A Research Study to Look at How Semaglutide Compared to Placebo Affects Diabetic Eye Disease in People With Type 2 Diabetes (FOCUS)

• ClinicalTrials.gov Identifier: NCT03811561
• Recruitment Status: Recruiting
• First Posted: January 22, 2019
• Last Update Posted: January 14, 2021
• Sponsor: Novo Nordisk A/S
• Information provided by (Responsible Party): Novo Nordisk A/S

Tracking Information

• First Submitted Date: January 18, 2019
• First Posted Date: January 22, 2019
• Last Update Posted Date: January 14, 2021
• Actual Study Start Date: May 8, 2019
• Estimated Primary Completion Date: July 13, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 18, 2019)

Presence of at least 3 steps Early Treatment Diabetic Retinopathy Study (ETDRS) subject level progression. [ Time Frame: Year 5 ]

Percentage of subjects (yes/no).

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 23, 2019)

• Time from randomisation to first at least 3 steps ETDRS subject level progression or central involved diabetic macular oedema (ciDME) in either eye. [ Time Frame: Up to 5 years ]
  Measured in months.
• Change in visual acuity in the worse seeing eye. [ Time Frame: Week 0, Year 5 ]
  Measured in number of letters using the ETDRS protocol.
• Change in visual acuity in the better seeing eye. [ Time Frame: Week 0, Year 5 ]
  Measured in number of letters using the ETDRS protocol.
• Occurrence of treatment for diabetic retinopathy or diabetic macular oedema in either eye with focal/grid laser photocoagulation. [ Time Frame: Week 0-Year 5 ]
  Percentage of subjects (yes/no).
• Occurrence of treatment for diabetic retinopathy or diabetic macular oedema in either eye with pan-retinal laser photocoagulation. [ Time Frame: Week 0-Year 5 ]
  Percentage of subjects (yes/no).
• Occurrence of treatment for diabetic retinopathy or diabetic macular oedema in either eye with intravitreal injection with anti-vascular endothelial growth factor (VEGF). [ Time Frame: Week 0-Year 5 ]
  Percentage of subjects (yes/no).
• Occurrence of treatment for diabetic retinopathy or diabetic macular oedema in either eye with intravitreal injection with steroid. [ Time Frame: Week 0-Year 5 ]
  Percentage of subjects (yes/no).
• Occurrence of treatment for diabetic retinopathy or diabetic macular oedema in either eye with vitrectomy. [ Time Frame: Week 0-Year 5 ]
  Percentage of subjects (yes/no).
• Presence of at least 3 steps ETDRS subject level improvement. [ Time Frame: Year 5 ]
  Percentage of subjects (yes/no).
• Presence of at least 2 steps ETDRS subject level progression. [ Time Frame: Year 5 ]
  Percentage of subjects (yes/no).
• Presence of at least 2 steps ETDRS subject level improvement. [ Time Frame: Year 5 ]
  Percentage of subjects (yes/no).
• Presence of persistent visual acuity up to 38 ETDRS letters in either eye. [ Time Frame: Year 5 ]
  Percentage of subjects (yes/no).
• Presence of persistent at least 2 lines (10 letters) ETDRS worsening in visual acuity in either eye from baseline. [ Time Frame: Year 5 ]
  Percentage of subjects (yes/no).
• Presence of persistent at least 3 lines (15 letters) ETDRS worsening in visual acuity in either eye from baseline. [ Time Frame: Year 5 ]
  Percentage of subjects (yes/no).
• Presence of persistent at least 2 lines (10 letters) ETDRS improvement in visual acuity in either eye from baseline. [ Time Frame: Year 5 ]
  Percentage of subjects (yes/no).
• Persistent at least 3 lines (15 letters) ETDRS improvement in visual acuity in either eye from baseline. [ Time Frame: Year 5 ]
  Percentage of subjects (yes/no).
• Presence of ciDME in either eye. [ Time Frame: Year 5 ]
  Percentage of subjects (yes/no).
• Change in glycosylated haemoglobin (HbA1c). [ Time Frame: Week 0, Year 5 ]
  Measured in %-points.
• Change in body weight. [ Time Frame: Week 0, Year 5 ]
  Measured in kg.
• Change in systolic and diastolic blood pressure. [ Time Frame: Week 0, Year 5 ]
  Measured in mmHg.
• Change in Lipids: Total-cholesterol, High density lipoprotein (HDL)-cholesterol, low density lipoprotein (LDL)-cholesterol and triglycerides. [ Time Frame: Week 0, Year 5 ]
  Measured in mmol/L

