Age-Related Maculopathies, Age-Related Maculopathy, Eye Diseases, Macular Degeneration, Retinal Degeneration
Conditions
Keywords
Phase 1, Dry Age Related Macular Degeneration, RN6G
Brief summary
The purpose of this study is to determine the safety and tolerability of RN6G in patients with dry, age-related macular degeneration.
Interventions
BIOLOGICALPlacebo
intravenous, single dose with experimental dose.
BIOLOGICALRN6G
intravenous, single dose, dose ranging from 0.3mg/kg up to a maximum of 40 mg/kg.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Be of non-childbearing potential. * Diagnosis of dry AMD as defined by the Age-Related Eye Disease Study (AREDS, 2005), including uni- or multi-focal GA, without foveal involvement. * BCVA of 20/320 or better in the worst eye.
Exclusion criteria
* Diagnosis of exudative (wet) AMD, with subretinal or choroidal neovascular lesions. * Diagnosis or history of Alzheimer's disease, dementia or neurodegenerative disorders. * Diagnosis or recent history of clinically significant cerebrovascular disease. * Uncontrolled hypertension. * Uncontrolled Type 1 or Type 2 diabetes mellitus.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of RN6G | Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168 | AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t). Participants who received RN6G were reported. |
| Maximum Observed Plasma Concentration (Cmax) of RN6G | Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168 | Participants who received RN6G were reported. |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of RN6G | Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168 | Participants who received RN6G were reported. |
| Volume of Distribution (Vd) of RN6G | Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168 | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Participants who received RN6G were reported and volume was measured as volume/kg of body weight. |
| Clearance (CL) of RN6G | Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168 | CL is a quantitative measure of the rate at which a drug substance is removed from the body. Participants who received RN6G were reported and clearance was measured as mL/hr/kg of body weight. |
| Number of Participants With Anti-Drug Anti-body | Baseline up to Day 168 | Participants tested positive for anti-drug anti-body on at least one or more occasions were reported. |
| Plasma Terminal Half-life (t1/2) of RN6G | Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168 | Plasma terminal half-life is the time measured for the plasma concentration to decrease by one half. Participants who received RN6G were reported. |
| Maximum Observed Plasma Concentration (Cmax) of Amyloid (A) Beta(1-X) | Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168 | — |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of Amyloid (A) Beta(1-X) | Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168 | — |
| Area Under the Curve From Time Zero to Day 165 [AUC (0-165d)] of Amyloid (A) Beta(1-X) | Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 165 | AUC (0-165d)= Area under the plasma concentration versus time curve from time zero (pre-dose) to Day 165. |
| Mean Residence Time (MRT) of RN6G | Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168 | MRT was calculated as area under the moment curve from time 0 to extrapolated infinite time (AUMC\[0 to inf\])/area under the concentration effect curve from time 0 to extrapolated infinite time (AUC\[0 to inf\]). AUMC (0 to inf)= area under the moment curve from 0 to time t (AUMC 0-t) + \[(Ct\*tlast )/lamdaz \] + \[Ct/(lamdaz )\^2 \] where Ct= last measurable concentration, tlast= last measurable time, lamdaz= apparent terminal elimination rate constant. Participants who received RN6G were reported. |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of RN6G | Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168 | AUC (0 - inf) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - inf). It is obtained from AUC (0 - t) plus AUC (t - inf). Participants who received RN6G were reported. |
Countries
United States
Participant flow
Pre-assignment details
From a given cohort, no more than 3 participants received treatment on Day 1, the remaining participants in the respective cohort received treatment at least 24 hours thereafter. All the remaining participants were treated on same day, if required, as per site scheduling.
