The purpose of this study is to confirm how well aflibercept works in babies with ROP, comparing it with laser therapy. The study also has the objective to demonstrate how safe aflibercept is when used in babies. We will also learn how the drug…
ID
Source
Brief title
Condition
- Retina, choroid and vitreous haemorrhages and vascular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Proportion of patients with absence of active ROP and unfavorable structural
outcomes at 24 weeks after starting study treatment.
Secondary outcome
- Number of requirement for intervention with a second treatment modality from
baseline to week 24
- Recurrence of ROP from baseline to week 24
- To explore new ROP Activity Scale proposed by the International Neonatal
Consortium from baseline to week 24
- Number of aflibercept administrations from baseline to week 24.
- Number of laser treatments from baseline to Week 24.
- Proportion of participants with ocular TEAEs and SAEs from baseline to week
24.
- Proportion of participants with systemic TEAEs and SAEs from baseline to week
24.
- Systemic exposure to free aflibercept (at expected maximum plasma
concentration and during elimination period from plasma) determined by sparse
sampling from baseline to week 24.
- Presence of anti-drug antibodies before and 12 weeks after aflibercept
injection.
Background summary
Retinopathy of prematurity is a proliferative vascular retinopathy caused by an
abnormal development of the vascularization of the peripheral retina in
premature infants. It affects mainly newborns with a preterm gestational age (*
32 weeks) and very low birth weight (* 1500 g). ROP remains a major cause of
childhood blindness globally. As ROP is characterized by incomplete
vascularization of the retina in premature infants, it has also been associated
with increased levels of VEGF. Upregulation of VEGF due to ischemia in the
avascular retina may induce pathologic neovascularization and subsequently lead
to retinal detachment and blindness, as seen in late stage ROP. Aflibercept
inhibits these effects of VEGF. Based on the drug*s mode of action, aflibercept
has a high potential to become an effective treatment option for the treatment
of ROP.
Study objective
The purpose of this study is to confirm how well aflibercept works in babies
with ROP, comparing it with laser therapy. The study also has the objective to
demonstrate how safe aflibercept is when used in babies. We will also learn how
the drug moves into, through and out of the body.
Study design
This is a phase 3, multicenter, randomized, 2-arm, open-label clinical study to
assess the efficacy, safety, and tolerability of IVT aflibercept versus laser
photocoagulation in subjects with ROP. The study consists of screening/baseline
(1 or 2 visits), a 23-week treatment period (including retreatment and rescue
treatment), and a final visit at Week 24 (up to Week 27 for subjects treated
after Week 21).
Intervention
- Subjects randomized to aflibercept will receive a single intravitreal (IVT)
injection of aflibercept 0.4 mg/0.01 mL per eligible eye at baseline.
- Subjects randomized to laser photocoagulation will undergo treatment in each
eligible eye at baseline. Laser ablation should be as complete as possible as
judged by the investigator.
Study burden and risks
Treatment with lasertherapy and/or aflibercept may have some therapeutic
benefit but this cannot be guaranteed. Please refer to section E9 for a
detailed description of the risks associated with participation.
Participation in the study involves approximately 14 visits in a time period of
24 weeks with physical exams, bloodsampling and eye examinations as described
in the protocol. Examinations including eye examinations and physical exams,
will be performed at specific visits as described in the protocol and the
patient information and informed consent forms.
Energieweg 1
Mijdrecht 3641RT
NL
Energieweg 1
Mijdrecht 3641RT
NL
Listed location countries
Age
Inclusion criteria
1.Gestational age at birth * 32 weeks or birth weight * 1500 g, Type of
Participant and Disease Characteristics, 2.Subjects with treatment-naïve ROP
classified according to the International Classification for ROP in at least
one eye as:, - Zone I Stage 1 plus, or 2 plus, or 3 non-plus or 3 plus, or Zone
II Stage 2 plus or 3 plus, or AP-ROP, 3.Weight at baseline (day of treatment) *
800 g, 4.Male or female, 5.Signed informed consent from parent(s)/legally
authorized representative(s) as described in Section 10.1.3 of the clinical
trial protocol, which includes compliance with the requirements and
restrictions listed in the informed consent form (ICF) and in the clinical
trial protocol
Exclusion criteria
Subjects are excluded from the study if any of the following *per subject*
criteria are met. A potential study eye is excluded from the study if any of
the *per eye* criteria are met:, Medical Conditions * per subject, 1.Known or
suspected chromosomal abnormality, genetic disorder or syndrome, 2.Previous
exposure to any IVT or systemic anti-VEGF agent, including maternal exposure
during pregnancy and/or during breastfeeding, 3.Clinically significant
neurological disease (eg, intraventricular hemorrhage grade 3 or higher,
periventricular leukomalacia, congenital brain lesions significantly impairing
optic nerve function, severe hydrocephalus with significantly increased
intracranial pressure), 4.Pediatric conditions rendering the infant ineligible
for study intervention at baseline or for repeated blood draws as evaluated by
a NICU specialist and a study ophthalmologist, 5.Presence of active ocular
infection within 5 days of the first treatment, Medical Conditions * per eye,
6.Advanced stages of ROP with partial or complete retinal detachment (ROP
Stages 4 and 5), 7.ROP involving only Zone III , 8.Ocular abnormalities that
may interfere with the administration of study intervention or assessment of
the study primary endpoint , Prior/Concomitant Therapy * per subject,
9.Postnatal treatment with oral or intravenous corticosteroids at an equivalent
dose of prednisone * 1 mg/kg/day for >2 weeks within 14 days of the first study
intervention, Prior/Concomitant Therapy * per eye, 10.Previous surgical or
nonsurgical treatment for ROP (IVT anti-VEGF injection, ablative laser therapy,
cryotherapy, and vitrectomy) , Prior/Concurrent Clinical Study Experience,
11.Participation of the subject or the mother in other clinical trials
requiring administration of investigational treatments (other than vitamins and
minerals) at the time of screening, or within 30 days or 5 half-lives of
administration of the previous study drug, whichever is longer.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2018-002611-99-NL |
| CCMO | NL69813.056.19 |