ADX-038 for Geographic atrophy secondary to age-related macular degeneration

Stratification factors

• EZ/RPE loss ratio ≥1.62 (yes/no)
• Involvement of the foveal center (yes/no)

Inclusion criteria

• {"criterion_text":"- General: Age ≥60 years and ≤100 years at the time of signing informed consent.\n- General: The following vaccine requirements need to be completed at least 2 weeks prior to Day 1: a) Completed vaccination schedule for Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis serotypes (MenACWY) with appropriate boosters per local guidance; b) Completed at least 2 doses of a 3-dose vaccine series for Neisseria meningitidis serotype B (MenB). The third dose must be administered during the study but may occur after Day 1.\n- General: Participants agree to receive vaccine boosters for MenACWY, MenB, Streptococcus pneumoniae, and Haemophilus influenzae as appropriate per local guidance during the study.\n- General: Fertile men must agree to use acceptable contraceptive methods if engaged in sexual activity with a partner of childbearing potential from the time of signing the ICF until the EOS Visit or 3 months after the last dose of study drug, whichever is longer.\n- General: Fertile men must agree not to donate sperm after study drug administration on Day 1 until the EOS Visit or 3 months after the last dose of study drug, whichever is longer.\n- General: Women of childbearing potential (WOCBP) are defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception. WOCBP must have a negative serum pregnancy test during Screening and a negative urine pregnancy test on Day 1 before study drug administration and must agree to use highly effective contraceptive methods if engaged in sexual activity of childbearing potential from the time of signing the informed consent form (ICF) until the EOS Visit or 3 months after the last dose of study drug, whichever is longer. Women are considered not of childbearing potential if they are permanently sterile or if they have had no menses for 12 months without an alternative medical cause.\n- General: Women must not be breastfeeding.\n- General: Has provided written informed consent and any authorizations required by local law and is willing to comply with all study requirements for the duration of the study.\n- Study Eye: Has a clinical diagnosis of GA of macula secondary to AMD as determined by the Investigator.\n- Study Eye: Has a GA lesion that meets all following criteria during the Screening period, as determined by the CRC’s assessment of FAF imaging: a) GA lesions ≥2.5 and ≤12.5 mm2; b) If GA is multifocal, at least one focal lesion must be ≥1.25 mm2 (0.5 disc area), with the overall aggregate area of GA as specified in inclusion a; c) At least 1 GA lesion must be at least in part within a 1.5 mm radius ring centered on the fovea; d) The entire GA lesion must be completely visualized on the macula centered image and must be able to be imaged in its entirety and not contiguous with any area of peripapillary atrophy; e) Presence of any pattern of hyper autofluorescence (AF) in the junctional zone of GA (lack of hyper AF is exclusionary); f) Lesions involving the foveal center as determined by the CRC are permitted but the maximum number of participants enrolled with lesions involving the foveal center will be limited to approximately 72.\n- Study Eye: Has a GA lesion that meets all following criteria as determined by the CRC’s assessment of OCT imaging during the Screening period and just prior to Day 1 dosing: a) EZ/RPE ratio ≥ 1.19; b) RPE loss must be within the entirety of the 6 × 6 mm OCT imaging frame; c) EZ loss must be contained within the entirety of the 6 × 6 mm OCT imaging frame; d) Lesions of EZ loss which contain areas of RPE loss within its borders must not be within 0.5 mm of any border of the 6 × 6 mm OCT imaging frame. NOTE: If the initial imaging takes place >30 days prior to Day 1, the OCT image must be repeated within Day -30 to Day -7 window. Ensure timeliness (e.g., at least 7 days prior to Day 1) so that the CRCs results are received and reviewed by the Investigator prior to Day 1 dosing.\n- Study Eye: Has a BCVA of ≥24 letters using the ETDRS chart at both Screening and Day 1. If a participant has a lesion involving the center point of the fovea as determined by the CRC, participant must have a BCVA of ≥50 letters using the ETDRS chart at both Screening and Day 1.\n- Study Eye: Has adequate clarity of ocular media and adequate pupillary dilation, and fixation to permit the collection of good quality images, as determined by the Investigator."}