Participants by arm
| Arm | Count |
|---|---|
| RN6G 0.3 mg/kg Single intravenous infusion dose of RN6G 0.3 milligram per kilogram (mg/kg) of body weight over 120 to 160 minutes on Day 1. | 6 |
| RN6G 1 mg/kg Single intravenous infusion dose of RN6G 1 mg/kg of body weight over 120 to 160 minutes on Day 1. | 6 |
| RN6G 3 mg/kg Single intravenous infusion dose of RN6G 3 mg/kg of body weight over 120 to 160 minutes on Day 1. | 6 |
| RN6G 10 mg/kg Single intravenous infusion dose of RN6G 10 mg/kg of body weight over 120 to 160 minutes on Day 1. | 6 |
| RN6G 20 mg/kg Single intravenous infusion dose of RN6G 20 mg/kg of body weight over 120 to 160 minutes on Day 1. | 6 |
| RN6G 40 mg/kg Single intravenous infusion dose of RN6G 40 mg/kg of body weight over 120 to 160 minutes on Day 1. | 6 |
| Placebo Single intravenous infusion dose of placebo matched to RN6G on Day 1. | 18 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Did not meet entrance criteria | 0 | 0 | 0 | 1 | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | RN6G 0.3 mg/kg | RN6G 1 mg/kg | RN6G 3 mg/kg | RN6G 10 mg/kg | RN6G 20 mg/kg | RN6G 40 mg/kg | Placebo | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 68.2 years STANDARD_DEVIATION 11.1 | 70.2 years STANDARD_DEVIATION 9.9 | 65.5 years STANDARD_DEVIATION 10.4 | 69.2 years STANDARD_DEVIATION 3.7 | 67.8 years STANDARD_DEVIATION 7.5 | 65.0 years STANDARD_DEVIATION 6.5 | 67.4 years STANDARD_DEVIATION 8.2 | 67.6 years STANDARD_DEVIATION 8.1 |
| Sex: Female, Male Female | 4 Participants | 2 Participants | 5 Participants | 2 Participants | 5 Participants | 4 Participants | 14 Participants | 36 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 1 Participants | 4 Participants | 1 Participants | 2 Participants | 4 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 6 | 5 / 6 | 5 / 6 | 4 / 6 | 6 / 6 | 6 / 6 | 15 / 18 |
| serious Total, serious adverse events | 0 / 6 | 1 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 18 |
Outcome results
Primary
Incidence and Severity of Ocular Adverse Events (AEs)
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.
Time frame: Baseline up to Day 168
Population: Safety analysis population included all participants who received any amount of the single dose of either study drug or placebo.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RN6G 0.3 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Severe ocular AEs: right eye | 0 participants |
| RN6G 0.3 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Severe ocular AEs: left eye | 0 participants |
| RN6G 0.3 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Mild ocular AEs: both eyes | 0 participants |
| RN6G 0.3 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Moderate ocular AEs: left eye | 1 participants |
| RN6G 0.3 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Mild ocular AEs: right eye | 1 participants |
| RN6G 0.3 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Moderate ocular AEs: right eye | 1 participants |
| RN6G 0.3 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Moderate ocular AEs: both eyes | 0 participants |
| RN6G 0.3 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Ocular AEs | 1 participants |
| RN6G 0.3 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Severe ocular AEs: both eyes | 0 participants |
| RN6G 0.3 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Mild ocular AEs: left eye | 1 participants |
| RN6G 1 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Severe ocular AEs: both eyes | 0 participants |
| RN6G 1 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Severe ocular AEs: right eye | 0 participants |
| RN6G 1 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Ocular AEs | 3 participants |
| RN6G 1 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Severe ocular AEs: left eye | 0 participants |
| RN6G 1 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Mild ocular AEs: right eye | 1 participants |
| RN6G 1 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Mild ocular AEs: left eye | 2 participants |
| RN6G 1 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Mild ocular AEs: both eyes | 1 participants |
| RN6G 1 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Moderate ocular AEs: both eyes | 0 participants |
| RN6G 1 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Moderate ocular AEs: left eye | 0 participants |
| RN6G 1 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Moderate ocular AEs: right eye | 1 participants |
| RN6G 3 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Severe ocular AEs: both eyes | 0 participants |
| RN6G 3 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Moderate ocular AEs: right eye | 1 participants |
| RN6G 3 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Moderate ocular AEs: left eye | 0 participants |
| RN6G 3 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Mild ocular AEs: right eye | 1 participants |
| RN6G 3 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Mild ocular AEs: left eye | 1 participants |
