Diabetic Macular Edema
Conditions
Brief summary
Study BP43445 is a phase II, multicenter, randomized, double-masked, active comparator-controlled study to investigate the efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of vamikibart administered intravitreally in participants with diabetic macular edema. Only one eye will be chosen as the study eye. The duration of the study will be up to 76 weeks.
Interventions
DRUGVamikibart
Vamikibart will be administered by IVT injection as specified in each treatment arm.
DRUGRanibizumab
Ranibizumab 0.5 mg will be administered to the participants by IVT injection, as specified in the treatment arm.
OTHERSham Procedure
Sham is a procedure that mimics an IVT injection and involves the blunt end of an empty syringe (without a needle) being pressed against the anesthetized eye. Sham procedure will be administered to participants in the Q8W arms at applicable visits to maintain masking between treatment arms.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of diabetes mellitus (Type 1 or Type 2) * Macular thickening secondary to diabetic macular edema (DME) involving the center of the macula * Decreased visual acuity attributable primarily to DME * Ability and willingness to provide written informed consent and to comply with the study protocol * Willingness to allow Aqueous Humor collection * For women of childbearing potential: agreement to remain abstinent or use at least one highly effective contraceptive method that results in a failure rate of \<1% per year during the treatment period and for at least 12 weeks after the final dose of study treatment
Exclusion criteria
* Hemoglobin A1c (HbA1c) of greater than (\>) 12% * Uncontrolled blood pressure, defined as a systolic value greater than (\>)180 millimeters of mercury (mmHg) and/or a diastolic value \>100 mmHg while a patient is at rest * Currently pregnant or breastfeeding, or intend to become pregnant during the study * Prior treatment with panretinal photocoagulation or macular laser to the study eye * Any intraocular or periocular corticosteroid treatment within the past 16 weeks prior to Day 1 to the study eye * Prior Iluvien or Retisert implants within 3 years prior to Day 1 to the study eye * Prior or concomitant treatment with anti-VEGF therapy within 8 weeks prior to Day 1 to the study eye; Vabysmo\^TM within 16 weeks prior to Day 1, prior Beovu® is not permitted * Prior administration of IVT brolucizumab (Beovu®): ever; vamikibart: \</=24 weeks prior to Day 1) in either eye * Any proliferative diabetic retinopathy * Active intraocular or periocular infection or active intraocular inflammation in the study eye * Any current or history of ocular disease other than DME that may confound assessment of the macula or affect central vision in the study eye * Any current ocular condition which, in the opinion of the investigator, is currently causing or could be expected to contribute to irreversible vision loss due to a cause other than DME in the study eye * Other protocol-specified inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Best-Corrected Visual Acuity (BCVA) Averaged Over Week 44 and Week 48, in Treatment-naïve Participants | Baseline, Weeks 44 and 48 | The BCVA, at a starting test distance of 4 meters (m), was measured for both eyes, prior to dilating eyes by using the set of three Precision visionTM or Lighthouse distance acuity charts (modified early treatment diabetic retinopathy study \[ETDRS\] charts 1, 2 and R) by trained and certified personnel at the study sites and at each study visit. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. This analysis used a Mixed Model for Repeated Measurements (MMRM) model. Adjusted mean has been reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Avoiding a Loss of ≥ 15, ≥ 10, or ≥ 5 Letters in BCVA From Baseline Over Time, in Overall Enrolled Population | From baseline up to Week 72 | The BCVA, at a starting test distance of 4 m, was measured for both eyes, prior to dilating eyes by using the set of three Precision visionTM or Lighthouse distance acuity charts (modified ETDRS charts 1, 2 and R) by trained and certified personnel at the study sites and at each study visit. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. Percentages have been summarized. |
