A Study of the Efficacy, Safety, and Pharmacokinetics of A 36-Week Refill Regimen for the Port Delivery System with Ranibizumab in Patients with Wet Age-Related Macular Degeneration (Velodrome)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Patients

Age range

65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Trial duration

22 Oct 2021 → ongoing

Decision date (initial)

2024-07-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche AG

External identifiers

EU CT number

2023-507130-24-00

EudraCT number

2020-001313-20

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Others, Pharmacokinetic

To evaluate the efficacy of ranibizumab 100 mg/mL delivered via the port delivery system with ranibizumab (PDS) every 36 weeks (Q36W) compared with every 24 weeks (Q24W) on the basis of change from baseline in best-corrected visual acuity (BCVA) score averaged over Weeks 68 and 72

Secondary objectives 4

1. Efficacy of ranibizumab 100 mg/mL delivered via PDS Q36W versus Q24W on basis of change from baseline in BCVA score over time, proportion of patients with BCVA score of 69 letters/better/ 38 letters/ worse over time, proportion of patients who prefer ranibizumab delivered via PDS compared with intravitreal treatment (IVT), proportion of patients with bilateral disease who report preferring ranibizumab delivered via PDS compared with fellow eye IVT, proportion of patients who lose <10, <5, or gain >= 0 letters in BCVA score from baseline over time, change from baseline in center point thickness (CPT), proportion of patients who do not undergo supplemental treatment with intravitreal ranibizumab, mean overall treatment satisfaction
2. Safety, tolerability of ranibizumab delivered via PDS, and device and procedure related safety
3. Pharmacokinetic profile of ranibizumab delivered via PDS Q36W compared with Q24W
4. Formation of anti-drug antibodies (ADAs) to ranibizumab delivered via PDS

Conditions and MedDRA coding

Neovascular age-related macular degeneration (nAMD)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

IPD plan description

N/A

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Ocular inclusion criteria: Initial diagnosis nAMD within 9 months prior to the screening visit
2. Ocular inclusion criteria: Previous treatment with at least three anti- vascular endothelial growth factor (VEGF) intravitreal injections for nAMD per standard of care within 6 months prior to the screening visit
3. Ocular inclusion criteria: Availability of historical visual acuity data prior to the first anti-VEGF treatment for nAMD until the time of study enrollment
4. Ocular inclusion criteria: BCVA of 34 letters or better, using Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters at screening and enrollment visits
5. Ocular inclusion criteria: With any subtype of nAMD lesions - nAMD lesions at the time of diagnosis must involve the macula (6-mm diameter centered at the fovea)
6. Ocular inclusion criteria: Sufficiently clear ocular media and adequate pupillary dilation to allow for analysis and grading by the central reading center of fundus photography, fluorescein angiography, fundus autofluorescence image, and OCT images

Exclusion criteria 6

1. Prior Ocular Treatment: Study Eye History of vitrectomy surgery, submacular surgery, or other surgical intervention for AMD
2. Prior Ocular Treatment: Either Eye Prior participation in a clinical trial involving any therapies for nAMD, within 9 months from the time of nAMD diagnosis
3. CNV Lesion Characteristics: Study Eye Subretinal hemorrhage that involves the center of the fovea, if the hemorrhage is greater than 0.5 disc area in size at screening
4. Concurrent Systemic Conditions: Uncontrolled blood pressure
5. Concurrent Systemic Conditions: Use of any systemic anti-VEGF agents
6. Concurrent Systemic Conditions: Use of antimitotic or antimetabolite therapy within 30 days or 5 elimination half-lives of the enrollment visit

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in BCVA score averaged over Weeks 68 and 72, as assessed using the ETDRS chart starting at a distance of 4 meters

Secondary endpoints 20

1. Change from baseline in BCVA score over time (up to and including Week 72)
2. Proportion of patients with BCVA score of 69 letters or better averaged over Weeks 68 and 72
3. Proportion of patients with BCVA score of 69 letters or better over time
4. Proportion of patients with BCVA score of 38 letters or worse averaged over Weeks 68 and 72
5. Proportion of patients with BCVA score of 38 letters or worse over time
6. Proportion of patients who report preferring ranibizumab 100 mg/mL delivered via the PDS compared with intravitreal treatment, as measured by the PDS PPPQ at Weeks 24, 40 and 72
7. Proportion of patients with bilateral disease who report preferring ranibizumab 100 mg/mL delivered via the PDS compared with intravitreal treatment, as measured by the PPPQ at Weeks 24, 40 and 72
8. Mean overall treatment satisfaction at Week 40, as measured by the Macular Disease Treatment Satisfaction Questionnaire (MacTSQ) total score in the Q36W arm compared with the Q24W arm
9. Proportion of patients who lose <10, <5, or gain >= 0 letters in BCVA score from baseline averaged over Weeks 68 and 72
10. Proportion of patients who lose <10, <5, or gain >= 0 letters in BCVA score from baseline over time
11. Change from baseline in CPT up to and including Week 72
12. Change from baseline in CST over time, up to and including Week 72
13. Proportion of patients who do not undergo supplemental treatment with intravitreal ranibizumab 0.5 mg before each refill-exchange procedure
14. Incidence and severity of ocular and systemic adverse events in Q36W compared with Q24W
15. Incidence, severity, and duration of adverse events of special interest, including ocular adverse events of special interest in Q36W compared with Q24W
16. Incidence, severity, and duration of ocular adverse events of special interest during the postoperative period and follow-up period in all enrolled patients
17. Incidence and severity of adverse device effects in the Q36W and Q24W arms
18. Incidence, causality, severity, and duration of anticipated serious adverse device effects in the Q36W and Q24W arms
19. Observed serum concentration of ranibizumab at specified timepoints
20. Incidence of treatment-emergent ADAs to ranibizumab during the study

Investigational products

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

Test 2

Auxiliary 1

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

Postcode

4058

Country

Switzerland

Scientific contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information Support Line - TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information Support Line - TISL

Third parties 10

Locations

6 EU/EEA countries · 62 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 121 files

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

Application history

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