| RN6G 3 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Ocular AEs | 2 participants |
| RN6G 3 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Severe ocular AEs: left eye | 0 participants |
| RN6G 3 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Mild ocular AEs: both eyes | 1 participants |
| RN6G 3 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Moderate ocular AEs: both eyes | 0 participants |
| RN6G 3 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Severe ocular AEs: right eye | 0 participants |
| RN6G 10 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Mild ocular AEs: left eye | 0 participants |
| RN6G 10 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Moderate ocular AEs: both eyes | 0 participants |
| RN6G 10 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Ocular AEs | 1 participants |
| RN6G 10 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Severe ocular AEs: both eyes | 0 participants |
| RN6G 10 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Mild ocular AEs: right eye | 0 participants |
| RN6G 10 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Severe ocular AEs: left eye | 0 participants |
| RN6G 10 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Moderate ocular AEs: left eye | 0 participants |
| RN6G 10 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Mild ocular AEs: both eyes | 1 participants |
| RN6G 10 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Severe ocular AEs: right eye | 0 participants |
| RN6G 10 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Moderate ocular AEs: right eye | 0 participants |
| RN6G 20 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Moderate ocular AEs: right eye | 1 participants |
| RN6G 20 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Mild ocular AEs: both eyes | 2 participants |
| RN6G 20 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Ocular AEs | 4 participants |
| RN6G 20 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Mild ocular AEs: right eye | 1 participants |
| RN6G 20 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Mild ocular AEs: left eye | 1 participants |
| RN6G 20 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Moderate ocular AEs: left eye | 2 participants |
| RN6G 20 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Moderate ocular AEs: both eyes | 0 participants |
| RN6G 20 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Severe ocular AEs: right eye | 0 participants |
| RN6G 20 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Severe ocular AEs: left eye | 0 participants |
| RN6G 20 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Severe ocular AEs: both eyes | 0 participants |
| RN6G 40 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Moderate ocular AEs: both eyes | 0 participants |
| RN6G 40 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Moderate ocular AEs: right eye | 0 participants |
| RN6G 40 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Mild ocular AEs: both eyes | 1 participants |
| RN6G 40 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Ocular AEs | 3 participants |
| RN6G 40 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Severe ocular AEs: right eye | 0 participants |
| RN6G 40 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Mild ocular AEs: left eye | 2 participants |
| RN6G 40 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Severe ocular AEs: both eyes | 0 participants |
| RN6G 40 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Severe ocular AEs: left eye | 0 participants |
| RN6G 40 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Mild ocular AEs: right eye | 0 participants |
| RN6G 40 mg/kg | Incidence and Severity of Ocular Adverse Events (AEs) | Moderate ocular AEs: left eye | 0 participants |
| Placebo | Incidence and Severity of Ocular Adverse Events (AEs) | Severe ocular AEs: both eyes | 0 participants |
| Placebo | Incidence and Severity of Ocular Adverse Events (AEs) | Moderate ocular AEs: both eyes | 0 participants |
| Placebo | Incidence and Severity of Ocular Adverse Events (AEs) | Mild ocular AEs: right eye | 2 participants |
| Placebo | Incidence and Severity of Ocular Adverse Events (AEs) | Mild ocular AEs: both eyes | 3 participants |
| Placebo | Incidence and Severity of Ocular Adverse Events (AEs) | Moderate ocular AEs: right eye | 1 participants |
| Placebo | Incidence and Severity of Ocular Adverse Events (AEs) | Moderate ocular AEs: left eye | 1 participants |
| Placebo | Incidence and Severity of Ocular Adverse Events (AEs) | Severe ocular AEs: left eye | 0 participants |
| Placebo | Incidence and Severity of Ocular Adverse Events (AEs) | Severe ocular AEs: right eye | 0 participants |
| Placebo | Incidence and Severity of Ocular Adverse Events (AEs) | Mild ocular AEs: left eye | 2 participants |
| Placebo | Incidence and Severity of Ocular Adverse Events (AEs) | Ocular AEs | 6 participants |
Primary
Incidence and Severity of Systemic Adverse Events (AEs)
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.