| Percentage of Participants With BCVA ≥ 69 Letters (20/40 Snellen Equivalent) Over Time, in Overall Enrolled Population | Baseline, Weeks 1, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72 | The BCVA, at a starting test distance of 4 m, was measured for both eyes, prior to dilating eyes by using the set of three Precision visionTM or Lighthouse distance acuity charts (modified ETDRS charts 1, 2 and R) by trained and certified personnel at the study sites and at each study visit. The BCVA letter score ranges from 0 (Snellen equivalent \<20/800) to 100 (Snellen equivalent of 20/10) letters. A gain in BCVA letter score from baseline indicates an improvement in visual acuity. Percentages have been summarized. |
| Percentage of Participants With BCVA ≥ 84 Letters (20/20 Snellen Equivalent) Over Time, in Overall Enrolled Population | Baseline, Weeks 1, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72 | The BCVA, at a starting test distance of 4 m, was measured for both eyes, prior to dilating eyes by using the set of three Precision visionTM or Lighthouse distance acuity charts (modified ETDRS charts 1, 2 and R) by trained and certified personnel at the study sites and at each study visit. The BCVA letter score ranges from 0 (Snellen equivalent \<20/800) to 100 (Snellen equivalent of 20/10) letters. A gain in BCVA letter score from baseline indicates an improvement in visual acuity. Percentages have been summarized. |
| Number of Participants With Systemic and Ocular Adverse Events (AEs) | Up to Week 72 | An AE was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Systemic AEs include all non-ocular AEs. Only one eye was selected as the study eye, while the other was referred to as the fellow eye. |
| Change From Baseline in BCVA Averaged Over Week 44 and Week 48, in Previously Treated Participants | Baseline, Weeks 44 and 48 | The BCVA, at a starting test distance of 4 m, was measured for both eyes, prior to dilating eyes by using the set of three Precision visionTM or Lighthouse distance acuity charts (modified ETDRS charts 1, 2 and R) by trained and certified personnel at the study sites and at each study visit. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. This analysis used a MMRM model. Adjusted mean has been reported. |
| Change From Baseline in BCVA Averaged Over Week 44 and Week 48, in Overall Enrolled Population | Baseline, Weeks 44 and 48 | The BCVA, at a starting test distance of 4 m, was measured for both eyes, prior to dilating eyes by using the set of three Precision visionTM or Lighthouse distance acuity charts (modified ETDRS charts 1, 2 and R) by trained and certified personnel at the study sites and at each study visit. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. This analysis used a MMRM model. Adjusted mean has been reported. |
| Change From Baseline in BCVA Averaged Over Week 32 and Week 36, in Treatment-naïve Participants | Baseline, Weeks 32 and 36 | The BCVA, at a starting test distance of 4 m, was measured for both eyes, prior to dilating eyes by using the set of three Precision visionTM or Lighthouse distance acuity charts (modified ETDRS charts 1, 2 and R) by trained and certified personnel at the study sites and at each study visit. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. This analysis used a MMRM model. Adjusted mean has been reported. |
| Change From Baseline in BCVA Averaged Over Week 32 and Week 36, in Previously Treated Participants | Baseline, Weeks 32 and 36 | The BCVA, at a starting test distance of 4 m, was measured for both eyes, prior to dilating eyes by using the set of three Precision visionTM or Lighthouse distance acuity charts (modified ETDRS charts 1, 2 and R) by trained and certified personnel at the study sites and at each study visit. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. This analysis used a MMRM model. Adjusted mean has been reported. |
| Change From Baseline in BCVA Averaged Over Week 32 and Week 36, in Overall Enrolled Population | Baseline, Weeks 32 and 36 | The BCVA, at a starting test distance of 4 m, was measured for both eyes, prior to dilating eyes by using the set of three Precision visionTM or Lighthouse distance acuity charts (modified ETDRS charts 1, 2 and R) by trained and certified personnel at the study sites and at each study visit. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. This analysis used a MMRM model. Adjusted mean has been reported. |