Original Secondary Outcome Measures (submitted: January 18, 2019)

• Time from randomisation to first at least 3 steps ETDRS subject level progression or central involved diabetic macular oedema (ciDME) in either eye. [ Time Frame: Up to 5 years ]
  Measured in months.
• Change in visual acuity in the worse seeing eye. [ Time Frame: Week 0, Year 5 ]
  Measured in number of letters using the ETDRS protocol.
• Change in visual acuity in the better seeing eye. [ Time Frame: Week 0, Year 5 ]
  Measured in number of letters using the ETDRS protocol.
• Occurrence of treatment for diabetic retinopathy or diabetic macular oedema in either eye with focal/grid laser photocoagulation. [ Time Frame: Week 0-Year 5 ]
  Percentage of subjects (yes/no).
• Occurrence of treatment for diabetic retinopathy or diabetic macular oedema in either eye with pan-retinal laser photocoagulation. [ Time Frame: Week 0-Year 5 ]
  Percentage of subjects (yes/no).
• Occurrence of treatment for diabetic retinopathy or diabetic macular oedema in either eye with intravitreal injection with anti-vascular endothelial growth factor (VEGF). [ Time Frame: Week 0-Year 5 ]
  Percentage of subjects (yes/no).
• Occurrence of treatment for diabetic retinopathy or diabetic macular oedema in either eye with intravitreal injection with steroid. [ Time Frame: Week 0-Year 5 ]
  Percentage of subjects (yes/no).
• Occurrence of treatment for diabetic retinopathy or diabetic macular oedema in either eye with vitrectomy. [ Time Frame: Week 0-Year 5 ]
  Percentage of subjects (yes/no).
• Presence of at least 3 steps ETDRS subject level improvement. [ Time Frame: Year 5 ]
  Percentage of subjects (yes/no).
• Presence of at least 2 steps ETDRS subject level progression. [ Time Frame: Year 5 ]
  Percentage of subjects (yes/no).
• Presence of at least 2 steps ETDRS subject level improvement. [ Time Frame: Year 5 ]
  Percentage of subjects (yes/no).
• Presence of persistent visual acuity up to 38 ETDRS letters in either eye. [ Time Frame: Year 5 ]
  Percentage of subjects (yes/no).
• Presence of persistent at least 2 lines (10 letters) ETDRS worsening in visual acuity in either eye from baseline. [ Time Frame: Year 5 ]
  Percentage of subjects (yes/no).
• Presence of persistent at least 3 lines (15 letters) ETDRS worsening in visual acuity in either eye from baseline. [ Time Frame: Year 5 ]
  Percentage of subjects (yes/no).
• Presence of persistent at least 2 lines (10 letters) ETDRS improvement in visual acuity in either eye from baseline. [ Time Frame: Year 5 ]
  Percentage of subjects (yes/no).
• Persistent at least 3 lines (15 letters) ETDRS improvement in visual acuity in either eye from baseline. [ Time Frame: Year 5 ]
  Percentage of subjects (yes/no).
• Presence of ciDME in either eye. [ Time Frame: Year 5 ]
  Percentage of subjects (yes/no).
• Change in glycosylated haemoglobin (HbA1c). [ Time Frame: Week 0, Year 5 ]
  Measured in %-points.
• Change in body weight. [ Time Frame: Week 0, Year 5 ]
  Measured in kg.
• Change in systolic and diastolic blood pressure. [ Time Frame: Week 0, Year 5 ]
  Measured in mmHg.
• Change in Lipids: Total-cholesterol, High density lipoprotein (HDL)-cholesterol, low density lipoprotein (LDL)-cholesterol and triglycerides. [ Time Frame: Week 0, Year 5 ]
  Meaured in mmol/L

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Research Study to Look at How Semaglutide Compared to Placebo Affects Diabetic Eye Disease in People With Type 2 Diabetes
• Official Title: Long-term Effects of Semaglutide on Diabetic Retinopathy in Subjects With Type 2 Diabetes
• Brief Summary: This study will look at the long-term effects of semaglutide (active medicine) on diabetic eye disease when compared to placebo (dummy medicine). The study will be performed in people with type 2 diabetes. Participants will either get semaglutide or placebo in addition to their diabetes medicines - which treatment the participant gets is decided by chance. Participants will inject the study medicine using a pen-injector. The medicine must be injected in a skin fold in the stomach, thigh or upper arm once a week. The study will last for 5 years.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Sponsor staff involved in the clinical trial is masked according to company standard procedures.