Time frame: Baseline up to Day 168
Population: Safety analysis population included all participants who received any amount of the single dose of either study drug or placebo.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RN6G 0.3 mg/kg | Incidence and Severity of Systemic Adverse Events (AEs) | Systemic AEs | 4 participants |
| RN6G 0.3 mg/kg | Incidence and Severity of Systemic Adverse Events (AEs) | Severe systemic AEs | 0 participants |
| RN6G 0.3 mg/kg | Incidence and Severity of Systemic Adverse Events (AEs) | Moderate systemic AEs | 1 participants |
| RN6G 0.3 mg/kg | Incidence and Severity of Systemic Adverse Events (AEs) | Mild systemic AEs | 4 participants |
| RN6G 1 mg/kg | Incidence and Severity of Systemic Adverse Events (AEs) | Mild systemic AEs | 5 participants |
| RN6G 1 mg/kg | Incidence and Severity of Systemic Adverse Events (AEs) | Severe systemic AEs | 0 participants |
| RN6G 1 mg/kg | Incidence and Severity of Systemic Adverse Events (AEs) | Systemic AEs | 5 participants |
| RN6G 1 mg/kg | Incidence and Severity of Systemic Adverse Events (AEs) | Moderate systemic AEs | 2 participants |
| RN6G 3 mg/kg | Incidence and Severity of Systemic Adverse Events (AEs) | Severe systemic AEs | 0 participants |
| RN6G 3 mg/kg | Incidence and Severity of Systemic Adverse Events (AEs) | Mild systemic AEs | 5 participants |
| RN6G 3 mg/kg | Incidence and Severity of Systemic Adverse Events (AEs) | Moderate systemic AEs | 2 participants |
| RN6G 3 mg/kg | Incidence and Severity of Systemic Adverse Events (AEs) | Systemic AEs | 5 participants |
| RN6G 10 mg/kg | Incidence and Severity of Systemic Adverse Events (AEs) | Mild systemic AEs | 2 participants |
| RN6G 10 mg/kg | Incidence and Severity of Systemic Adverse Events (AEs) | Systemic AEs | 4 participants |
| RN6G 10 mg/kg | Incidence and Severity of Systemic Adverse Events (AEs) | Moderate systemic AEs | 2 participants |
| RN6G 10 mg/kg | Incidence and Severity of Systemic Adverse Events (AEs) | Severe systemic AEs | 0 participants |
| RN6G 20 mg/kg | Incidence and Severity of Systemic Adverse Events (AEs) | Severe systemic AEs | 0 participants |
| RN6G 20 mg/kg | Incidence and Severity of Systemic Adverse Events (AEs) | Mild systemic AEs | 6 participants |
| RN6G 20 mg/kg | Incidence and Severity of Systemic Adverse Events (AEs) | Systemic AEs | 6 participants |
| RN6G 20 mg/kg | Incidence and Severity of Systemic Adverse Events (AEs) | Moderate systemic AEs | 3 participants |
| RN6G 40 mg/kg | Incidence and Severity of Systemic Adverse Events (AEs) | Systemic AEs | 6 participants |
| RN6G 40 mg/kg | Incidence and Severity of Systemic Adverse Events (AEs) | Moderate systemic AEs | 2 participants |
| RN6G 40 mg/kg | Incidence and Severity of Systemic Adverse Events (AEs) | Mild systemic AEs | 5 participants |
| RN6G 40 mg/kg | Incidence and Severity of Systemic Adverse Events (AEs) | Severe systemic AEs | 0 participants |
| Placebo | Incidence and Severity of Systemic Adverse Events (AEs) | Severe systemic AEs | 0 participants |
| Placebo | Incidence and Severity of Systemic Adverse Events (AEs) | Systemic AEs | 15 participants |
| Placebo | Incidence and Severity of Systemic Adverse Events (AEs) | Mild systemic AEs | 15 participants |
| Placebo | Incidence and Severity of Systemic Adverse Events (AEs) | Moderate systemic AEs | 7 participants |
Secondary
Area Under the Curve From Time Zero to Day 165 [AUC (0-165d)] of Amyloid (A) Beta(1-X)
AUC (0-165d)= Area under the plasma concentration versus time curve from time zero (pre-dose) to Day 165.
