Comparison of Treatment rOutine Using afLibERcept: Strict vs relAxed retreatmeNT Regimen

NCT02550002 | Completed DMC

• 1 other identifier: TOLERANT
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 2

Brief Summary

The primary objective of this study is to test non-inferiority of aflibercept "treat and extend" using a relaxed retinal fluid management relative to aflibercept "treat and extend" using a strict retinal fluid management SD-OCT (spectral domain optical coherence tomography) disease activity guided retreatment with respect to best-corrected visual acuity (BCVA) from baseline to end of treatment.

Conditions

Age Related Macular Degeneration

Outcome Measures

Primary Outcomes (1)

• Change in best corrected visual acuity (BCVA) from baseline to end of treatment (EOS) at week 104. The primary outcome of the trial is the difference between the two arms in the mean change in BCVA from baseline to EOS.

  Change of BCVA from baseline to end of study at week 104

  From baseline to 24 months

Secondary Outcomes (7)

• The difference between the two arms in the mean change in BCVA from baseline to week 52.

  From baseline to 24 months

• The difference between the two arms in the mean change in central retinal thickness (CRT) from baseline to week 52 and to EOS.

  From baseline to 24 months

• The difference between the two arms in the mean number of injections from baseline to week 52 and to EOS.

  From baseline to 24 months

• The difference between the two arms in the proportion of patients showing newly developed geographic atrophy at week 52 and at EOS as compared to baseline.

  From baseline to 24 months

• The difference between the two arms in the mean change in the area of new and existing geographic atrophy from baseline to week 52 and to EOS.

  From baseline to 24 months

Study Arms (2)

Strict treatment regimen with aflibercept

Treatment intervals with aflibercept in the strict retinal fluid treatment regimen will be extended by two weeks only if no SRF in the central subfoveal field and no IRF can be detected SD-OCT examination.

Drug: Aflibercept

Relaxed treatment regimen with aflibercept

Treatment intervals with aflibercept in the relaxed retinal fluid treatment regimen will be extended by two weeks only if SRF in the central subfoveal field is ≤100 μm in a vertical extent and no IRF is detected on SD-OCT examination.

Drug: Aflibercept

Interventions

Aflibercept DRUG

Intravitreal injection

Also known as: Eylea

Relaxed treatment regimen with aflibercept; Strict treatment regimen with aflibercept

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

A total of 150 patients will be recruited to this study, with approximately 75 randomised to each study arm (relaxed and strict retinal fluid treatment regimen). Assuming an approximate 20% screen failure rate, approximately 188 patients will need to be screened to have 150 patients found eligible and commencing treatment in the trial.

You may qualify if:

• General:
• Informed consent as documented by signature of the patient on the informed consent form.
• Male or female, ≥50 years of age.
• Study eye:
• Diagnosis ofl CNV secondary to wAMD without restriction of lesion size, with visual impairment due to an active wAMD lesion. Active wAMD lesions are characterised by the following:
• Evidence of SRF and/or IRF and
• area of fibrosis less than 50% of the lesion area.
• CNV membrane confirmed by presence of active leakage from the area of CNV seen by fluorescein angiography (FA) and color fundus photography (CFP) and at least two of the following items:
• Drusen
• Retinal Pigment Epithelium (RPE)-Atrophy
• Exudates
• Subretinal or intraretinal haemorrhage
• BCVA scores at both screening and baseline must be 23 letters or more as measured by the ETDRS-like charts (or approximate Snellen equivalent to 20/320).

You may not qualify if:

• General:
• Inability to comply with study or follow-up procedures.
• Pregnant or nursing (lactating) women.
• Women of child-bearing potential, not using or not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the Investigator in individual cases. (Female participants who are surgically sterilised/hysterectomised, or post-menopausal for longer than 2 years are not considered as being of child-bearing potential.)
• Any type of systemic disease or its treatment, in the opinion of the Investigator, including any medical condition (controlled or uncontrolled) that could be expected to progress, recur, or change to such an extent that it may bias the assessment of the clinical status of the patient to a significant degree or put the patient at special risk.
• Stroke or myocardial infarction less than 3 months prior to the date of informed consent signature.
• Uncontrolled blood pressure defined as systolic value of \>160 mmHg or diastolic value of \>100 mmHg at screening or baseline.
• Known hypersensitivity to aflibercept or any component of the aflibercept formulation, or fluorescein.
• Prior or current use of any systemic anti-VEGF drugs \[e.g., bevacizumab (Avastin®) or ranibizumab (Lucentis®)\].
• Current or planned use of systemic medications known to be toxic to the lens, retina or optic nerve, including chloroquine/hydroxychloroquine (Plaquenil®), deferoxamine, phenothiazines, tamoxifen, and ethambutol.
• Use of systemic or intravitreal corticosteroids for at least 30 consecutive days within 3 months prior to the date of informed consent signature.
• Use of other investigational drugs within 6 months prior to the date of informed consent signature.
• Patient was previously screened for participation in the study and was a screen failure.
• Study eye:
• Any active periocular or ocular infection or inflammation (e.g., blepharitis, conjunctivitis, keratitis,scleritis, uveitis, endophthalmitis) at the time of screening or baseline.

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead

Study Sites (2)

Department of Ophthalmology, University Hospital Bern

Bern, 3010, Switzerland

Location

Inselspital Bern, Department of Ophthalmology

Bern, 3010, Switzerland

Location

Biospecimen

Retention: NONE RETAINED

blood

MeSH Terms

Conditions

Macular Degeneration

Interventions

aflibercept

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases

Study Officials

• Martin Zinkernagel, MD, PhD

  Inselspital Bern, Department of Ophthalmology

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2015
• First Posted: September 15, 2015
• Study Start: December 1, 2015
• Primary Completion: March 1, 2022
• Study Completion: August 1, 2022
• Last Updated: December 1, 2022

Record last verified: 2022-11

Locations

CH (2)