Primary Purpose: Treatment

• Condition: Diabetes Mellitus, Type 2

Intervention

• Drug: Semaglutide
  Participants will get one dose of semaglutide once weekly in addition to their diabetes medicines - which treatment they get is decided by chance. Participants will inject the study medicine using a pre-filled PDS290 pen-injector. The medicine must be injected in a skin fold in the stomach, thigh or upper arm once a week. Participants will start with once-weekly doses of 0.25 mg for 4 weeks, then the dose will be gradually increased to 0.5 mg once weekly for 4 weeks, and finally to 1.0 mg once weekly (maximum dose) up to 260 weeks (5 years).
• Drug: Placebo (semaglutide)
  Participants will get one dose of placebo (semaglutide) once weekly in addition to their diabetes medicines - which treatment they get is decided by chance. Participants will inject the study medicine using a pre-filled PDS290 pen-injector. The medicine must be injected in a skin fold in the stomach, thigh or upper arm once a week. Participants will start with once-weekly doses of 0.25 mg for 4 weeks, then the dose will be gradually increased to 0.5 mg once weekly for 4 weeks, and finally to 1.0 mg once weekly (maximum dose) up to 260 weeks (5 years).

Study Arms

• Experimental: Semaglutide
  Participants will receive semaglutide once weekly as subcutaneous (s.c., under the skin) injection added to standard of care.
  Intervention: Drug: Semaglutide
• Placebo Comparator: Placebo
  Participants will receive placebo (semaglutide) once weekly as subcutaneous subcutaneous (s.c., under the skin) injection added to standard of care.
  Intervention: Drug: Placebo (semaglutide)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 18, 2019): 1500
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 18, 2026
• Estimated Primary Completion Date: July 13, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Male or female, age greater than or equal to 18 years at the time of signing informed consent
• Diagnosed with type 2 diabetes mellitus.
• HbA1c of 7.0-10.0% (53-86 mmol/mol) (both inclusive).
• Eye inclusion criteria (both eyes must meet all criteria):
• Early Treatment Diabetic Retinopathy Study (ETDRS) level of 10-75 (both inclusive) evaluated by fundus photography and confirmed by central reading centre
• No ocular or intraocular treatment for diabetic retinopathy or diabetic macular oedema six months prior to the day of screening.
• No anticipated need for ocular or intraocular treatment for diabetic retinopathy or diabetic macular oedema within three months after randomisation.
• Best-corrected visual acuity greater than or equal to 30 letters using the ETDRS visual acuity protocol
• No previous treatment with pan-retinal laser photocoagulation
• No substantial non-diabetic ocular condition that, in the opinion of the ophthalmologist, would impact diabetic retinopathy or diabetic macular oedema progression during the trial
• No substantial media opacities that would preclude successful imaging

Exclusion Criteria:

• Any of the following: myocardial infarction, stroke, hospitalization for unstable angina pectoris or transient ischaemic attack within the past 60 days prior to the day of screening
• Planned coronary, carotid or peripheral artery revascularisation known on the day of screening
• Subjects presently classified as being in New York Heart Association (NYHA) Class IV
• Renal impairment measured as estimated Glomerular Filtration Rate (eGFR) value of eGFR less than 30 ml/min/1.73 m^2
• Personal or first degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma
• Presence or history of malignant neoplasms within the past 5 years prior to the day of screening. Basal and squamous cell skin cancer and any carcinoma in-situ are allowed
• Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using highly effective contraceptive methods
• Concurrent treatment with any GLP-1 receptor agonist or DPP-4 inhibitor from randomisation.
• Receipt of any investigational medicinal product within 30 days before screening
• Previous participation in this trial. Participation is defined as randomisation
• Known or suspected hypersensitivity to trial products or related products
• Any disorder, which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Novo Nordisk; +1 866-867-7178; clinicaltrials@novonordisk.com

• Listed Location Countries: Brazil, Bulgaria, Canada, Czechia, Germany, India, Israel, Latvia, Mexico, Poland, Portugal, Romania, Russian Federation, Serbia, Slovakia, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT03811561
• Other Study ID Numbers: NN9535-4352; U1111-1201-6256 ( Other Identifier: World Health Organization (WHO) ); 2017-003619-20 ( Registry Identifier: European Medicines Agency (EudraCT) )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
• URL: http://novonordisk-trials.com

• Responsible Party: Novo Nordisk A/S
• Study Sponsor: Novo Nordisk A/S
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Reporting Anchor and Disclosure (1452); Novo Nordisk A/S

• PRS Account: Novo Nordisk A/S
• Verification Date: January 2021