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A Study of the Efficacy and Safety of Brolucizumab vs. Aflibercept in Patients With Visual Impairment Due to Diabetic Macular Edema (KITE)

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ClinicalTrials.gov Identifier: NCT03481660
Recruitment Status : Not yet recruiting
First Posted : March 29, 2018
Last Update Posted : June 20, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
The purpose of this study is to evaluate the efficacy and safety of brolucizumab in treatment of patients with visual impairment due to diabetic macular edema (DME).

Condition or disease Intervention/treatment Phase
Diabetic Macular Edema Drug: Brolucizumab Drug: Aflibercept Phase 3

Detailed Description:
In this 2-year, randomized, double-masked, multicenter, active controlled study, consenting patients will be randomized in a 1:1 ratio to one of the two treatment arms and attend 28 planned visits.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 356 participants
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Two-Year, Two-Arm, Randomized, Double Masked, Multicenter, Phase III Study Assessing the Efficacy and Safety of Brolucizumab Versus Aflibercept in Adult Patients With Visual Impairment Due to Diabetic Macular Edema
Estimated Study Start Date : August 2, 2018
Estimated Primary Completion Date : July 15, 2020
Estimated Study Completion Date : July 22, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Edema

Arm Intervention/treatment
Experimental: Brolucizumab 6 mg
Brolucizumab 6 mg/0.05 mL, 5 loading doses, with subsequent doses per protocol-specified maintenance schedule
Drug: Brolucizumab
Intravitreal injection
Other Name: RTH258, ESBA1008

Active Comparator: Aflibercept 2 mg
Aflibercept 2 mg/0.05 mL, as labeled, 5 loading doses, with subsequent doses every 8 weeks
Drug: Aflibercept
Intravitreal injection
Other Name: Eylea




Primary Outcome Measures :
  1. Change from baseline in best-corrected visual acuity (BCVA) at Week 52 [ Time Frame: Baseline, Week 52 ]
    BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts


Secondary Outcome Measures :
  1. Average change from baseline in BCVA over the period Week 40 through Week 52 [ Time Frame: Baseline up to Week 52 ]
    Assessed with ETDRS visual acuity testing charts

  2. Proportion of patients maintained at q12w up to Weeks 52 and 100 [ Time Frame: Up to Week 100 ]
    Positive treatment status is defined as IVT injections per planned dosing regimen [every 12 weeks (q12w)]. This outcome measure is pre-specified for brolucizumab treatment arm only.

  3. Proportion of patients maintained at q12w up to Week 52 within those patients that qualified for q12w at Week 36 [ Time Frame: Up to Week 52 ]
    This outcome measure is pre-specified for brolucizumab treatment arm only.

  4. Change from baseline in BCVA at each visit up to Week 100 [ Time Frame: Baseline up to Week 100 ]
    Assessed with ETDRS visual acuity testing charts

  5. Average change from baseline in BCVA over the period Week 4 to Week 52/100 [ Time Frame: Baseline up to Week 100 ]
    Assessed with ETDRS visual acuity testing charts

  6. Average change from baseline in BCVA over the period Week 20 to Week 52/100 and Week 28 to Week 52/100 [ Time Frame: Baseline up to Week 100 ]
    Assessed with ETDRS visual acuity testing charts

  7. Gain in BCVA of ≥5, ≥10, and ≥15 ETDRS letters from baseline to each post-baseline visit [ Time Frame: Baseline up to Week 100 ]
    Assessed with ETDRS visual acuity testing charts

  8. Time to achieve gain in BCVA of ≥5, ≥10, and ≥15 ETDRS letters from baseline (or reaching a score of 84 or more) [ Time Frame: Baseline up to Week 100 ]
    Assessed with ETDRS visual acuity testing charts

  9. Loss in BCVA of ≥5, ≥10, and ≥15 ETDRS letters from baseline to each post-baseline visit [ Time Frame: Baseline up to Week 100 ]
    Assessed with ETDRS visual acuity testing charts

  10. Absolute BCVA ≥73 ETDRS letters at each post-baseline visit [ Time Frame: Baseline up to Week 100 ]
    Assessed with ETDRS visual acuity testing charts

  11. Proportion of patients maintained at q12w up to Week 64 (after three q12w- treatment intervals) [ Time Frame: Up to Week 64 ]
  12. Proportion of patients maintained at q12w up to Week 64 (after three q12w- treatment intervals), within those patients that qualified for q12w at Week 36 [ Time Frame: Up to Week 64 ]
    This outcome measure is pre-specified for brolucizumab treatment arm only

  13. Proportion of patients maintained at q12w/q16w up to Week 100, within those patients that qualified for q12w at Week 36 [ Time Frame: Up to Week 100 ]
    This outcome measure is pre-specified for brolucizumab treatment arm only

  14. Proportion of patients with disease activity at Week 32 (eg ≥5 letters loss in BCVA compared to Week 28) [ Time Frame: Week 28, Week 32 ]
    This outcome measure is pre-specified for brolucizumab treatment arm only

