Macular Edema, DiabeticPhase 2NCT01994291
A Phase 2, Multi-Center Study To Compare The Efficacy And Safety Of A Chemokine CCR2/5 Receptor Antagonist With Ranibizumab In Adults With Diabetic Macular Edema
A Phase 2 study testing Ranibizumab and PF-04634817 in people with Macular Edema, Diabetic, run by Pfizer at 63 sites in 9 countries.
Trial summary
The study hypothesis under test is that administration of the CCR2/5 antagonist has the potential to be as effective as the current treatment options for subjects with diabetic macular edema. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Macular Edema, Diabetic
- What is being tested?
- Ranibizumab and PF-04634817
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 199 participants
- Where
- 63 sitesin 9 countries
- Study dates
- Nov 2013to Aug 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with Diabetes Mellitus (Type 1 or Type 2) Showing Diabetic Macular Edema in the Eye
- Reduced visual acuity resulting from retinal thickening
- Female subjects of non-childbearing potential ≥18 years and male subjects greater than or equal to 18 years. A subject is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active.
- Female subjects who are not of childbearing potential must meet at least one of the following criteria:
- Have undergone a documented hysterectomy and/or bilateral oophorectomy;
- Have medically confirmed ovarian failure; or
- Achieved post-menopausal status, defined as: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and have a serum follicle stimulating hormone (FSH) level within the laboratory's reference range for postmenopausal females.
Who cannot join
- Severe Impaired Renal Function
- Any intraocular condition or previous surgery in either eye that would likely require medical or surgical intervention during the study duration or if allowed to progress untreated for the 16 weeks of study duration, would likely contribute to a reduction in visual acuity.
Trial locations and contacts
63 sites in 9 countries.
63 sites in 9 countries
United States33 sites
Retina Institute of California
Arcadia, California, 91007
Southeast Retina Center, PC
Augusta, Georgia, 30909
Brain B.Berger,MD,PA
Austin, Texas, 78705
Retina Research Center
Austin, Texas, 78705
Retina Vitreous Associates Medical Group
Beverly Hills, California, 90211
Tufts Medical Center
Boston, Massachusetts, 02111
Retinal Diagnostic Center
Campbell, California, 95008
Charlotte Eye Ear Nose and Throat Associates PA
Charlotte, North Carolina, 28210
Retina Associates of Cleveland, Inc.
Cleveland, Ohio, 44122
Retina Consultants of Houston, PA
Houston, Texas, 77030
Midwest Eye Institute
Indianapolis, Indiana, 46290
TLC Eyecare & Laser Center
Jackson, Michigan, 49202
Retina Associates of Orange County
Laguna Hills, California, 92653
Bascom Palmer Eye Institute
Miami, Florida, 33136
New England Retina Associates
New London, Connecticut, 06320
Dean McGee Eye Institute
Oklahoma City, Oklahoma, 73104
University of Oklahoma -OU Physicians
Oklahoma City, Oklahoma, 73104
Southern California Desert Retina Consultants
Palm Desert, California, 92211
Retina Research Institute, LLC
Phoenix, Arizona, 85014
Retinal Consultants of Arizona
Phoenix, Arizona, 85014
Sunny View Medical Center
Phoenix, Arizona, 85018
Premier Research Group Limited
Phoenix, Arizona, 85027
Retina Vitreous Consultants
Pittsburgh, Pennsylvania, 15213
Fort Lauderdale Eye Institute
Plantation, Florida, 33324
Black Hills Regional Eye Institute
Rapid City, South Dakota, 57701
Wm Beaumont Medical Office Building
Royal Oak, Michigan, 48073
Rocky Mountain Retina Consultants
Salt Lake City, Utah, 84107
Medical Center Ophthalmology Associates
San Antonio, Texas, 78240
Retina Centers, P.C.
