A Study to Investigate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of RO7200220 Administered Intravitreally in Patients with Uveitic Macular Edema

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Trial duration

21 Apr 2023 → 9 Jul 2025

Decision date (initial)

2023-04-14

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche AG

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Pharmacokinetic, Efficacy, Safety

To evaluate the efficacy of RO7200220 on best corrected visual acuity (BCVA) functional outcome compared with sham

Secondary objectives 10

1. To evaluate the efficacy of RO7200220 on BCVA functional outcome compared with sham, at Week 20 (8 weeks after the final study drug dose)
2. To evaluate the efficacy of RO7200220 on the mean BCVA functional outcomes compared with sham
3. To evaluate the efficacy of RO7200220 on the mean anatomical (change in central subfield thickness (CST)) outcomes compared with sham
4. To evaluate the safety of RO7200220 compared with sham
5. To evaluate the safety of RO7200220 in study eye compared with fellow eye
6. To characterize pharmacokinetics of RO7200220
7. To characterize the aqueous humor pharmacodynamics (IL‑6)
8. To investigate the formation of serum ADAs
9. To evaluate potential effects of serum ADAs
10. To evaluate the efficacy of RO7200220 on additional functional, anatomical, and participant‑reported outcomes compared with sham

Conditions and MedDRA coding

Uveitic Macular Edema

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-003215-PIP01-22

Plan to share IPD

No

IPD plan description

N/A

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Diagnosis of macular edema associated with non‑infectious uveitis (NIU) defined as macular thickening by spectral‑domain optical coherence tomography (SD‑OCT) involving the center of the macula confirmed by central reading center with CST >/=325 μm with Spectralis (>/=315 μm with Cirrus or Topcon) at screening.
2. Diagnosis of active or inactive, acute, or chronic NIU of any etiology and of any anatomical type (anterior, intermediate, posterior, panuveitis) based on investigator assessment
3. Best corrected visual acuity (BCVA) letter score of 73 to 19 letters (both inclusive) on Early Treatment Diabetic Retinopathy Study (ETDRS)‑like charts (20/40 – 20/400 Snellen equivalent) on Day 1 based on the assessment at study site

Exclusion criteria 10

1. Evidence of active or latent tuberculosis infection and/or positive tuberculosis assay, syphilis infection, or previous or current HIV diagnosis, based on investigator’s assessment of clinical laboratory tests or physical examination
2. Serious acute or chronic medical (e.g., malignancy, metabolic dysfunction, renal failure, uncontrolled hypertension, etc.) or psychiatric illness or abnormality in clinical laboratory tests or physical examination that would preclude participation in the study
3. History of major non‑ocular surgical procedures within 1 month prior to Day 1.
4. Uncontrolled IOP or glaucoma or chronic hypotony
5. Any anatomical changes or media opacity in the study eye preventing evaluation of retina, vitreous, and capture of study images as assessed by the investigator
6. Prior use of IVT anti-VEGFs and any other IVT biologics within 2 and -4 months prior to Day 1 respectively; received IVT Methotrexate within 4 months prior to Day 1.
7. Prior macular laser therapy, cataract surgery within 6 months and laser capsulotomy within 3 months of Day 1
8. Any topical ocular corticosteroid/NSAIDs > 3 drops per day in the 14 days prior to Day 1 (D1);intraocular or periocular corticosteroid injections in the 2 months prior to D1; subconjunctival corticosteroid injection within 1 month prior to Day 1; an OZURDEX implant within 4 months prior to D1; YUTIQ, RETISERT or ILUVIEN implant within 3 years prior to D1
9. Diagnosis of macular edema due to any cause other than NIU as assessed by the investigator
10. Any major ocular conditions that may require medical or surgical intervention during the study period to prevent vision loss or likely contribute to worsening vision over the study period or preclude any visual improvement due to established structural damage or difficulty interpretation of the study results

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. Proportion of participants with ≥15 letter improvement from baseline in BCVA at Week 16

Secondary endpoints 19

1. 1. Proportion of participants with ≥15 letter improvement from baseline in BCVA at Week 20 (8 weeks after the final fixed-interval study drug dose at Week 12)
2. 2. Change from baseline in BCVA score at Week 16
3. 3. Change from baseline in central subfield thickness (CST) at Week 16
4. 4. Change from baseline in BCVA at Weeks 20 and 52
5. 5. Change from baseline in CST at Weeks 20 and 52
6. 6. Proportion of participants with UME resolution from baseline at Weeks 16 and 52
7. 7. Proportion of participants with ≥15 letter improvement from baseline in BCVA at Week 52
8. 8. 12. Change from baseline in the National Eye Institute Visual Function Questionnaire‑25 (NEI VFQ‑25) composite score at Weeks 16 and 52
9. 9. Incidence and severity of ocular adverse events, non-ocular adverse events, adverse events of special interest and selected adverse events
10. 10. AH concentration of RO7200220 (pharmacokinetics) over time
11. 11. Serum concentration of RO7200220 (pharmacokinetics) over time
12. 12. Incidence and titer of ADAs to RO7200220 during the study relative to the prevalence of ADAs at baseline
13. 13. Time to rescue treatment and number and type of rescue treatments received
14. 14. Proportion of participants without ≥15 letter loss from baseline in BCVA at Weeks 16 and 52
15. 15. Number of pro re nata PRN injections received
16. 16. Time to first PRN injection
17. 17. Percent change from baseline in corneal endothelial cell density at Week 24 and Week 52
18. 18. Relationship between ADA status and efficacy, safety, ocular PK, PD endpoints
19. 19. IL‑6 suppression in AH

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

F. Hoffmann-La Roche AG

Sponsor organisation

F. Hoffmann-La Roche AG

Address

Grenzacherstrasse 124

City

Basel Town

Postcode

4058

Country

Switzerland

Scientific contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Third parties 9

Locations

5 EU/EEA countries · 17 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 1 · Art. 52 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 29 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

10 submissions — initial application plus substantial / non-substantial modifications