  15. Proportion of patients maintained on q16w up to Week 100 within the patients on q12 at Week 68 and on q16w at Week 76 [ Time Frame: Up to Week 100 ]
  16. Proportion of patients re-assigned and maintained on q12w up to Week 100 within the patients on q8w at Week 68 and on q12w at Week 80 [ Time Frame: Up to Week 100 ]
  17. Proportion of patients with injections per planned dosing regimen (every 8, 12 or 16 weeks) [ Time Frame: Up to Week 100 ]
    This outcome measure is pre-specified for brolucizumab treatment arm only

  18. Change from baseline in central subfield thickness (CSFT) at each assessment visit [ Time Frame: Baseline up to Week 100 ]
    Assessed by Spectral Domain Optical Coherence Tomography (SD-OCT)

  19. Average change from baseline in CSFT over the period Week 40 through Week 52 / Week 88 through Week 100 [ Time Frame: Baseline up to Week 100 ]
    Assessed by SD-OCT

  20. Average change from baseline in CSFT over the period Week 4 to Week 52 / 96 [ Time Frame: Baseline up to Week 96 ]
    Assessed by SD-OCT

  21. Patient status regarding normal CSFT thickness (<280 microns) at each assessment visit [ Time Frame: Baseline up to Week 100 ]
    Assessed by SD-OCT

  22. Change from baseline in central subfield thickness-neurosensory (CSFTns) at each assessment visit [ Time Frame: Baseline up to Week 100 ]
    Assessed by SD-OCT

  23. Average change from baseline in CSFTns over the period Week 40 through Week 52 / Week 88 through Week 100 [ Time Frame: Baseline up to Week 100 ]
    Assessed by SD-OCT

  24. Average change from baseline in CSFTns over the period Week 4 to Week 52 / 100 [ Time Frame: Baseline up to Week 100 ]
  25. Proportion of patients with presence of subretinal fluid (SRF) at each assessment visit [ Time Frame: Baseline up to Week 100 ]
    Assessed by SD-OCT, angiography, and/or color fundus photography

  26. Proportion of patients with presence of intraretinal fluid (IRF) at each assessment visit [ Time Frame: Baseline up to Week 100 ]
    Assessed by SD-OCT, angiography, and/or color fundus photography

  27. Proportion of patients with simultaneous absence of SRF and IRF at each assessment visit [ Time Frame: Baseline up to Week 100 ]
    Assessed by SD-OCT, angiography, and/or color fundus photography

  28. Proportion of patients with presence of leakage on fluorescein angiography (FA) at Weeks 52 and 100 [ Time Frame: Up to Week 100 ]
    Assessed by fluorescein angiography

  29. Change from baseline in ETDRS Diabetic Retinopathy Severity Scale (ETDRS-DRSS) score at each assessment visit [ Time Frame: Baseline up to Week 100 ]
    The Diabetic Retinopathy Disease Severity Scale measures the 5 levels of diabetic retinopathy - none, mild, moderate, severe, and proliferative

  30. Number of patients with progression to proliferative diabetic retinopathy (PDR) as assessed by ETDRS-DRSS Score of at least 61 by Week 52 and Week 100 [ Time Frame: Baseline up to Week 100 ]
    ETDRS-DRSS

  31. Change from baseline in patient reported outcomes (VFQ-25) total and subscale scores up to Week 100 [ Time Frame: Baseline up to Week 100 ]
    The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains

  32. Systemic brolucizumab/aflibercept concentration [ Time Frame: Up to Week 24 ]
    Blood draw

  33. Anti-Drug Antibody (ADA) status [ Time Frame: Up to Week 100 ]
    Blood draw

  34. Average change from baseline in BCVA from the period Week 88 to 100 [ Time Frame: Baseline up to Week 100 ]
    Assessed with ETDRS visual acuity testing charts



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent before any assessment
  • Patients with type 1 or type 2 diabetes mellitus and HbA1c of ≤10% at screening
  • Medication for the management of diabetes stable within 3 months prior to randomization and is expected to remain stable during the course of the study

Exclusion Criteria:

  • Active proliferative diabetic retinopathy in the study eye
  • Active intraocular or periocular infection or active intraocular inflammation in the study eye
  • Uncontrolled glaucoma in the study eye defined as intraocular pressure (IOP) > 25 millimeters mercury (mmHg)
  • Previous treatment with anti-VEGF drugs or investigational drugs in the study eye
  • Stroke or myocardial infarction during the 6-month period prior to baseline
  • Uncontrolled blood pressure defined as a systolic value ≥160 mmHg or diastolic value ≥100 mmHg

Other protocol-specified inclusion/exclusion criteria may apply


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03481660


Contacts
Contact: Novartis Pharmaceuticals +41613241111 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals

Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03481660     History of Changes
Other Study ID Numbers: CRTH258B2302
2017-003960-11 ( EudraCT Number )
First Posted: March 29, 2018    Key Record Dates
Last Update Posted: June 20, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on ww.clinicalstudydatarequest.com.

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

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Diabetic Macular Edema
intravitreal injection
brolucizumab
aflibercept
double-masked

Additional relevant MeSH terms:
Vision, Low
Edema
Macular Edema
Vision Disorders
Signs and Symptoms
Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases