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Phase 1

Age-Related Maculopathy | Monoclonal antibody | Ophthalmology |Pfizer, Inc.|Last Updated: May 12, 2022

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindUNCONTROLLEDBiomarker
Total Trials2
Total Enrollment81
FDA Designations
No designations recorded
Clinical Trials (2)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT01003691Safety And Tolerability Study Of RN6G In Subjects With Advanced Dry, Age-Related Macular Degeneration Including Geographic AtrophyPHASE1 COMPLETED 24Aug 5, 2010Apr 19, 2013May 12, 202224 United States
NCT00877032Safety And Tolerability Study Of RN6G In Patients With Dry, Age-Related Macular DegenerationPHASE1 COMPLETED 57Apr 1, 2009Jul 1, 2011Mar 31, 201520 United States
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Study Endpoints
Primary Endpoints
Number of Participants With Toxicity or Intolerable Dose Criteria
Baseline up to Day 304/End of Treatment (ET)

The dose was considered intolerable if a participant developed either ocular toxicity or other toxicity as per Common Terminology Criteria for Adverse Events (CTCAE) or based on the investigator's discretion. Ocular toxicity included: Grade \>= 3 (retinopathy, retinal detachment, cataract formation, optic disk edema, keratitis, vitreous hemorrhage and uveitis) and acute vision loss of greater than 3 lines of vision up to and including 140 days after the first dose. Other toxicity included serious adverse event (SAE), Grade \>= 3 (increased liver transaminases, encephalopathy/leukoencephalopathy, diarrhea, enteritis or nausea, prolongation of QT interval \[Fridericia's correction\]), Grade \>=2 (central nervous system hemorrhage, decreased total leukocyte count, increased serum creatinine) and thrombocytopenia \<100\*10 9 /liter.

Number of Participants With Treatment Emergent Adverse Events (TEAEs) Categorized by Severity
Baseline up to Day 304/ET

AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent are events between first dose of study drug and up to Day 304/ET that were absent before treatment or that worsened relative to pretreatment state. AE was assessed according to severity; Grade 1 (mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated), Grade 2 (moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living \[ADL\]), Grade 3 (severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL), Grade 4 (life-threatening consequences; urgent intervention indicated) and Grade 5 (death related to AE).

Number of Participants With Treatment Emergent Adverse Events (TEAEs): All Causalities and TEAEs Categorized by Causal Relationship to Study Drug
Baseline up to Day 304/ET

All causalities AE was any untoward medical occurrence in participant who received study drug without regard to causal relationship. Drug-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent are events between first dose of study drug and up to Day 304/ET that were absent before treatment or that worsened relative to pretreatment state. All causalities and drug-related AEs reported wherein drug-related AEs were reported as ocular and non-ocular AEs. Ocular AEs were events which were localized in the ocular region and non-ocular AEs were systemic events which were not localized but occurred throughout the systemic circulation.

Number of Participants With Ocular Treatment Emergent Adverse Events (TEAEs) Categorized by Severity
Baseline up to Day 304/ET

AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent are events between first dose of study drug and up to Day 304/ET that were absent before treatment or that worsened relative to pretreatment state. Ocular AE were events which were localized in the ocular region and was assessed according to severity; Grade 1 (mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated), Grade 2 (moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL), Grade 3 (severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL), Grade 4 (life-threatening consequences; urgent intervention indicated) and Grade 5 (death related to AE).

Number of Participants With Ocular Treatment Emergent Adverse Events (TEAEs) Categorized by Causal Relationship to Study Drug
Baseline up to Day 304/ET

AE was any untoward medical occurrence in participant who received study drug without regard to causal relationship and drug-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent are events between first dose of study drug and up to Day 304/ET that were absent before treatment or that worsened relative to pretreatment state. Ocular AEs were events which were localized in the ocular region. Ocular AEs reported as related and non-related to study drug.

Number of Participants With Systemic Treatment Emergent Adverse Events (TEAEs) Categorized by Severity
Baseline up to Day 304/ET

AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent are events between first dose of study drug and up to Day 304/ET that were absent before treatment or that worsened relative to pretreatment state. Systemic AE were events which were not localized but occurred throughout the systemic circulation and was assessed according to severity; Grade 1 (mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated), Grade 2 (moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL), Grade 3 (severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL), Grade 4 (life-threatening consequences; urgent intervention indicated) and Grade 5 (death related to AE).

