Diabetic Macular EdemaPhase 2NCT05930561
4D-150 in Patients With Diabetic Macular Edema
A Phase 2 study testing 4D-150 IVT and Aflibercept IVT in people with Diabetic Macular Edema and Diabetic Retinopathy, run by 4D Molecular Therapeutics at 6 sites in 2 countries.
Trial summary
Phase 2 randomized, active-controlled, double-masked, dose-ranging trial in adults with Diabetic Macular Edema (DME). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetic Macular Edema, Diabetic Retinopathy
- What is being tested?
- 4D-150 IVT and Aflibercept IVT
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 6 sitesin 2 countries
- Study dates
- 9 Aug 2023to 28 Feb 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥18 years of age
- Type I or Type II diabetes mellitus with macular thickening secondary to DME involving the center of the fovea; diagnosis of DME must be within 2 years of Screening
- CST ≥ 350 μm (Spectralis SD-OCT) in the study eye at Screening, confirmed by the independent reading center
- Demonstrate clinical response to on-study aflibercept injection in the study eye.
- Decreased visual acuity attributable primarily to DME
- BCVA in the study eye between 25 and 83 ETDRS letters, inclusive (~20/320 and 20/25, respectively) at Screening
Show all 9Show fewer
- Study eye amenable to IVT injection
- Sufficient clear ocular media, pupil dilation and fixation in the study eye to permit adequate imaging; ability to perform tests of visual and retinal function and structure; and ability to comply with other protocol-specified procedures
- Provide written informed consent
Who cannot join
- Macular edema in the study eye considered to be secondary to a cause other than DME
- Systemic anti-VEGF treatment (e.g. sunitinib, bevacizumab, pazopanib) within 6 months, or anticipated need for systemic anti-VEGF therapy during study participation
- Systemic corticosteroids (oral, intravenous, intramuscular, intra-articular) or other immunosuppressive medications within 3 months
- Received an investigational drug, agent, device, or therapy (ocular or non-ocular) in the 3 months (or at least 5 half-lives, whichever is longer) prior to 4D-150 administration (Day 1)
- Prior gene therapy (ocular or non-ocular) and/or ocular stem cell therapy in either eye
- Any concurrent ocular condition in the study eye that is likely to require surgical intervention (e.g. cataract surgery) during the 2 year (104 week) study duration
- Note: Other inclusion/exclusion criteria apply.
Trial locations and contacts
6 sites in 2 countries.
6 sites in 2 countries
United States5 sites
Austin Clinical Research
Austin, Texas, 78750
Erie Retina Research
Erie, Pennsylvania, 16507
Verum Research, LLC
Eugene, Oregon, 97401
Cumberland Valley Retina Consultants
Hagerstown, Maryland, 21740
Piedmont Eye Center
Lynchburg, Virginia, 24502
Puerto Rico1 site
Emanuelli Research and Development Center
Arecibo, Puerto Rico, X00612
About this study
Official title: A Phase 2 Randomized, Active-Controlled, Double-masked Trial of Intravitreal 4D-150 Gene Therapy in Adults With Diabetic Macular Edema (SPECTRA)
Phase 2 randomized, active-controlled, double-masked, dose-ranging trial in adults with Diabetic Macular Edema (DME).
Read the detailed description
This Phase 2 trial is a prospective, multicenter, randomized, active-controlled, double-masked dose-ranging trial to evaluate the safety and efficacy of 4D-150 in adults with DME. The trial will be conducted in two parts: Dose Confirmation and Dose Expansion.
- Conditions
- Diabetic Macular Edema, Diabetic Retinopathy
- Being tested
- 4D-150 IVT, Aflibercept IVT
- Keywords
- Retinal gene therapy, Intravitreal gene therapy, DME, SPECTRA
- Medical subject headings
- Diabetic Retinopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
4D-150 IVTBiological
4D-150: AAV-based gene therapy comprised of miRNA targeting VEGF-C and codon-optimized sequence encoding aflibercept.