Time frame: Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 165
Population: PD analysis population included all participants who received any amount of the single dose of either study drug or placebo.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RN6G 0.3 mg/kg | Area Under the Curve From Time Zero to Day 165 [AUC (0-165d)] of Amyloid (A) Beta(1-X) | 2512 nanogram*hr/mL (ng*hr/mL) | Standard Deviation 752 |
| RN6G 1 mg/kg | Area Under the Curve From Time Zero to Day 165 [AUC (0-165d)] of Amyloid (A) Beta(1-X) | 4512 nanogram*hr/mL (ng*hr/mL) | Standard Deviation 1780 |
| RN6G 3 mg/kg | Area Under the Curve From Time Zero to Day 165 [AUC (0-165d)] of Amyloid (A) Beta(1-X) | 12041 nanogram*hr/mL (ng*hr/mL) | Standard Deviation 2553 |
| RN6G 10 mg/kg | Area Under the Curve From Time Zero to Day 165 [AUC (0-165d)] of Amyloid (A) Beta(1-X) | 46852 nanogram*hr/mL (ng*hr/mL) | Standard Deviation 12562 |
| RN6G 20 mg/kg | Area Under the Curve From Time Zero to Day 165 [AUC (0-165d)] of Amyloid (A) Beta(1-X) | 85441 nanogram*hr/mL (ng*hr/mL) | Standard Deviation 22829 |
| RN6G 40 mg/kg | Area Under the Curve From Time Zero to Day 165 [AUC (0-165d)] of Amyloid (A) Beta(1-X) | 113547 nanogram*hr/mL (ng*hr/mL) | Standard Deviation 19280 |
| Placebo | Area Under the Curve From Time Zero to Day 165 [AUC (0-165d)] of Amyloid (A) Beta(1-X) | 1572 nanogram*hr/mL (ng*hr/mL) | Standard Deviation 392 |
Secondary
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of RN6G
AUC (0 - inf) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - inf). It is obtained from AUC (0 - t) plus AUC (t - inf). Participants who received RN6G were reported.
Time frame: Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168
Population: Pharmacokinetic (PK) analysis population included all participants who received any amount of the single dose of RN6G. Here N (number of participants analyzed) signifies participants evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RN6G 0.3 mg/kg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of RN6G | 1003 microgram*hour/milliliter (mcg*hr/mL) | Standard Deviation 399 |
| RN6G 1 mg/kg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of RN6G | 4516 microgram*hour/milliliter (mcg*hr/mL) | Standard Deviation 627 |
| RN6G 3 mg/kg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of RN6G | 19591 microgram*hour/milliliter (mcg*hr/mL) | Standard Deviation 3657 |
| RN6G 10 mg/kg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of RN6G | 76987 microgram*hour/milliliter (mcg*hr/mL) | Standard Deviation 18255 |
| RN6G 20 mg/kg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of RN6G | 163049 microgram*hour/milliliter (mcg*hr/mL) | Standard Deviation 57995 |
| RN6G 40 mg/kg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of RN6G | 486191 microgram*hour/milliliter (mcg*hr/mL) | Standard Deviation 64822 |
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of RN6G
AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t). Participants who received RN6G were reported.