Tucson, Arizona, 85704
Associates in Ophthalmology Ltd
West Mifflin, Pennsylvania, 15122
American Institute of Research (Administrative Only)
Whittier, California, 90603
Center for Retina and Macular Disease
Winter Haven, Florida, 33880
Retina Associates of Cleveland
Youngstown, Ohio, 44505
Germany8 sites
Charite - Universitaetsmedizin Berlin, Campus Benjamin Franklin
Berlin, 12200
Universitaetsmedizin Goettingen
Göttingen, 37075
Universitatsmedizin Mainz
Mainz, 55131
Universitaetsklinikum Muenster
Münster, Germany, 48159
Augenärzte am St. Franziskus-Hospital
Münster, 48145
Universitätsklinikum Regensburg
Regensburg, Bavaria, 93053
Knappschaftsklinikum GmbH
Sulzbach, 66280
Universitatsklinikum Tubingen
Tübingen, 72076
Czechia6 sites
Fakultní nemocnice Hradec Králové, Ocni klinika
Hradec Králové, 500 05
Fakultní nemocnice Hradec Králové, Nemocnicni lekarna
Hradec Králové, 50005
Fakultni nemocnice Ostrava, lekarna
Ostrava - Poruba, 70852
Fakultni nemocnice Ostrava, Ocni klinika
Ostrava - Poruba, 70852
Fakultni nemocnice Kralovske Vinohrady, Oftalmologicka klinika
Prague, 10034
Fakultni nemocnice Kralovske Vinohrady, Ustavni lekarna
Prague, 10034
Hungary6 sites
Semmelweis Egyetem, Szemészeti Klinika
Budapest, 1083
Bajcsy-Zsilinszky Korhaz, Szemeszet
Budapest, 1106
Budapest Retina Associates Kft.
Budapest, 1133
Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum, Szemklinika
Debrecen, 4032
Ganglion Orvosi Kozpont
Pécs, 7621
Csolnoky Ferenc Korhaz, Szemeszeti Osztaly
Veszprém, 8200
Israel5 sites
Hadassah Medical Organization, Hadassah Medical Center, Ein Karem
Jerusalem, 91120
Meir Medical Center
Kfar Saba, 44281
Rabin Medical Center, Beilinson Hospital
Petah Tikva, 49100
Kaplan Medical Center
Rehovot, 76100
Tel Aviv Sourasky Medical Center
Tel Aviv, 64239
Romania2 sites
Med Life SA, Sectia Oftalmologie
Bucharest, 010719
Institutul National de Diabet, Nutritie si Boli Metabolice "N.C.Paulescu"
Bucharest, 020475
Poland1 site
Uniwersytecki Szpital Kliniczny Im. Jana Mikulicza Radeckiego We Wrocławiu, Klinika Okulistyki
Wroclaw, 50-367
About this study
Official title: A Phase 2, Randomized, Double-Masked, Placebo-Controlled, Parallel Group, Multi-Center Study To Compare The Efficacy And Safety Of A Chemokine CCR2/5 Receptor Antagonist (PF-04634817) With That Of Ranibizumab In Adult Subjects With Diabetic Macular Edema
The study hypothesis under test is that administration of the CCR2/5 antagonist has the potential to be as effective as the current treatment options for subjects with diabetic macular edema. The current treatment option for these subjects is an injection directly into the eye, while this CCR2/5 antagonist would be an oral drug which has the potential to be just as effective. This CCR2/5 antagonist also has a broader anti-inflammatory potential and might be able to provide an alternative mechanism to treat Diabetic Macular Edema.
Read the detailed description
Study recruitment was stopped on April 9, 2015. This decision was taken for business reasons due to changes in the prioritization of the drug development portfolio. This decision was not as a result of any evolving safety, efficacy issue or changes in the risk:benefit assessment of this product or regulatory interactions.
- Conditions
- Macular Edema, Diabetic
- Being tested
- Ranibizumab, Placebo, PF-04634817, Masked Sham Therapy
- Keywords
- Chemokine Antagonist, Diabetic Macular Edema, Diabetes, Diabetes Mellitus, Macular Edema, Diabetic Retinopathy, Anti-VEGF
- Medical subject headings
- Macular Edema, Diabetes Mellitus, Diabetic Retinopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RanibizumabDrug
Intravitreal Injection supplied as:
- 10 mg/mL in a 0.2 mL vial with instructions on preparation and administration of the 0.5 mg (0.05 mL) dose.
- 6 mg/mL in a single use vial with instructions on preparation and administration of the 0.3 mg (0.05 mL) dose.
- Adminstered once a month for 12 weeks
PlaceboDrug
Oral Placebo is provided in tablet form to match the 50mg dose of PF-04634817.
Dose is 4 tablets each day for 12 weeks
PF-04634817Drug
Four 50mg tablets PF-04634817 once a day for 12 weeks.