Aflibercept IVTBiological
Also called Eylea
Commercially available Active Comparator
| Study group | Role | What they receive |
|---|---|---|
| 4D-150 Part 1 Dose Confirmation Dose Level 1 | Experimental | 4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1. Receives: Biological: 4D-150 IVT |
| 4D-150 Part 1 Dose Confirmation Dose Level 2 | Experimental | 4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1. Receives: Biological: 4D-150 IVT |
| 4D-150 Part 2 Dose Expansion Dose Level 1 | Experimental | 4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1. Receives: Biological: 4D-150 IVT |
| 4D-150 Part 2 Dose Expansion Dose Level 2 | Experimental | 4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1. Receives: Biological: 4D-150 IVT |
| 4D-150 Part 2 Dose Expansion Control | Active comparator | Aflibercept at a fixed regimen will be administered. Receives: Biological: Aflibercept IVT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and severity of TEAEs and SAEs, including clinically significant changes in safety parameters (Part 1)
Measured: 60 months
Annualized number of aflibercept injections in the study eye (Part 2)
Measured: 52 weeks
Secondary outcomes (3)
Mean cumulative number of aflibercept injections over time
Measured: 52 weeks
Change from baseline in BCVA as assessed using the ETDRS Visual Acuity Chart at Weeks 52 and 104
Measured: 104 weeks
Change from baseline in CST measured by spectral domain optical coherence tomography (SD-OCT) at Weeks 104
Measured: 104 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jul 2023
- Study start9 Aug 2023
- Primary completion28 Feb 2029 (estimated)
- Study completion28 Feb 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetic Macular EdemaStudies of the same condition, open and under way.
- More trials run by 4D Molecular TherapeuticsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- In Dose Confirmation (Part 1), subjects (n=12-18) will be sequentially assigned to one of two open-label dose levels of 4D-150 (n=6-9 per dose level). In Dose Expansion (Part 2), subjects (n=54) will be randomized to receive one of two dose levels of 4D-150 (n=18 per dose level) based on results from Dose Confirmation, or aflibercept control (n=18). Subjects will be masked to treatment arm in Dose Expansion (Part 2).
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 72 participants (estimated)
Sponsor and investigators
- Lead sponsor
- 4D Molecular Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Julie Clark, MD, Study director, 4D Molecular Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05930561
- Sponsor's protocol ID
- 4D-150-C002
- Status last verified
- Aug 2026
- First submitted
- 26 Jun 2023
- Last updated
- 21 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Calton MA, Croze RH, Burns C, Beliakoff G, Vazin T, Szymanski P, Schmitt C, Klein A, Leong M, Quezada M, Holt J, Bolender G, Barglow K, Khoday D, Mason T, Delaria K, Hassanipour M, Kotterman M, Khanani AM, Schaffer D, Francis P, Kirn D. Design and Characterization of a Novel Intravitreal Dual-Transgene Genetic Medicine for Neovascular Retinopathies. Invest Ophthalmol Vis Sci. 2024 Dec 2;65(14):1. doi: 10.1167/iovs.65.14.1.
PubMed 39620832
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Randomized, Active-Controlled, Double-masked Trial of Intravitreal 4D-150 Gene Therapy in Adults With Diabetic Macular Edema (SPECTRA)
- ClinicalTrials.gov ID
- NCT05930561
- Acronym / sponsor ID
- 4D-150-C002
- Conditions
- Diabetic Macular Edema, Diabetic Retinopathy
- Keywords
- Retinal gene therapy, Intravitreal gene therapy, DME, SPECTRA
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 72 participants (estimated)
- Lead sponsor
- 4D Molecular TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 9 Aug 2023 (actual)
- Primary completion
- 28 Feb 2029 (estimated)
- Study completion
- 28 Feb 2029 (estimated)
- First posted
- 5 Jul 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Phase 2 randomized, active-controlled, double-masked, dose-ranging trial in adults with Diabetic Macular Edema (DME).
