Clinical Trial Results:
An Exploratory, Prospective, Multi-Center, Open-Label, Single-Arm, Interventional, Phase IIB Study to Investigate Aqueous Humor and Multimodal Imaging Biomarkers in Treatment-Naïve Patients With Diabetic Macular Edema Treated With Faricimab (RO6867461) - ALTIMETER STUDY
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Summary
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EudraCT number |
2020-001174-30 |
Trial protocol |
DE PL IT HR |
Global end of trial date |
22 Dec 2022
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Results information
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Results version number |
v1(current) |
This version publication date |
02 Dec 2023
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First version publication date |
02 Dec 2023
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
MR41926
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04597918 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
F. Hoffmann-La Roche, Ltd.
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Sponsor organisation address |
Grenzacherstrasse 124, Basel, Switzerland, CH-4070
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Public contact |
F. Hoffmann-La Roche, Ltd., F. Hoffmann-La Roche, Ltd., +41 616878333, global.trial_information@roche.com
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Scientific contact |
F. Hoffmann-La Roche, Ltd., F. Hoffmann-La Roche, Ltd., +41 616878333, global.trial_information@roche.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
22 Dec 2022
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
22 Dec 2022
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Global end of trial reached? |
Yes
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Global end of trial date |
22 Dec 2022
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To explore the associations over time between clinical assessments, multimodal imaging assessments, aqueous humor (AH) biomarker patterns, and genetic polymorphisms
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Protection of trial subjects |
This study was conducted in full conformance with the ICH E6 guideline for Good Clinical Practice and the principles of the Declaration of Helsinki, or the laws and regulations of the country in which the research was conducted, whichever afforded the greater protection to the individual. All participants were required to read and sign an informed consent form prior to participation in the study.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
25 Nov 2020
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Argentina: 24
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Country: Number of subjects enrolled |
Canada: 10
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Country: Number of subjects enrolled |
Germany: 2
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Country: Number of subjects enrolled |
Italy: 4
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Country: Number of subjects enrolled |
Poland: 3
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Country: Number of subjects enrolled |
United Kingdom: 4
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Country: Number of subjects enrolled |
United States: 52
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Worldwide total number of subjects |
99
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EEA total number of subjects |
9
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
73
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From 65 to 84 years |
26
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||
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Pre-assignment
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Screening details |
A total of 99 patients were enrolled in the study at 23 sites in 7 countries. | ||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||
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Arms
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Arm title
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Faricimab | ||||||||||||||
Arm description |
Participants received 6 doses of faricimab (one 6-mg faricimab intravitreal [IVT] injection every 28 days [Q4W]) starting at Day 1 and ending on the Day 140 visit. Participants returned for a safety follow-up visit (SFV) after ≥28 days and within <35 days following their last study treatment. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
Faricimab
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Investigational medicinal product code |
RO6867461
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Other name |
Vabysmo
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravitreal use
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Dosage and administration details |
Patients were to receive 6 doses (one 6-mg faricimab intravitreal [IVT] injection once every 4 weeks [Q4W]) starting at Day 1 and ending on the Day 140 visit.
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Baseline characteristics reporting groups
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Reporting group title |
Faricimab
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Reporting group description |
Participants received 6 doses of faricimab (one 6-mg faricimab intravitreal [IVT] injection every 28 days [Q4W]) starting at Day 1 and ending on the Day 140 visit. Participants returned for a safety follow-up visit (SFV) after ≥28 days and within <35 days following their last study treatment. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Faricimab
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Reporting group description |
Participants received 6 doses of faricimab (one 6-mg faricimab intravitreal [IVT] injection every 28 days [Q4W]) starting at Day 1 and ending on the Day 140 visit. Participants returned for a safety follow-up visit (SFV) after ≥28 days and within <35 days following their last study treatment. | ||
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End point title |
Percentage of Participants with a ≥2-Step Improvement from Baseline on the Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) in the Study Eye at Week 24 [1] | ||||||||
End point description |
The ETDRS DRSS score of each participant's study eye was assessed using ultra-wide field color fundus photography (UWF-CFP) taken by trained personnel at the study sites. Analysis of the fundus photographs was performed by the central reading center, and the percentage of participants with a ≥2-step improvement from baseline was summarized along with a two-sided 95% Clopper-Pearson exact confidence interval. Baseline was defined as the participant's last observation prior to initiation of study drug. Participants in the modified intent-to-treat (mITT) Population with missing baseline assessments were excluded from the analysis. The number analyzed indicates participants with assessments at both Baseline and Week 24.
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End point type |
Primary
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End point timeframe |
Baseline and Week 24
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This was an exploratory, open-label, single-arm study. The results were summarized using descriptive statistics. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants with Absence of Intraretinal Fluid in the Study Eye at Week 24 | ||||||||
End point description |
The absence of intraretinal fluid (IRF) in the study eye (defined as IRF absent or definite outside center subfield only) was assessed by the central reading center using Spectral Domain-Optical Coherence Tomography (SD-OCT). The percentage of participants with absence of IRF and a two-sided 95% Clopper-Pearson exact confidence interval are reported. Participants in the modified intent-to-treat (mITT) Population with non-missing Week 24 assessments were included in the analysis.
