Multiple Sclerosis
Conditions
Keywords
Multiple Sclerosis, MRI
Brief summary
PF-06342674 (RN168), being developed for the treatment of multiple sclerosis (MS), is an antibody that binds to and inhibits the human interleukin-7 receptor, a component potentially involved in MS. PF-06342674 (RN168) is expected to play a role in slowing down the progression of the disease.
Interventions
BIOLOGICALPF-06342674 0.25 mg/kg
Bi-Weekly Subcutaneous Injections X 6
BIOLOGICALPlacebo
Bi-Weekly Subcutaneous Injections X 6
BIOLOGICALPF-06342674 1.5 mg/kg
Bi-Weekly Subcutaneous Injections X 6
BIOLOGICALPF-06342674 6.0 mg/kg
Bi-Weekly Subcutaneous Injections X 6
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Women and men aged 18-55 yrs. * Confirmed diagnosis of Multiple Sclerosis (MS) according to the 2010 revision of the McDonald Criteria. * Expanded Disability Status Scale (EDSS) between 0-5, inclusive.
Exclusion criteria
* Relapse episode of MS within 2 weeks of enrollment. * Primary progressive MS without a relapsing component. * Intolerant or unwilling to undergo MRI scanning. Treatment with disease modifying agents up to 6 weeks prior to enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinical Laboratory Abnormalities | Baseline through Day 127/Early Termination | Number of participants with laboratory test abnormalities without regard to baseline abnormality. Laboratory test parameters included hematology, liver function, renal function, electrolytes, hormones, clinical chemistry, and urinalysis (dipstick and microscopy). Abnormal laboratory findings included: lymphocytes (absolute) less than (\<)0.8 x lower limit of normal (LLN); urine blood/hemoglobin (qualitative) more than or equal to (\>=)1; urine nitrite \>=1; urine leukocyte esterase \>=1; urine red blood cell (RBC) \>=20/high-power field (HPF). |
| Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Withdrawals Due to AEs | Baseline through Day 127/Early Termination | An AE was any untoward medical occurrence in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs are events between first dose of study drug and up to Day 127/Early Termination that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs. |
| Number of Treatment-Emergent AEs and SAEs by Severity | Baseline through Day 127/Early Termination | AE severity was graded as mild, moderate, or severe. Mild AEs do not interfere with the participant's usual function. Moderate AEs interfere to some extent with the participant's usual function. Severe AEs interfere significantly with the participant's usual function. |
| Number of Participants With Confirmed Positive Anti-Drug Antibodies (ADAs) | Baseline, and Days 15, 29, 57, 85 and Day 127/Early Termination | Assays for the determination of a positive immune response was performed. An antibody immune response was defined as a confirmed post-treatment positive enzyme-linked immunosorbent assay (ELISA) result in combination with a negative baseline sample ELISA result. ADA positive was defined as ADA titer (ie, the reciprocal of the highest dilution that gives a value equivalent to the cut point of the assay) \>=4.32. |
| Number of Participants With Clinically Significant Changes in Vital Signs | Baseline through Day 127/Early Termination | Categorical summarization criteria in vital signs included: supine systolic blood pressure (SBP) of \<90 millimeters of mercury (mm Hg) or change in supine SBP of \>=30 mm Hg; supine diastolic blood pressure (DBP) of \<50 mm Hg or change in supine DBP of \>=20 mm Hg; supine pulse rate of \<40 or more than (\>)120 beats per minute (bpm). |
| Number of Participants With Abnormal Electrocardiogram (ECG) | Baseline through Day 127/Early Termination | Criteria for potential clinical concern in ECG parameters: The maximum of the beginning of the Q wave to the end of the T wave corresponding to electrical systole (QT) interval corrected using the Fridericia formula (QTcF) \>=450 milliseconds (msec), maximum QTcF interval change from baseline in range of 30 to \<60 msec and \>=60 msec. |
Secondary
| Measure | Time frame |
|---|---|
| Concentration of PF-06342674 | Baseline through Day 127/Early Termination |
Countries
United States
Participant flow
Recruitment details
This study was a Phase 1b, randomized, multi-center, double-blind, sponsor-open, placebo controlled study to evaluate multiple ascending doses of PF-06342674 in participants with Multiple Sclerosis (MS). Up to 60 participants were planned to be enrolled. However, only 4 participants were randomized due to the early termination of the study.
Pre-assignment details
Participants were screened within 45 days prior to the first administration of the study drug to confirm that they met the participant inclusion criteria for the study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo SC every other week during an 85-day treatment period. | 1 |
| PF-06342674 0.25 mg/kg Participants received PF-06342674 0.25 mg/kg SC every other week during an 85-day treatment period. | 3 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | At the discretion of the investigator | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo | PF-06342674 0.25 mg/kg | Total |
|---|---|---|---|
| Age, Continuous | 33 years STANDARD_DEVIATION 0 | 45.3 years STANDARD_DEVIATION 14.2 | 42.3 years STANDARD_DEVIATION 13.1 |
| Gender Female | 1 Participants | 3 Participants | 4 Participants |
| Gender Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 1 | 3 / 3 |
| serious Total, serious adverse events | 0 / 1 | 0 / 3 |
Outcome results
Primary
Number of Participants With Abnormal Electrocardiogram (ECG)
Criteria for potential clinical concern in ECG parameters: The maximum of the beginning of the Q wave to the end of the T wave corresponding to electrical systole (QT) interval corrected using the Fridericia formula (QTcF) \>=450 milliseconds (msec), maximum QTcF interval change from baseline in range of 30 to \<60 msec and \>=60 msec.