Time frame: Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168
Population: PK analysis population included all participants who received any amount of the single dose of RN6G.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RN6G 0.3 mg/kg | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of RN6G | 836 mcg*hr/mL | Standard Deviation 326 |
| RN6G 1 mg/kg | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of RN6G | 3990 mcg*hr/mL | Standard Deviation 593 |
| RN6G 3 mg/kg | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of RN6G | 17878 mcg*hr/mL | Standard Deviation 3395 |
| RN6G 10 mg/kg | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of RN6G | 72792 mcg*hr/mL | Standard Deviation 15929 |
| RN6G 20 mg/kg | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of RN6G | 155377 mcg*hr/mL | Standard Deviation 52319 |
| RN6G 40 mg/kg | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of RN6G | 472239 mcg*hr/mL | Standard Deviation 59181 |
Secondary
Clearance (CL) of RN6G
CL is a quantitative measure of the rate at which a drug substance is removed from the body. Participants who received RN6G were reported and clearance was measured as mL/hr/kg of body weight.
Time frame: Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168
Population: PK analysis population included all participants who received any amount of the single dose of RN6G. Here N (number of participants analyzed) signifies participants evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RN6G 0.3 mg/kg | Clearance (CL) of RN6G | 0.336 mL/hr/kg | Standard Deviation 0.117 |
| RN6G 1 mg/kg | Clearance (CL) of RN6G | 0.225 mL/hr/kg | Standard Deviation 0.0287 |
| RN6G 3 mg/kg | Clearance (CL) of RN6G | 0.158 mL/hr/kg | Standard Deviation 0.031 |
| RN6G 10 mg/kg | Clearance (CL) of RN6G | 0.137 mL/hr/kg | Standard Deviation 0.037 |
| RN6G 20 mg/kg | Clearance (CL) of RN6G | 0.134 mL/hr/kg | Standard Deviation 0.04 |
| RN6G 40 mg/kg | Clearance (CL) of RN6G | 0.0835 mL/hr/kg | Standard Deviation 0.0115 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Amyloid (A) Beta(1-X)
Time frame: Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168
Population: Pharmacodynamic (PD) analysis population included all participants who received any amount of the single dose of either study drug or placebo.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RN6G 0.3 mg/kg | Maximum Observed Plasma Concentration (Cmax) of Amyloid (A) Beta(1-X) | 3607 picogram/milliliter (pg/mL) | Standard Deviation 1517 |
| RN6G 1 mg/kg | Maximum Observed Plasma Concentration (Cmax) of Amyloid (A) Beta(1-X) | 10318 picogram/milliliter (pg/mL) | Standard Deviation 3312 |
| RN6G 3 mg/kg | Maximum Observed Plasma Concentration (Cmax) of Amyloid (A) Beta(1-X) | 21267 picogram/milliliter (pg/mL) | Standard Deviation 2836 |
| RN6G 10 mg/kg | Maximum Observed Plasma Concentration (Cmax) of Amyloid (A) Beta(1-X) | 59000 picogram/milliliter (pg/mL) | Standard Deviation 14599 |
| RN6G 20 mg/kg | Maximum Observed Plasma Concentration (Cmax) of Amyloid (A) Beta(1-X) | 70967 picogram/milliliter (pg/mL) | Standard Deviation 10265 |
| RN6G 40 mg/kg | Maximum Observed Plasma Concentration (Cmax) of Amyloid (A) Beta(1-X) | 75700 picogram/milliliter (pg/mL) | Standard Deviation 11773 |
| Placebo | Maximum Observed Plasma Concentration (Cmax) of Amyloid (A) Beta(1-X) | 533 picogram/milliliter (pg/mL) | Standard Deviation 177 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of RN6G
Participants who received RN6G were reported.