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End point type |
Secondary
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End point timeframe |
Week 24
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| No statistical analyses for this end point | |||||||||
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End point title |
Median Time to First Absence of DME in the Study Eye During the Study | ||||||||
End point description |
An event was defined as the first absence of diabetic macular edema (DME) in the study eye, defined as first time reaching central subfield thickness (CST; ILM-RPE) <305 microns, after baseline. Baseline was defined as the participant's last observation prior to initiation of study drug. The time to first absence of DME was a Kaplan-Meier estimate. The 95% confidence interval (CI) for the median was computed using the method of Brookmeyer and Crowley. Participants without an event and discontinued from treatment were censored at the last CST assessment. Participants with absence of DME at Baseline were excluded from the analysis.
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End point type |
Secondary
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End point timeframe |
From Baseline to Week 24
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| No statistical analyses for this end point | |||||||||
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End point title |
Adjusted Mean Change from Baseline in Best-Corrected Visual Acuity (BCVA) in the Study Eye at Week 24 | ||||||||
End point description |
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. For the Mixed Model for Repeated Measures (MMRM) analysis, the model adjusted for visit, age (continuous), baseline BCVA (continuous), and region (US and Canada and the rest of the world). An unstructured covariance structure was used. In case of convergence issues with the model, an AR (1) covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM.
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End point type |
Secondary
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End point timeframe |
From Baseline to Week 24
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| No statistical analyses for this end point | |||||||||
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End point title |
Adjusted Mean Change from Baseline in Central Subfield Thickness in the Study Eye at Week 24 | ||||||||
End point description |
Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and the retinal pigment epithelium (RPE) using Spectral Domain-Optical Coherence Tomography (SD-OCT), as assessed by the central reading center. For the Mixed Model of Repeated Measures (MMRM) analysis, the model was adjusted for visit, age (continuous), baseline CST (continuous), and region (US and Canada and the rest of the world). An unstructured covariance structure was used. In case of convergence issues with the model, an AR (1) covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM.
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End point type |
Secondary
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End point timeframe |
From Baseline to Week 24
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants with Absence of Subretinal Fluid in the Study Eye at Week 24 | ||||||||
End point description |
The absence of subretinal fluid (SRF) in the study eye (defined as SRF absent or definite outside center subfield only) was assessed by the central reading center using Spectral Domain-Optical Coherence Tomography (SD-OCT). The percentage of participants with absence of SRF and a two-sided 95% Clopper-Pearson exact confidence interval are reported. Participants in the modified intent-to-treat (mITT) Population with non-missing Week 24 assessments were included in the analysis.
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End point type |
Secondary
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End point timeframe |
Week 24
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
From first dose of study drug until ≥28 days to <35 days after the last dose of study drug (up to 24 weeks)
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Adverse event reporting additional description |
Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of faricimab in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
25.1
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Reporting groups
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Reporting group title |
Faricimab
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Reporting group description |
Participants received 6 doses of faricimab (one 6-mg faricimab intravitreal [IVT] injection every 28 days [Q4W]) starting at Day 1 and ending on the Day 140 visit. Participants returned for a safety follow-up visit (SFV) after ≥28 days and within <35 days following their last study treatment. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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25 Mar 2021 |
Protocol version 2: •The AC paracentesis-associated risk of cataract induction was added as requested in the list of grounds for non-acceptance in the EU; •The bulbar tension was to be assessed manually after the AH tap. If the bulbar
tension was deemed too low to be able to perform a safe IVT injection, as per the treatment administrator’s discretion, a re-toning with saline solution was to be performed through a paracentesis; •Correction that ultra-wide field fundus fluorescein angiography was to also be collected for the non-study eye at the Day 140 visit; •Clarification that ocular assessments at the screening visit were to be performed for both eyes at the time of screening, as it was not confirmed yet
which eye would be the study eye; •Inclusion of the option of continued access to faricimab based on primary endpoint results of the faricimab DME Phase III study data; •Clarification that patients with ocular disease other than DME, which could
preclude in the opinion of the investigator acquisition |
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05 May 2021 |
Protocol version 3: •Inclusion criterion 8 (ETDRS DRSS) was removed; •Exclusion criterion 22 (ETDRS DRSS) was modified; •Clarification that patients screen failed solely due to the DRSS criteria in protocol versions 1 and 2 that met all of the inclusion criteria in protocol version 3 could be re-screened |
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18 Feb 2022 |
Protocol version 4: •Benefit-risk assessment was updated to align with the faricimab Investigator’s Brochure; •Clarification was added to the sample size of study population to compensate for those patients that do not have a complete set of analyzable AH samples; •The responsibilities of the investigator and the role of the medical monitor in determining patient eligibility was clarified; •Total length of the study was extended; •Language was added to indicate that systemic corticosteroids also included inhaled corticosteroids from inhalers used regularly (eg, pulmonary disease, asthma, or seasonal allergy); •Additional guidance regarding patients using inhaled corticosteroids occasionally (PRN) was added; •Exclusion criterion #29 was clarified to also exclude some laser procedures that could interfere with AH production; •Additional guidance regarding the fellow (non-study) eye treatment with anti-vascular endothelial growth factor therapy was added; •Clarification that continuous usage of topical ophthalmic corticosteroids for 100 days or more was considered prohibited therapy, and added the medications claiming to have an effect on macular pathology to the list of
prohibited therapies; •Clarification added that the same device must be used to assess the patient’s pre-treatment IOP and their post-treatment IOP; •Language was added to clarify that adverse events associated with a special situation that also qualify as adverse events of special interest were to be
reported within 24 hours |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