Exclusion criteria

• {"criterion_text":"- Has GA secondary to causes other than AMD, such as Stargardt disease, cone rod dystrophy, or toxic maculopathies like drug-induced plaquenil maculopathy in either eye.\n- Active systemic viral (including COVID-19), bacterial, or fungal infection must have a full recovery for at least 14 days prior to Day 1 in order to participate.\n- Had intraocular surgery (including lens replacement surgery) within 3 months prior to Day 1.\n- Has history of surgical repair for retinal detachment. History of laser surgery for retinal tears is allowed.\n- Has aphakia or the absence of the posterior capsule. (Note: YAG laser posterior capsulotomy for posterior capsule opacification performed ≥60 days prior to Screening is permitted.)\n- Has any ocular condition other than GA secondary to AMD that may require surgery or medical intervention during the study or, in the opinion of the Investigator, could compromise visual function during the study.\n- Has pathologic myopia as defined as spherical equivalent of the refractive error demonstrating >8 diopters of myopia or evidence of myopic maculopathy as determined by the CRC.\n- Has an active malignancy and/or history of malignancy in the past 5 years prior to Day 1, with the exception of completely excised non-melanoma skin cancer or low grade cervical intraepithelial neoplasia and with no evidence of recurrence for ≥3 years prior to Day 1.\n- Received prior treatment with any genome-altering therapy for GA, including gene therapy and gene editing.\n- Has a history or current use of non-genome-altering IVT therapy of any kind for any indication, including IVT complement inhibitors (approved or investigational), within 6 months to randomization in study eye. Prior or concurrent use of IVT in the fellow eye is allowed.\n- Has known HIV infection (per participant history and/or medical records) or positive HIV test during Screening.\n- Has known or suspected hereditary or acquired complement deficiency.\n- Has a positive serology test for hepatitis B surface antigen (HBsAg) or positive serology test for hepatitis C virus (HCV) with a detectable RNA concentration during Screening.\n- Has liver injury as indicated by any of the following abnormal liver function tests during screening; tests should be repeated if there is a significant clinical change during Screening: a) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >1.5 × upper limit of normal (ULN); b) Total bilirubin >1.5 × ULN (unless due to Gilbert’s syndrome).\n- Has any of the following laboratory parameters during Screening, tests should be repeated if there is a significant clinical change during Screening: a) White blood cell count >1.2 × ULN or <0.8 × lower limit of normal; b) Hemoglobin <9 g/dL; c) Platelet count <80,000/μL\n- Received prior or concurrent treatment with any systemic complement inhibitors within 6 months to randomization.\n- Participated in an interventional drug study within the last 90 days or 5 half-lives, whichever is longer, prior to Screening.\n- Is receiving concomitant treatment with any ocular or systemic medication that is known to be toxic to the retina at the time of Screening (e.g., hydroxychloroquine, intraocular moxifloxacin, tamoxifen). Note: Participants taking oral supplements specifically for GA/AMD (e.g., vitamin C, vitamin E, β-carotene, lutein/zeaxanthin) must be on a stable dose for at least 3 months prior to Day 1.\n- Is receiving systemic or IVT /topical (i.e., applied to eye) corticosteroids or immunosuppressive agents at the time of Screening. Agents include, but are not limited to, cyclosporine, tacrolimus, mycophenolate or mycophenolic acid, cyclophosphamide, methotrexate, cyclophosphamide, or intravenous immunoglobulins. Inhaled, intranasal, and topical (applied to skin) corticosteroids are permitted.\n- Donated any blood products (>200 mL) within 30 days prior to Screening.\n- Received a blood transfusion within 90 days prior to Screening.\n- Has any other significant medical conditions that, in the opinion of the Investigator, would make the participant unsuitable for inclusion in the study, or could interfere with study assessments or put the participant at risk for experiencing significant adverse effects during the study.\n- Has a history of recurrent invasive infections caused by encapsulated bacteria (e.g., meningococcus or pneumococcus).\n- Has a major concurrent comorbidity, including but not limited to severe kidney disease (e.g., estimated glomerular filtration rate <30 mL/min/1.73 m2, dialysis), advanced cardiac disease (e.g., New York Heart Association class IV), or severe pulmonary disease (e.g., severe pulmonary hypertension [World Health Organization class IV]). Any major cardiovascular event in the past year prior to Day 1, including a myocardial infarction or a cerebrovascular event requiring hospitalization, is also exclusionary.\n- Has a history of thermal laser therapy in the macular region.\n- Has a history of splenectomy.\n- Has a history of active tuberculosis (TB [treated or untreated]), untreated latent TB infection, or evidence of active TB during Screening (preferred testing is by QuantiFERON-TB Gold Plus test when available and per local regulations). Note: Participants with history of treated latent TB are permitted to enroll if they have evidence of completion of treatment and they meet all other eligibility criteria."}

