A Study Investigating Oral Semaglutide in People with Open-Angle Glaucoma (ABSALON)

Additive Benefits of Semaglutide for Open-AngLe Glaucoma - an Opportunity for Neuroprotection

The aim of this clinical trial is to investigate whether oral semaglutide can be used to treat open-angle glaucoma. The main question it aims to answer is: Does oral semaglutide safely improve inner retinal function in patients with open-angle glaucoma as measured by the photopic negative response of the electroretinogram.

Researchers will compare oral semaglutide to a placebo (a look-alike substance that contains no drug).

Participants will:

• Take semaglutide or a placebo every day for 6 months.
• Visit the clinic 5 times in total for tests and interviews: At baseline (the first day they are included in the study), after 1 month, after 2 months, after 3 months, and after 6 months (the last day they are included in the study).

Study Overview

• Status: Recruiting
• Conditions: Glaucoma; Open-Angle Glaucoma; Primary Open Angle Glaucoma (POAG)
• Intervention / Treatment: Drug: Oral semaglutide; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 126
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Miriam Kolko, MD, PhD; Phone Number: +45 29807667; Email: miriamk@sund.ku.dk
• Study Contact Backup: Name: Anna-Sophie Thein; Email: anna-sophie.thein@sund.ku.dk

Study Locations

• Denmark
  • Glostrup, Denmark, 2600
    • Recruiting
    • Department of Ophthalmology, Rigshospitalet
    • Contact: Miriam Kolko, MD, PhD, Professor, Consultant; Phone Number: +45 29807667; Email: miriamk@sund.ku.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Ability to read and speak Danish
• 45 years or older at the time of inclusion
• Visual acuity equal to or above 0.5 in the study eye
• Diagnosis of POAG with MD ≤ 16 dB with repeatable and reliable (false positive less than 15 %) VF loss measured by standard automated perimetry on at least one eye
• Receiving IOP-lowering glaucoma treatment
• Nerve fiber layer defects identified by OCT

Exclusion Criteria:

• Diabetes or renal impairment
• Medical history of significant eye disease (including ocular trauma) other than glaucoma
• Ocular inflammation/infection within three months from inclusion
• Intraocular surgery 3 months before inclusion
• Smoker at the time of inclusion
• Pregnant or breast-feeding
• Females of childbearing potential who are not using adequate contraceptive, which includes the following: Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, or transdermal, progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, or implantable; Intrauterine device (IUD); Intrauterine hormone-releasing system (IUS); Bilateral tubal occlusion; Vasectomised partner; Sexual abstinence
• Subjects allergic to drug ingredients administered during the trial
• Subjects with untreated severe systemic disease or malignancies
• Previous history of pancreatitis
• BMI < 18.5
• Subjects receiving treatment with: Dipeptidyl peptidase-4 inhibitors; Other GLP-1RAs; Insulin; Insulin analogues; Sulfonylurea; Systemic corticosteroids; Immunosuppressants

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oral Semaglutide; Participants are given oral semaglutide once daily.	Drug: Oral semaglutide; Participants will receive oral semaglutide once daily.; Starting dose 3 mg/day for one month (day 1-28); Intermediate dose 7 mg/day for one month (day 29-56); Maintenance dose 14 mg/day (day 57-182)
Placebo Comparator: Placebo; Participants are given oral placebo once daily.	Drug: Placebo; Participants will receive an oral placebo once daily.; Placebo tablets received on visit 1 (baseline) for one month (day 1-28); Placebo tablets received on visit 2 (month 1) for one month (day 29-56); Placebo tablets received on visit 3 (month 2) for four months (day 57-182)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Photopic negative response of the electroretinogram after 6 months	Change in the inner retinal function assessed by mean change in the photopic negative response of the electroretinogram.	From baseline to month 6.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Photopic negative response of the electroretinogram after 3 months	Change in the inner retinal function assessed by mean change in the photopic negative response of the electroretinogram.	From baseline to month 3.
Pelli-Robson chart contrast sensitivity test	Functional glaucoma progression assessed using the Pelli-Robson chart contrast sensitivity test.	From baseline to month 6.
Health-related quality of life (HRQoL)	Health-related quality of life (HRQoL) assessed with the European Quality of life - 5 Dimensions - 3 Levels (EQ-5D-3L) questionnaire, a standardized validated questionnaire administered in Danish. The EQ-5D-3L questionnaire comprises the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results into a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state.	From baseline to month 6.
Health-related quality of life (HRQoL)	Health-related quality of life (HRQoL) assessed with the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25), a standardized validated questionnaire administered in Danish. The scoring system for the NEI VFQ-25 generates 12 subscale scores and an overall composite score. A higher score indicates a higher level of functioning.	From baseline to month 6.
Number of treatment-related adverse events as assessed by CTCAE v5.0	Safety and tolerance of oral semaglutide treatment in patients with glaucoma assessed by the incidence of treatment-emergent adverse events (TEAEs) by CTCAE v5.0.	From baseline to month 6.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Optical coherence tomography (OCT), ring scan	Structural glaucoma progression assessed by the OCT ring scan, which measures the retinal nerve fibre layer thickness.	From baseline to month 6.
Optical coherence tomography (OCT), macular scan	Structural glaucoma progression assessed by the OCT macular scan which measures the volume of retinal ganglion cells.	From baseline to month 6.
Standard automated perimetry	Visual field loss will be evaluated using standard automated perimetry. Progression will be measured by changes in mean deviation (MD).	From baseline to month 6.
Multi-omics	Changes in the cytokine proteome will be assessed by changes in concentrations of glaucoma-associated cytokines as related to inflammation. Changes in the metabolome and lipidome will be assessed by changes in plasma metabolomics and lipidomics.	From baseline to month 6.

Collaborators and Investigators

• Sponsor: Glostrup University Hospital, Copenhagen

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2025
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: December 18, 2024
• First Submitted That Met QC Criteria: January 20, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 20, 2025
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: GLP-1; Semaglutide; Glaucoma; Primary Open Angle Glaucoma; GLP-1RA; Rybelsus; Photopic Negative Response
• Additional Relevant MeSH Terms: Eye Diseases; Ocular Hypertension; Glaucoma; Glaucoma, Open-Angle; Glucagon-Like Peptide-1 Receptor Agonists; Physiological Effects of Drugs; Hypoglycemic Agents; Semaglutide
• Other Study ID Numbers: 97669; NNF22OC0079544 (Other Grant/Funding Number: The Novo Nordisk Foundation); 2024-518510-87-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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