Time frame: Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168
Population: PK analysis population included all participants who received any amount of the single dose of RN6G.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RN6G 0.3 mg/kg | Maximum Observed Plasma Concentration (Cmax) of RN6G | 4.70 mcg/mL | Standard Deviation 0.87 |
| RN6G 1 mg/kg | Maximum Observed Plasma Concentration (Cmax) of RN6G | 23.1 mcg/mL | Standard Deviation 2.9 |
| RN6G 3 mg/kg | Maximum Observed Plasma Concentration (Cmax) of RN6G | 75.2 mcg/mL | Standard Deviation 9.3 |
| RN6G 10 mg/kg | Maximum Observed Plasma Concentration (Cmax) of RN6G | 286 mcg/mL | Standard Deviation 58 |
| RN6G 20 mg/kg | Maximum Observed Plasma Concentration (Cmax) of RN6G | 435 mcg/mL | Standard Deviation 87 |
| RN6G 40 mg/kg | Maximum Observed Plasma Concentration (Cmax) of RN6G | 1245 mcg/mL | Standard Deviation 142 |
Secondary
Mean Residence Time (MRT) of RN6G
MRT was calculated as area under the moment curve from time 0 to extrapolated infinite time (AUMC\[0 to inf\])/area under the concentration effect curve from time 0 to extrapolated infinite time (AUC\[0 to inf\]). AUMC (0 to inf)= area under the moment curve from 0 to time t (AUMC 0-t) + \[(Ct\*tlast )/lamdaz \] + \[Ct/(lamdaz )\^2 \] where Ct= last measurable concentration, tlast= last measurable time, lamdaz= apparent terminal elimination rate constant. Participants who received RN6G were reported.
Time frame: Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168
Population: PK analysis population included all participants who received any amount of the single dose of RN6G. Here N (number of participants analyzed) signifies participants evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RN6G 0.3 mg/kg | Mean Residence Time (MRT) of RN6G | 36.2 days | Standard Deviation 19.7 |
| RN6G 1 mg/kg | Mean Residence Time (MRT) of RN6G | 57.3 days | Standard Deviation 16.8 |
| RN6G 3 mg/kg | Mean Residence Time (MRT) of RN6G | 51.5 days | Standard Deviation 5.8 |
| RN6G 10 mg/kg | Mean Residence Time (MRT) of RN6G | 37.7 days | Standard Deviation 8.3 |
| RN6G 20 mg/kg | Mean Residence Time (MRT) of RN6G | 41.9 days | Standard Deviation 10 |
| RN6G 40 mg/kg | Mean Residence Time (MRT) of RN6G | 38.0 days | Standard Deviation 6.8 |
Secondary
Number of Participants With Anti-Drug Anti-body
Participants tested positive for anti-drug anti-body on at least one or more occasions were reported.
Time frame: Baseline up to Day 168
Population: Safety analysis population included all participants who received any amount of the single dose of either study drug or placebo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RN6G 0.3 mg/kg | Number of Participants With Anti-Drug Anti-body | 2 participants |
| RN6G 1 mg/kg | Number of Participants With Anti-Drug Anti-body | 1 participants |
| RN6G 3 mg/kg | Number of Participants With Anti-Drug Anti-body | 0 participants |
| RN6G 10 mg/kg | Number of Participants With Anti-Drug Anti-body | 2 participants |
| RN6G 20 mg/kg | Number of Participants With Anti-Drug Anti-body | 1 participants |
| RN6G 40 mg/kg | Number of Participants With Anti-Drug Anti-body | 2 participants |
| Placebo | Number of Participants With Anti-Drug Anti-body | 0 participants |
Secondary
Plasma Terminal Half-life (t1/2) of RN6G
Plasma terminal half-life is the time measured for the plasma concentration to decrease by one half. Participants who received RN6G were reported.