Masked Sham TherapyDrug
Empty, needle-less syringe is used by the unmasked team once a month.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Active comparator | Intravitreal administration of ranibizumab (either 0.3 or 0.5 mg, given monthly, as detailed in the prescribing information and label content approved for the country governing the study site) plus an oral placebo. Receives: Drug: Ranibizumab; Drug: Placebo |
| Arm 2 | Experimental | Oral PF-04634817 200 mg, once daily plus a masked sham therapy (given monthly). Receives: Drug: PF-04634817; Drug: Masked Sham Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Letter Change From Baseline at Week 12 in Best Corrected Visual Acuity (BCVA)
Refraction and visual acuity were assessed through the BCVA obtained using the retro illuminated early treatment diabetic retinopathy study (ETDRS) charts. Distance visual acuity was expressed as an ETDRS score (number of letters correctly read).
Measured: Baseline (Day 0) and Week 12
Secondary outcomes (5)
Proportion of Subjects Gaining 15 ETDRS Letters in BCVA From Baseline at Week 12
Refraction and visual acuity were assessed through the BCVA obtained using the retro illuminated ETDRS charts. Distance visual acuity was expressed as an ETDRS score (number of letters correctly read).
Measured: Baseline (Day 0) and Week 12
Mean Change From Baseline in Central Subfield Retinal Thickness in the Study Eye at Week 12
A central reading center was used for the evaluation. A photographer or technician pre certified ("study certified") by the Central Reading Center ought to perform all optical coherence tomography (OCT) imaging. Use of a Spectralis or Cirrus OCT was acceptable.
Measured: Baseline (Day 0) and Week 12
Mean Change From Baseline in The Area of Fluorescein Leakage in the Study Eye at Week 12
Fluorescein Angiography (FA) using certified digital systems was taken by a photographer who had been pre-certified ("study-certified") by the Central Reading Center. They were evaluated by the Central Reading Center.
Measured: Baseline (Day 0) and Week 12
Mean Change From Baseline in Steps of Diabetic Retinopathy Step (ETDRS Severity Scale) in the Study Eye at Week 12
Stereo color fundus photographs using certified digital systems were taken by a photographer who had been pre-certified ("study certified") by the Central Reading Center. They were evaluated by the Central Reading Center.
Measured: Baseline (Day 0) and Week 12
Plasma Concentration of PF-04634817 up to Week 12
Measured: Week 0, Week 4, Week 8, and Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2013 (estimated)
- Study startNov 2013
- Primary completionAug 2015
- Study completionAug 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Macular Edema, DiabeticStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 199 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01994291
- Sponsor's protocol ID
- B1261009
- Other IDs
- 2013-003147-27
- Status last verified
- Aug 2016
- First submitted
- 8 Nov 2013
- Last updated
- 17 Oct 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Gale JD, Berger B, Gilbert S, Popa S, Sultan MB, Schachar RA, Girgenti D, Perros-Huguet C. A CCR2/5 Inhibitor, PF-04634817, Is Inferior to Monthly Ranibizumab in the Treatment of Diabetic Macular Edema. Invest Ophthalmol Vis Sci. 2018 May 1;59(6):2659-2669. doi: 10.1167/iovs.17-22731.
PubMed 29847672
Study at a glance
From the registry record, last updated by the sponsor on 17 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Randomized, Double-Masked, Placebo-Controlled, Parallel Group, Multi-Center Study To Compare The Efficacy And Safety Of A Chemokine CCR2/5 Receptor Antagonist (PF-04634817) With That Of Ranibizumab In Adult Subjects With Diabetic Macular Edema
- ClinicalTrials.gov ID
- NCT01994291
- Acronym / sponsor ID
- B1261009
- Conditions
- Macular Edema, Diabetic
- Keywords
- Chemokine Antagonist, Diabetic Macular Edema, Diabetes, Diabetes Mellitus, Macular Edema, Diabetic Retinopathy, Anti-VEGF
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 199 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- Nov 2013
- Primary completion
- Aug 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 25 Nov 2013 (estimated)
- Results
- Posted 17 Oct 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study hypothesis under test is that administration of the CCR2/5 antagonist has the potential to be as effective as the current treatment options for subjects with diabetic macular edema. The current treatment option for these subjects is an injection directly into the eye, while this CCR2/5 antagonist would be an oral drug which has the potential to be just as effective. This CCR2/5 antagonist also has a broader anti-inflammatory potential and might be able to provide an alternative mechanism to treat Diabetic Macular Edema.
