That Met QC Criteria: August 19, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Ocular Hypertension; Glaucoma; Glaucoma, Open-Angle
• Other Study ID Numbers: ANX007-GLA-02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No