Primary endpoints

• {"endpoint_text":"- Slope of change in GA area (square root transformation) as measured by FAF from baseline to Month 12 (expressed in mm/year) in the study eye","definition_or_measurement_approach":"Measured by fundus autofluorescence (FAF); GA area is square-root transformed; slope of change from baseline to Month 12 expressed in mm/year in the study eye."}

Secondary endpoints

• {"endpoint_text":"- Slope of change in GA area (square root transformation) as measured by FAF from baseline to Month 24 (expressed in mm/year) in the study eye; Rate of change in the macular area of photoreceptor loss (defined as an EZ-RPE thickness of 0 μm) assessed by OCT and EZ mapping at Month 12 and Month 24","definition_or_measurement_approach":"Measured by FAF for GA area (square-root transformation) from baseline to Month 24; photoreceptor loss assessed by OCT and EZ mapping (EZ-RPE thickness = 0 μm) at Month 12 and Month 24."}
• {"endpoint_text":"- Proportion of participants with ≥15 letter loss in ETDRS letters in the study eye at 2 consecutive visits or EOS Visit","definition_or_measurement_approach":"Best corrected visual acuity measured using ETDRS chart; proportion defined as participants with loss ≥15 ETDRS letters confirmed at two consecutive visits or at End Of Study visit."}

Methods

• Patient participation GP letters: country-specific 'Patient participation GP letter' documents exist for IT, PT, ES, DE indicating recruitment via General Practitioners to inform potential participants.
• Site-based recruitment at participating ophthalmology hospitals/clinics listed as trial sites in Germany, Italy, Portugal and Spain.
• Country-specific recruitment arrangements documents submitted (K1_Recruitment arrangements) for Germany, Italy, Portugal, Spain (documents present in registry).

Germany

Earliest CTIS Part Ii Submission Date

13-02-2026

Latest Decision Or Authorization Date

18-03-2026

Processing Time Days

33

Number Of Sites

8

Number Of Participants

22

Italy

Earliest CTIS Part Ii Submission Date

20-03-2026

Latest Decision Or Authorization Date

27-03-2026

Processing Time Days

7

Number Of Sites

6

Number Of Participants

22

Portugal

Earliest CTIS Part Ii Submission Date

20-01-2026

Latest Decision Or Authorization Date

17-03-2026

Processing Time Days

56

Number Of Sites

4

Number Of Participants

10

Spain

Earliest CTIS Part Ii Submission Date

20-03-2026

Latest Decision Or Authorization Date

26-03-2026

Processing Time Days

6

Number Of Sites

7

Number Of Participants

22

Primary sponsor

Full Name

Adarx Pharmaceuticals Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Cmic Inc.

Responsibilities

Operational/CRO responsibilities (sponsorDuties code: 4)

Name

Infocus Clinical Research LLC

Responsibilities

Multiple operational responsibilities including monitoring, clinical operations, data management (sponsorDuties codes: 1,10,12,13,2,5,6,9)

Name

Acm Global Central Laboratory Limited

Responsibilities

Central laboratory services (sponsorDuties code: 4)

Third parties

• {"country":"Ireland","full_name":"Insidereg Limited","duties_or_roles":"sponsorDuties codes: 12; 15 (Applicant)","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Acm Global Central Laboratory Limited","duties_or_roles":"sponsorDuties code: 4 (laboratory services)","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Keystone Bioanalytical Inc.","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Cmic Inc.","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"Slovakia","full_name":"SanaClis s.r.o.","duties_or_roles":"sponsorDuties code: 15 (Vaccine procurement)","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"MyData-TRUST","duties_or_roles":"sponsorDuties code: 15 (Data Protection Officer)","organisation_type":"Industry"}
• {"country":"United States","full_name":"Exsera BioLabs","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Educational Institution"}
• {"country":"United States","full_name":"Infocus Clinical Research LLC","duties_or_roles":"sponsorDuties codes: 1, 10, 12, 13, 2, 5, 6, 9 (multiple operational responsibilities listed)","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Portugal","full_name":"Association For Innovation And Biomedical Research On Light And Image","duties_or_roles":"sponsorDuties codes: 1, 12, 5, 8","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Austria","full_name":"RetInSight","duties_or_roles":"sponsorDuties code: 15 (Medical image analysis/review)","organisation_type":"Educational Institution"}
• {"country":"United States","full_name":"Duke Reading Center","duties_or_roles":"sponsorDuties code: 15 (Medical image analysis/review)","organisation_type":"Industry"}