Detailed description
Study recruitment was stopped on April 9, 2015. This decision was taken for business reasons due to changes in the prioritization of the drug development portfolio. This decision was not as a result of any evolving safety, efficacy issue or changes in the risk:benefit assessment of this product or regulatory interactions.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Active comparator | Drug: Ranibizumab, Drug: PlaceboIntravitreal administration of ranibizumab (either 0.3 or 0.5 mg, given monthly, as detailed in the prescribing information and label content approved for the country governing the study site) plus an oral placebo. |
| Arm 2 | Experimental | Drug: PF-04634817, Drug: Masked Sham TherapyOral PF-04634817 200 mg, once daily plus a masked sham therapy (given monthly). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patients with Diabetes Mellitus (Type 1 or Type 2) Showing Diabetic Macular Edema in the Eye
- Reduced visual acuity resulting from retinal thickening
- Female subjects of non-childbearing potential ≥18 years and male subjects greater than or equal to 18 years. A subject is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active.
- Female subjects who are not of childbearing potential must meet at least one of the following criteria:
Key exclusion criteria (2 listed)
- Severe Impaired Renal Function
- Any intraocular condition or previous surgery in either eye that would likely require medical or surgical intervention during the study duration or if allowed to progress untreated for the 16 weeks of study duration, would likely contribute to a reduction in visual acuity.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RanibizumabIntravitreal Injection supplied as: * 10 mg/mL in a 0.2 mL vial with instructions on preparation and administration of the 0.5 mg (0.05 mL) dose. * 6 mg/mL in a single use vial with instructions on preparation and administration of the 0.3 mg (0.05 mL) dose. * Adminstered once a month for 12 weeks | Drug | Arm 1 |
| PlaceboOral Placebo is provided in tablet form to match the 50mg dose of PF-04634817. Dose is 4 tablets each day for 12 weeks | Drug | Arm 1 |
| PF-04634817Four 50mg tablets PF-04634817 once a day for 12 weeks. | Drug | Arm 2 |
| Masked Sham TherapyEmpty, needle-less syringe is used by the unmasked team once a month. | Drug | Arm 2 |
Primary outcome
Mean Letter Change From Baseline at Week 12 in Best Corrected Visual Acuity (BCVA)
Time frame: Baseline (Day 0) and Week 12
Refraction and visual acuity were assessed through the BCVA obtained using the retro illuminated early treatment diabetic retinopathy study (ETDRS) charts. Distance visual acuity was expressed as an ETDRS score (number of letters correctly read).
5 secondary outcomes
Proportion of Subjects Gaining 15 ETDRS Letters in BCVA From Baseline at Week 12
Time frame: Baseline (Day 0) and Week 12
Mean Change From Baseline in Central Subfield Retinal Thickness in the Study Eye at Week 12
Time frame: Baseline (Day 0) and Week 12
Mean Change From Baseline in The Area of Fluorescein Leakage in the Study Eye at Week 12
Time frame: Baseline (Day 0) and Week 12
Mean Change From Baseline in Steps of Diabetic Retinopathy Step (ETDRS Severity Scale) in the Study Eye at Week 12
Time frame: Baseline (Day 0) and Week 12
Plasma Concentration of PF-04634817 up to Week 12
Time frame: Week 0, Week 4, Week 8, and Week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Oct 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29847672Gale JD, Berger B, Gilbert S, Popa S, Sultan MB, Schachar RA, Girgenti D, Perros-Huguet C. A CCR2/5 Inhibitor, PF-04634817, Is Inferior to Monthly Ranibizumab in the Treatment of Diabetic Macular Edema. Invest Ophthalmol Vis Sci. 2018 May 1;59(6):2659-2669. doi: 10.1167/iovs.17-22731.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
63 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ranibizumab and PF-04634817 in people with Macular Edema, Diabetic, run by Pfizer at 63 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 63 sites in United States, Germany, Czechia, Hungary, Israel and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Oct 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Letter Change From Baseline at Week 12 in Best Corrected Visual Acuity (BCVA) (time frame: Baseline (Day 0) and Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01994291, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Oct 2016.