Intravitreal Adalimumab in Inherited and Degenerative Retinal Diseases

NCT ID: NCT07348588

Last Updated: 2026-01-16

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-01
• Study Completion Date: 2026-02-01

Brief Summary

This prospective, comparative pilot study investigates the safety and functional outcomes of intravitreal adalimumab (ADA) in patients with Retinitis Pigmentosa (RP) and Extensive Macular Atrophy with Pseudodrusen-like Appearance (EMAP).

Participants will receive three intravitreal injections of adalimumab (2 mg/0.05 mL) at two-month intervals (M0, M2, M4).

The primary objective is to assess functional changes after 6 months, focusing on visual-field preservation (Field Preservation Deviation Index - FPDI, Mean Deviation - MD) and best-corrected visual acuity (LogMAR).

Secondary outcomes include alterations in 30-Hz flicker ERG amplitude, OCT parameters (central macular thickness and ellipsoid zone length), and ocular safety measures such as intraocular pressure and inflammatory response.

Detailed Description

Retinitis pigmentosa (RP) represents a genetically and phenotypically heterogeneous group of inherited retinal dystrophies characterized by progressive photoreceptor degeneration, classically beginning with rod dysfunction and followed by cone loss. Patients typically present with nyctalopia, peripheral visual-field constriction, and, in advanced stages, central vision impairment. Despite significant advances in gene-specific, cell-based, and prosthetic approaches, most patients currently lack broadly applicable interventions capable of slowing or reversing disease progression across RP's wide genotypic spectrum.

Recent evidence reframes RP as not only a genetic degenerative process but also a state of chronic para-inflammation in the outer retina. Microglial activation, breakdown of the blood-retinal barrier, and overexpression of pro-inflammatory cytokines-particularly tumor necrosis factor-alpha (TNF-α)-have been implicated in accelerating photoreceptor apoptosis and secondary cone degeneration. Within this biological context, adalimumab (ADA), a fully human monoclonal antibody that selectively inhibits TNF-α, offers a mechanism-based therapeutic rationale for mitigating inflammatory injury in RP.

This prospective, single-arm pilot study was designed to evaluate the functional impact and ocular safety of intravitreal adalimumab in patients with RP. Participants received three intravitreal ADA injections (2 mg/0.05 mL) at two-month intervals (M0, M2, M4). The primary assessments included best-corrected visual acuity (BCVA, LogMAR), visual-field metrics (FPDI, MD, PSD; using 10-2 for advanced and 24-2 for less advanced disease), and 30-Hz flicker ERG when measurable. Structural endpoints comprised OCT-derived central macular thickness and ellipsoid zone (EZ) length. Outcomes were analyzed for pre-post change over six months (M0-M6) and feasibility in a real-world clinical research setting.

This exploratory study aims to generate foundational data to guide future controlled trials of anti-TNF therapy in inherited retinal degenerations with inflammatory components.

Conditions

Retinitis Pigmentosa (RP); Extensive Macular Atrophy With Pseudodrusen (EMAP)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

intravitreal injection of adalimumab

Participants receive intravitreal injections of adalimumab 2 mg/0.05 mL at baseline (M0), month 2 (M2), and month 4 (M4).

This arm evaluates the effect of anti-TNF-α immunomodulation alone on visual function and retinal structure in patients with Retinitis Pigmentosa and EMAP.

Group Type: EXPERIMENTAL

Intravitreal Adalimumab

Intervention Type: DRUG

Participants receive intravitreal injections of adalimumab 2 mg/0.05 mL at baseline (M0), month 2 (M2), and month 4 (M4).

Interventions

Intravitreal Adalimumab

Participants receive intravitreal injections of adalimumab 2 mg/0.05 mL at baseline (M0), month 2 (M2), and month 4 (M4).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Age ≥ 18 years.

• Clinical diagnosis of retinitis pigmentosa (RP) or EMAP (Extensive Macular Atrophy with Pseudodrusen-like Appearance) confirmed by multimodal evaluation.
• Best-corrected visual acuity (BCVA) ≥ counting fingers at 1 meter (approximately ≤ 1.9 logMAR) in the study eye.
• Measurable visual field on iCare COMPASS (10-2 or 24-2) with acceptable reliability indices.
• Clear ocular media adequate for safe intravitreal injection and high-quality OCT imaging.
• Ability and willingness to provide written informed consent.
• Ability to comply with scheduled study visits (Baseline [M0], Day 7-14 after injections, Month 2 [M2], Day 7-14, Month 4 [M4], Day 7-14, and Month 6 [M6]).
• For ERG subset only: presence of a recordable baseline 30-Hz flicker ERG response (signal-to-noise ratio ≥ 3:1 and amplitude ≥ 3.0 µV).
• Note: Absence of a measurable flicker ERG response does not exclude participation in the main study.

Exclusion Criteria

• Active ocular inflammation (anterior, intermediate, or posterior uveitis) or infectious ocular disease in the study eye.
• Active choroidal neovascularization or other macular diseases unrelated to RP or EMAP.
• Uncontrolled glaucoma (intraocular pressure > 21 mmHg despite therapy) or optic neuropathies not related to RP or EMAP.
• Significant media opacity that may impair imaging quality or safe intravitreal injection.
• Recent ocular interventions that may confound study outcomes, including:
• Intravitreal therapy within 3 months prior to enrollment.
• Periocular corticosteroid injection within 3 months prior to enrollment.
• Major intraocular surgery within 3 months prior to enrollment.
• Known hypersensitivity to adalimumab, povidone-iodine, local anesthetics, or any formulation components.
• Coagulopathy or contraindications to ocular injections (platelet count < 100,000/µL or INR > 1.5 unless corrected).
• Pregnancy or breastfeeding.
• Women of childbearing potential unwilling to use effective contraception during the study period.
• Uncontrolled systemic disease that increases risk or interferes with study participation or completion.
• Participation in another interventional clinical trial within 3 months prior to enrollment.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centro de Pesquisa Rubens Siqueira

OTHER

Sponsor Role: lead

Responsible Party

Rubens Camargo Siqueira

MD,PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Rubens Siqueira Research Center

São José do Rio Preto, São Paulo, Brazil

Countries

Brazil

References

Siqueira RC, Brandao CC. The Role of Cytokines in Degenerative Retinal Diseases: A Comprehensive Review. Biomedicines. 2025 Jul 15;13(7):1724. doi: 10.3390/biomedicines13071724.

Reference Type: BACKGROUND

PMID: 40722794 (View on PubMed)

Other Identifiers

ADARET

Identifier Type: -

Identifier Source: org_study_id