Time frame: Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168
Population: PK analysis population included all participants who received any amount of the single dose of RN6G. Here N (number of participants analyzed) signifies participants evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RN6G 0.3 mg/kg | Plasma Terminal Half-life (t1/2) of RN6G | 37.5 days | Standard Deviation 20.1 |
| RN6G 1 mg/kg | Plasma Terminal Half-life (t1/2) of RN6G | 71.5 days | Standard Deviation 20.5 |
| RN6G 3 mg/kg | Plasma Terminal Half-life (t1/2) of RN6G | 61.4 days | Standard Deviation 5.8 |
| RN6G 10 mg/kg | Plasma Terminal Half-life (t1/2) of RN6G | 50.1 days | Standard Deviation 9.4 |
| RN6G 20 mg/kg | Plasma Terminal Half-life (t1/2) of RN6G | 43.3 days | Standard Deviation 6.7 |
| RN6G 40 mg/kg | Plasma Terminal Half-life (t1/2) of RN6G | 34.2 days | Standard Deviation 5.1 |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Amyloid (A) Beta(1-X)
Time frame: Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168
Population: PD analysis population included all participants who received any amount of the single dose of either study drug or placebo.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| RN6G 0.3 mg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Amyloid (A) Beta(1-X) | 14.3 hours |
| RN6G 1 mg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Amyloid (A) Beta(1-X) | 26.0 hours |
| RN6G 3 mg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Amyloid (A) Beta(1-X) | 26.1 hours |
| RN6G 10 mg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Amyloid (A) Beta(1-X) | 160 hours |
| RN6G 20 mg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Amyloid (A) Beta(1-X) | 317 hours |
| RN6G 40 mg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Amyloid (A) Beta(1-X) | 402 hours |
| Placebo | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Amyloid (A) Beta(1-X) | 14.3 hours |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of RN6G
Participants who received RN6G were reported.
Time frame: Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168
Population: PK analysis population included all participants who received any amount of the single dose of RN6G.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| RN6G 0.3 mg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of RN6G | 2.1 hours |
| RN6G 1 mg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of RN6G | 2.1 hours |
| RN6G 3 mg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of RN6G | 2.0 hours |
| RN6G 10 mg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of RN6G | 4.5 hours |
| RN6G 20 mg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of RN6G | 2.5 hours |
| RN6G 40 mg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of RN6G | 2.1 hours |
Secondary
Volume of Distribution (Vd) of RN6G
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Participants who received RN6G were reported and volume was measured as volume/kg of body weight.
Time frame: Pre-dose on Day 1; 1 hour (hr) during infusion on Day 1; 0, 1, 4, 8, 12 hrs post-dose on Day 1; Day 2, 7, 14, 21, 28, 42, 56, 84, 168
Population: PK analysis population included all participants who received any amount of the single dose of RN6G. Here N (number of participants analyzed) signifies participants evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RN6G 0.3 mg/kg | Volume of Distribution (Vd) of RN6G | 384 mL/kilogram (mL/kg) | Standard Deviation 86.8 |
| RN6G 1 mg/kg | Volume of Distribution (Vd) of RN6G | 555 mL/kilogram (mL/kg) | Standard Deviation 180 |
| RN6G 3 mg/kg | Volume of Distribution (Vd) of RN6G | 336 mL/kilogram (mL/kg) | Standard Deviation 74.8 |
| RN6G 10 mg/kg | Volume of Distribution (Vd) of RN6G | 230 mL/kilogram (mL/kg) | Standard Deviation 39.5 |
| RN6G 20 mg/kg | Volume of Distribution (Vd) of RN6G | 198 mL/kilogram (mL/kg) | Standard Deviation 57.1 |
| RN6G 40 mg/kg | Volume of Distribution (Vd) of RN6G | 98.0 mL/kilogram (mL/kg) | Standard Deviation 12.1 |