| Change From Baseline in BCVA Averaged Over Week 20 and Week 24, in Treatment-naïve Participants | Baseline, Weeks 20 and 24 | The BCVA, at a starting test distance of 4 m, was measured for both eyes, prior to dilating eyes by using the set of three Precision visionTM or Lighthouse distance acuity charts (modified ETDRS charts 1, 2 and R) by trained and certified personnel at the study sites and at each study visit. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. This analysis used a MMRM model. Adjusted mean has been reported. |
| Change From Baseline in BCVA Averaged Over Week 20 and Week 24, in Previously Treated Participants | Baseline, Weeks 20 and 24 | The BCVA, at a starting test distance of 4 m, was measured for both eyes, prior to dilating eyes by using the set of three Precision visionTM or Lighthouse distance acuity charts (modified ETDRS charts 1, 2 and R) by trained and certified personnel at the study sites and at each study visit. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. This analysis used a MMRM model. Adjusted mean has been reported. |
| Change From Baseline in BCVA Averaged Over Week 20 and Week 24, in Overall Enrolled Population | Baseline, Weeks 20 and 24 | The BCVA, at a starting test distance of 4 m, was measured for both eyes, prior to dilating eyes by using the set of three Precision visionTM or Lighthouse distance acuity charts (modified ETDRS charts 1, 2 and R) by trained and certified personnel at the study sites and at each study visit. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. This analysis used a MMRM model. Adjusted mean has been reported. |
| Change From Baseline in BCVA Over Time, in Overall Enrolled Population | Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72 | The BCVA, at a starting test distance of 4 m, was measured for both eyes, prior to dilating eyes by using the set of three Precision visionTM or Lighthouse distance acuity charts (modified ETDRS charts 1, 2 and R) by trained and certified personnel at the study sites and at each study visit. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. This analysis used a MMRM model. Adjusted mean has been reported. |
| Percentage of Participants Gaining Greater Than or Equal to (≥) 15, ≥ 10, ≥ 5, or ≥ 0 Letters in BCVA From Baseline Over Time, in Overall Enrolled Population | From baseline up to Week 72 | The BCVA, at a starting test distance of 4 m, was measured for both eyes, prior to dilating eyes by using the set of three Precision visionTM or Lighthouse distance acuity charts (modified ETDRS charts 1, 2 and R) by trained and certified personnel at the study sites and at each study visit. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. Percentages have been summarized. |
| Percentage of Participants With BCVA of Less Than or Equal to (≤) 38 Letters (Snellen Equivalent 20/200) Over Time, in Overall Enrolled Population | Baseline, Weeks 1, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72 | The BCVA, at a starting test distance of 4 m, was measured for both eyes, prior to dilating eyes by using the set of three Precision visionTM or Lighthouse distance acuity charts (modified ETDRS charts 1, 2 and R) by trained and certified personnel at the study sites and at each study visit. The BCVA letter score ranges from 0 (Snellen equivalent \<20/800) to 100 (Snellen equivalent of 20/10) letters. A gain in BCVA letter score from baseline indicates an improvement in visual acuity. Percentages have been summarized. |
| Change From Baseline in Central Subfield Thickness (CST) Averaged Over Weeks 44 and 48, in Treatment-naïve Participants | Baseline, Weeks 44 and 48 | CST was defined as the distance between the internal limiting membrane (ILM) and the retinal pigment epithelium (RPE), measured using Spectral Domain-Optical Coherence Tomography (SD-OCT). This analysis used a MMRM model. Adjusted mean has been reported. |
| Change From Baseline in CST Averaged Over Weeks 44 and 48, in Previously Treated Participants | Baseline, Weeks 44 and 48 | CST was defined as the distance between the ILM and the RPE, measured using SD-OCT. This analysis used a MMRM model. Adjusted mean has been reported. |
| Change From Baseline in CST Averaged Over Weeks 44 and 48, in Overall Enrolled Population | Baseline, Weeks 44 and 48 | CST was defined as the distance between the ILM and the RPE, measured using SD-OCT. This analysis used a MMRM model. Adjusted mean has been reported. |
| Change From Baseline in CST Averaged Over Weeks 32 and 36, in Treatment-naïve Participants | Baseline, Weeks 32 and 36 | CST was defined as the distance between the ILM and the RPE, measured using SD-OCT. This analysis used a MMRM model. Adjusted mean has been reported. |