Number of Participants With Systemic Treatment Emergent Adverse Events (TEAEs) Categorized by Causal Relationship to Study Drug
Baseline up to Day 304/ET

AE was any untoward medical occurrence in participant who received study drug without regard to causal relationship and drug-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent are events between first dose of study drug and up to Day 304/ET that were absent before treatment or that worsened relative to pretreatment state. Systemic TEAEs were events which were not localized but occurred throughout the systemic circulation and reported as related and non-related to study drug.

Number of Participants With Positive Anti-Drug-Antibodies (ADA) and Neutralizing Antibodies (Nab)
Baseline up to Day 304/ET

The immunogenicity of RN6G (PF-04382923) in terms of producing an antidrug antibody (ADA) and neutralizing antibody response were assessed. Neutralizing antibody response were to be assess in participants with positive ADA samples.

Incidence and Severity of Ocular Adverse Events (AEs)
Baseline up to Day 168

AE: untoward medical occurrence in participant who received study drug without regard to causal relationship. Ocular AE was identified by spontaneous report or ocular examination: early treatment diabetic retinopathy study (ETDRS) best-corrected visual acuity (BCVA); low-luminance BCVA; pupillary light response, extra-ocular muscle movements, external examination of the eyelids and eyelashes, slit-lamp biomicroscopic examination (SLE) of all components of the anterior and posterior segments, intra-ocular pressure (IOP), and dilated ocular fundus examination of the vitreous and retina. AE was assessed according to severity; mild (did not interfere with participant's usual function), moderate (interfered to some extent with participant's usual function) and severe (interfered significantly with participant's usual function). Total number of participants with ocular (related to eye) AEs and severity was reported.

Incidence and Severity of Systemic Adverse Events (AEs)
Baseline up to Day 168

AE: untoward medical occurrence in participant who received study drug without regard to causal relationship. Systemic AEs was identified by spontaneous report or physical and neurological examinations changes in vital signs, clinical laboratory abnormalities, 12-lead electrocardiograms (ECG), brain magnetic resonance imaging (MRI). AE was assessed according to severity; mild (did not interfere with participant's usual function), moderate (interfered to some extent with participant's usual function) and severe (interfered significantly with participant's usual function). Total number of participants with systemic (all AEs including eye-related) AEs and severity was reported.

Secondary Endpoints
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of RN6G (PF-04382923)
Pre-dose: 0 hour on Day 1, 28, 56, 84,112,140; Post-dose: 1, 2, 4, 24, 168, 336 hours on Day 1 and 1, 2, 4, 24, 336, 672 hours on Day 140
Maximum Observed Plasma Concentration (Cmax) of RN6G (PF-04382923)
Pre-dose: 0 hour on Day 1, 28, 56, 84,112,140; Post-dose: 1, 2, 4, 24, 168, 336 hours on Day 1 and 1, 2, 4, 24, 336, 672, 1992, 3936 hours on Day 140
Minimum Observed Plasma Trough Concentration (Cmin) of RN6G (PF-04382923)
Pre-dose: 0 hour on Day 1, 28, 56, 84,112,140; Post-dose: 1, 2, 4, 24, 336, 672, 1992, 3936 hours on Day 140
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Study Design & Arms
AllocationRANDOMIZED
MaskingQUADRUPLE
ModelSEQUENTIAL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
Arm 1EXPERIMENTAL -
Interventions
NameTypeDescription
RN6GBIOLOGICALIntravenous, multiple dose, dose ranging from 5 mg/kg up to a maximum of 15 mg/kg
PlaceboBIOLOGICALIntravenous, multiple dose with experimental dose
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Eligibility Criteria
Age Range60 Years — 85 Years
SexALL
Healthy VolunteersNo
Study Sites24

Inclusion Criteria: * Be of non-child bearing potential * Diagnosis of dry AMD including uni- or multi-focal geographic atrophy without foveal involvement * BCVA of 20/50 or better in the study eye Exclusion Criteria: * Evidence of ocular disease other than advanced AMD or GA in the study eye * H...

Countries:United States
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