RO7497372 for Diabetic Macular Edema

(Pregonda Trial)

Recruiting at 11 trial locations

Overseen By Reference Study ID Number: BP44175 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Genentech, Inc.

Must not be taking: Anti-IL-6 treatments

Disqualifiers: Active cancer, Stroke, Myocardial infarction, Uncontrolled glaucoma, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

176 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will assess the safety and tolerability of RO7497372 in participants with DME. The study consists of 2 parts. Part 1 will test multiple-ascending doses of RO7497372 after unilateral intravitreal (IVT) administration in participants with DME. The main purpose of Part 1 is to provide data for RO7497372 safety and tolerability, as well as to characterize the ocular and systemic pharmacokinetics (PK), systemic anti-drug antibodies (ADA), and duration of target engagement, i.e., the pharmacodynamics (PD) in aqueous humor (AH) and blood. Part 2 will evaluate the safety, tolerability, PK, and PD of two dose strengths of RO7497372 (low dose and high dose), identified as safe and tolerated in Part 1.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions a 'washout' period for pre-treated participants, which means you might need to stop certain treatments before starting the trial.

What data supports the effectiveness of the drug RO7497372 for Diabetic Macular Edema?

Research shows that anti-VEGF therapies, which are similar to RO7497372, have been effective in improving vision in patients with diabetic macular edema by reducing swelling in the eye. ^{1 2 3 4 5}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for individuals with Diabetic Macular Edema (DME), a condition where fluid accumulates in the retina due to diabetes. Participants should have DME in one eye and be willing to receive injections directly into the eye. Specific eligibility details are not provided, but typically include age range, disease severity, and no recent treatments that could interfere.

Inclusion Criteria

Participant consents to AH collection

I have not started treatment or have completed a treatment washout period.

I have been diagnosed with diabetes (type 1 or type 2).

Exclusion Criteria

I have not had a fever or its effects in the last week.

I haven't had cataract surgery in the last 12 weeks and don't plan any surgery during the study.

I haven't had a major illness or surgery in the last 4 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1

Participants receive multiple ascending doses of RO7497372, 3 times every 4 weeks as an IVT injection up to Week 8

8 weeks

Treatment Part 2

Participants receive 6 doses of RO7497372, either low or high dose, every 4 weeks followed by 3 doses every 8 weeks as an IVT injection up to Week 44

44 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

• RO7497372

Trial Overview The study tests RO7497372, a new medication given as an injection inside the eye (intravitreal) for treating DME. It has two parts: Part 1 determines safety and how the body processes it; Part 2 tests two different doses found safe in Part 1 for their effectiveness and side effects.

Participant Groups

Group I: Part 2: RO7497372 Low Dose Experimental Treatment 1 Intervention

Participants will receive 6 doses of RO7497372, low dose, Q4W followed by 3 doses, every eight weeks (Q8W) as an IVT injection up to Week 44 in the study eye.

Group II: Part 2: RO7497372 High Dose Experimental Treatment 1 Intervention

Participants will receive 6 doses of RO7497372, high dose, Q4W followed by 3 doses, Q8W as an IVT injection up to Week 44 in the study eye.

Group III: Part 1: Multiple Ascending Dose Experimental Treatment 1 Intervention

Participants will receive multiple ascending doses of RO7497372, 3 times every 4 weeks (Q4W) as an IVT injection up to Week 8 in the study eye.

Who Is Running the Clinical Trial?

Genentech, Inc.

Lead Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Findings from Research

In a study of 2614 eyes from 1964 patients with diabetic macular oedema, intravitreal anti-VEGF injections led to significant visual acuity improvements, with half of the patients achieving a favorable outcome of more than 70 letters on the Early Treatment Diabetic Retinopathy Study scale within 1.9 months.

However, among those who initially reached this visual acuity, 50% experienced a decline below 70 letters by 14.7 months, indicating that while anti-VEGF therapy is effective, its benefits may diminish over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An open-source data set of anti-VEGF therapy in diabetic macular oedema patients over 4 years and their visual acuity outcomes. Kern, C., Fu, DJ., Huemer, J., et al.[2022]

In a study of 28,658 treatment-naïve patients with diabetic macular edema (DMO), those who received an average of 6.4 anti-VEGF injections over one year gained a mean of +4.2 letters in visual acuity, indicating a positive but modest improvement.

Patients with moderately severe baseline visual impairment (20/70 to 20/200) who received 10 or more injections showed significant improvement (+10.3 letters), while those with better baseline vision (≥20/40) were at risk of losing visual acuity, highlighting the importance of treatment intensity and baseline condition in visual outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Visual acuity outcomes and anti-VEGF therapy intensity in diabetic macular oedema: a real-world analysis of 28 658 patient eyes. Ciulla, TA., Pollack, JS., Williams, DF.[2021]

Aflibercept should be initiated with intensive proactive dosing of 2 mg every 4 weeks, with most experts recommending six initial doses based on clinical experience, which aligns with Protocol T rather than the five doses suggested in the product guidelines.

For patients showing a good response but not yet stable, continuing with 4-weekly aflibercept is advised until stability is achieved, while those with no response may need to consider switching to other treatments, highlighting the importance of tailored approaches in managing diabetic macular oedema.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Translating evidence into practice: recommendations by a UK expert panel on the use of aflibercept in diabetic macular oedema. Pearce, I., Bailey, C., Fletcher, E., et al.[2021]

The treat-and-extend (T&E) regimen of anti-VEGF therapy for macular edema due to retinal vein occlusions showed a significant mean improvement of 15.7 ETDRS letters after 12 months, indicating effective treatment outcomes.

Central retinal thickness also improved by an average of 269.7 μm at 12 months, with relatively few adverse events reported, suggesting that T&E regimens are both effective and safe for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treat-and-extend regimens of anti-vascular endothelial growth factor therapy for retinal vein occlusions: a systematic review and meta-analysis. Nanji, K., Khan, M., Khalid, MF., et al.[2022]

In a study of 66 patients with macular oedema due to retinal vein occlusions, combination therapy (initial Ranibizumab with optional Ozurdex and laser) led to significant improvements in visual acuity over three years, with 63% of patients experiencing better vision.

The treatment also resulted in a notable reduction in the frequency of injections needed, with 39.6% of patients not requiring any injections by Year 3, indicating a long-term efficacy and safety of the combination therapy in managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination Therapy for Macular Oedema in Retinal Vein Occlusions: 3-Year Results from a Real-World Clinical Practice. Horner, F., Lip, PL., Mushtaq, B., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

An open-source data set of anti-VEGF therapy in diabetic macular oedema patients over 4 years and their visual acuity outcomes. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Visual acuity outcomes and anti-VEGF therapy intensity in diabetic macular oedema: a real-world analysis of 28 658 patient eyes. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Translating evidence into practice: recommendations by a UK expert panel on the use of aflibercept in diabetic macular oedema. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Treat-and-extend regimens of anti-vascular endothelial growth factor therapy for retinal vein occlusions: a systematic review and meta-analysis. [2022]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Combination Therapy for Macular Oedema in Retinal Vein Occlusions: 3-Year Results from a Real-World Clinical Practice. [2022]