| Change From Baseline in CST Averaged Over Weeks 32 and 36, in Previously Treated Participants | Baseline, Weeks 32 and 36 | CST was defined as the distance between the ILM and the RPE, measured using SD-OCT. This analysis used a MMRM model. Adjusted mean has been reported. |
| Change From Baseline in CST Averaged Over Weeks 32 and 36, in Overall Enrolled Population | Baseline, Weeks 32 and 36 | CST was defined as the distance between the ILM and the RPE, measured using SD-OCT. This analysis used a MMRM model. Adjusted mean has been reported. |
| Change From Baseline in CST Averaged Over Weeks 20 and 24, in Treatment-naïve Participants | Baseline, Weeks 20 and 24 | CST was defined as the distance between the ILM and the RPE, measured using SD-OCT. This analysis used a MMRM model. Adjusted mean has been reported. |
| Change From Baseline in CST Averaged Over Weeks 20 and 24, in Previously Treated Participants | Baseline, Weeks 20 and 24 | CST was defined as the distance between the ILM and the RPE, measured using SD-OCT. This analysis used a MMRM model. Adjusted mean has been reported. |
| Change From Baseline in CST Averaged Over Weeks 20 and 24, in Overall Enrolled Population | Baseline, Weeks 20 and 24 | CST was defined as the distance between the ILM and the RPE, measured using SD-OCT. This analysis used a MMRM model. Adjusted mean has been reported. |
| Change From Baseline in CST Over Time, in Overall Enrolled Population | Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72 | CST was defined as the distance between the ILM and the RPE, measured using SD-OCT. This analysis used a MMRM model. Adjusted mean has been reported. |
| Percentage of Participants With Absence of DME Over Time, in Overall Enrolled Population | Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72 | Absence of DME was defined as CST \< 325 µm for spectralis SD-OCT, or \< 315 μm for cirrus SD-OCT or topcon SD-OCT. SD-OCT was performed on a Spectralis instrument. Percentages have been summarized. |
| Percentage of Participants With Absence of Intraretinal Fluid (IRF) Over Time, in Overall Enrolled Population | Baseline, Weeks 4, 12, 24, 36, 48, and 72 | The absence of IRF in the study eye (defined as IRF absent or definite outside center subfield only) was assessed by the central reading center using SD-OCT. The percentage of participants with the absence of IRF at the foveal center were reported. Percentages have been summarized. |
| Percentage of Participants With Absence of Subretinal Fluid (SRF) Over Time, in Overall ITT Population | Baseline, Weeks 4, 12, 24, 36, 48, and 72 | The absence of SRF in the study eye (defined as SRF absent or definite outside center subfield only) was assessed by the central reading center using SD-OCT. The percentage of participants with absence of SRF at the foveal center were reported. Percentages have been summarized. |
Countries
Argentina, Canada, Czechia, Poland, Puerto Rico, South Korea, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Participant flow
Recruitment details
A total of 394 participants with diabetic macular edema (DME) took part in the study at 74 investigative sites across Argentina, Canada, Czech Republic, Spain, Republic of Korea, Poland, the United Kingdom and the United States from 31 December 2021 to 21 April 2025.
Pre-assignment details
Participants were randomized into 1:1:1:1 ratio to 4-parallel arms- 0.25 milligrams (mg) Vamikibart every 8th week (Q8W), 1 mg Vamikibart Q8W, 1 mg Vamikibart every 4th week (Q4W), and 0.5 mg Ranibizumab Q4W, to receive treatment up to Week 44, followed by off-treatment observation.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 62.5 years STANDARD_DEVIATION 9.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 15 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 47 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 149 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 4 Participants |
| Race (NIH/OMB) Asian | 5 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 37 Participants |
| Race (NIH/OMB) White | 180 Participants |
| Sex: Female, Male Female | 184 Participants |
| Sex: Female, Male Male | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 94 | 1 / 100 | 1 / 98 | 1 / 98 |
| other Total, other adverse events | 25 / 94 | 40 / 100 | 36 / 98 | 32 / 98 |
| serious Total, serious adverse events | 17 / 94 | 25 / 100 | 21 / 98 | 20 / 98 |
Outcome results
None listed