Detailed description
This Phase 2 trial is a prospective, multicenter, randomized, active-controlled, double-masked dose-ranging trial to evaluate the safety and efficacy of 4D-150 in adults with DME. The trial will be conducted in two parts: Dose Confirmation and Dose Expansion.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 5
- Model description
- In Dose Confirmation (Part 1), subjects (n=12-18) will be sequentially assigned to one of two open-label dose levels of 4D-150 (n=6-9 per dose level). In Dose Expansion (Part 2), subjects (n=54) will be randomized to receive one of two dose levels of 4D-150 (n=18 per dose level) based on results from Dose Confirmation, or aflibercept control (n=18). Subjects will be masked to treatment arm in Dose Expansion (Part 2).
| Arm | Type | Receives |
|---|---|---|
| 4D-150 Part 1 Dose Confirmation Dose Level 1 | Experimental | Biological: 4D-150 IVT4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1. |
| 4D-150 Part 1 Dose Confirmation Dose Level 2 | Experimental | Biological: 4D-150 IVT4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1. |
| 4D-150 Part 2 Dose Expansion Dose Level 1 | Experimental | Biological: 4D-150 IVT4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1. |
| 4D-150 Part 2 Dose Expansion Dose Level 2 | Experimental | Biological: 4D-150 IVT4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1. |
| 4D-150 Part 2 Dose Expansion Control | Active comparator | Biological: Aflibercept IVTAflibercept at a fixed regimen will be administered. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- ≥18 years of age
- Type I or Type II diabetes mellitus with macular thickening secondary to DME involving the center of the fovea; diagnosis of DME must be within 2 years of Screening
- CST ≥ 350 μm (Spectralis SD-OCT) in the study eye at Screening, confirmed by the independent reading center
- Demonstrate clinical response to on-study aflibercept injection in the study eye.
- Decreased visual acuity attributable primarily to DME
Key exclusion criteria (7 listed)
- Macular edema in the study eye considered to be secondary to a cause other than DME
- Systemic anti-VEGF treatment (e.g. sunitinib, bevacizumab, pazopanib) within 6 months, or anticipated need for systemic anti-VEGF therapy during study participation
- Systemic corticosteroids (oral, intravenous, intramuscular, intra-articular) or other immunosuppressive medications within 3 months
- Received an investigational drug, agent, device, or therapy (ocular or non-ocular) in the 3 months (or at least 5 half-lives, whichever is longer) prior to 4D-150 administration (Day 1)
- Prior gene therapy (ocular or non-ocular) and/or ocular stem cell therapy in either eye
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 4D-150 IVT4D-150: AAV-based gene therapy comprised of miRNA targeting VEGF-C and codon-optimized sequence encoding aflibercept. | Biological | 4D-150 Part 1 Dose Confirmation Dose Level 1, 4D-150 Part 1 Dose Confirmation Dose Level 2, 4D-150 Part 2 Dose Expansion Dose Level 1, 4D-150 Part 2 Dose Expansion Dose Level 2 |
| Aflibercept IVTAlso: EyleaCommercially available Active Comparator | Biological | 4D-150 Part 2 Dose Expansion Control |
Primary outcome
Incidence and severity of TEAEs and SAEs, including clinically significant changes in safety parameters (Part 1)
Time frame: 60 months
Annualized number of aflibercept injections in the study eye (Part 2)
Time frame: 52 weeks
3 secondary outcomes
Mean cumulative number of aflibercept injections over time
Time frame: 52 weeks
Change from baseline in BCVA as assessed using the ETDRS Visual Acuity Chart at Weeks 52 and 104
Time frame: 104 weeks
Change from baseline in CST measured by spectral domain optical coherence tomography (SD-OCT) at Weeks 104
Time frame: 104 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2026.
- Derived from this study: PubMed 39620832Calton MA, Croze RH, Burns C, Beliakoff G, Vazin T, Szymanski P, Schmitt C, Klein A, Leong M, Quezada M, Holt J, Bolender G, Barglow K, Khoday D, Mason T, Delaria K, Hassanipour M, Kotterman M, Khanani AM, Schaffer D, Francis P, Kirn D. Design and Characterization of a Novel Intravitreal Dual-Transgene Genetic Medicine for Neovascular Retinopathies. Invest Ophthalmol Vis Sci. 2024 Dec 2;65(14):1. doi: 10.1167/iovs.65.14.1.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Julie Clark, MD study director
4D Molecular Therapeutics
6 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 4D-150 IVT and Aflibercept IVT in people with Diabetic Macular Edema and Diabetic Retinopathy, run by 4D Molecular Therapeutics at 6 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 21 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence and severity of TEAEs and SAEs, including clinically significant changes in safety parameters (Part 1) (time frame: 60 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05930561, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2026.