Time frame: Baseline through Day 127/Early Termination
Population: The safety analysis population consists of all participants who received at least 1 dose of study drug. The QTcF interval of the participant in the placebo arm was in this range of 450 to \<480 msec at Baseline. This participant experienced a decrease in QTcF of 30 to \<60 msec on Day 30, which then returned to baseline levels on Day 57.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) | QTcF Interval 450-<480 msec | 1 participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) | QTcF Interval >=480 msec | 0 participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) | QTcF Interval 30-<60 msec Increase From Baseline | 0 participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) | QTcF Interval >=60 msec Increase From Baseline | 0 participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) | QTcF Interval 30-<60 msec Decrease From Baseline | 1 participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) | QTcF Interval >=60 msec Decrease From Baseline | 0 participants |
| PF-06342674 0.25 mg/kg | Number of Participants With Abnormal Electrocardiogram (ECG) | QTcF Interval 30-<60 msec Decrease From Baseline | 0 participants |
| PF-06342674 0.25 mg/kg | Number of Participants With Abnormal Electrocardiogram (ECG) | QTcF Interval 450-<480 msec | 0 participants |
| PF-06342674 0.25 mg/kg | Number of Participants With Abnormal Electrocardiogram (ECG) | QTcF Interval >=60 msec Increase From Baseline | 0 participants |
| PF-06342674 0.25 mg/kg | Number of Participants With Abnormal Electrocardiogram (ECG) | QTcF Interval >=480 msec | 0 participants |
| PF-06342674 0.25 mg/kg | Number of Participants With Abnormal Electrocardiogram (ECG) | QTcF Interval >=60 msec Decrease From Baseline | 0 participants |
| PF-06342674 0.25 mg/kg | Number of Participants With Abnormal Electrocardiogram (ECG) | QTcF Interval 30-<60 msec Increase From Baseline | 0 participants |
Primary
Number of Participants With Clinical Laboratory Abnormalities
Number of participants with laboratory test abnormalities without regard to baseline abnormality. Laboratory test parameters included hematology, liver function, renal function, electrolytes, hormones, clinical chemistry, and urinalysis (dipstick and microscopy). Abnormal laboratory findings included: lymphocytes (absolute) less than (\<)0.8 x lower limit of normal (LLN); urine blood/hemoglobin (qualitative) more than or equal to (\>=)1; urine nitrite \>=1; urine leukocyte esterase \>=1; urine red blood cell (RBC) \>=20/high-power field (HPF).
Time frame: Baseline through Day 127/Early Termination
Population: The safety analysis population consists of all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Clinical Laboratory Abnormalities | 0 participants |
| PF-06342674 0.25 mg/kg | Number of Participants With Clinical Laboratory Abnormalities | 3 participants |
Primary
Number of Participants With Clinically Significant Changes in Vital Signs
Categorical summarization criteria in vital signs included: supine systolic blood pressure (SBP) of \<90 millimeters of mercury (mm Hg) or change in supine SBP of \>=30 mm Hg; supine diastolic blood pressure (DBP) of \<50 mm Hg or change in supine DBP of \>=20 mm Hg; supine pulse rate of \<40 or more than (\>)120 beats per minute (bpm).
Time frame: Baseline through Day 127/Early Termination
Population: The safety analysis population consists of all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Clinically Significant Changes in Vital Signs | Supine SBP <90 mm Hg | 0 participants |
| Placebo | Number of Participants With Clinically Significant Changes in Vital Signs | Supine DBP <50 mm Hg | 0 participants |
| Placebo | Number of Participants With Clinically Significant Changes in Vital Signs | Increase in supine SBP >=30 mm Hg | 0 participants |
| Placebo | Number of Participants With Clinically Significant Changes in Vital Signs | Decrease in supine SBP >=30 mm Hg | 0 participants |
| Placebo | Number of Participants With Clinically Significant Changes in Vital Signs | Increase in supine DBP >=20 mm Hg | 0 participants |
| Placebo | Number of Participants With Clinically Significant Changes in Vital Signs | Decrease in supine DBP >=20 mm Hg | 0 participants |
| Placebo | Number of Participants With Clinically Significant Changes in Vital Signs | Supine pulse rate <40 bpm | 0 participants |
| Placebo | Number of Participants With Clinically Significant Changes in Vital Signs | Supine pulse rate >120 bpm | 0 participants |
| PF-06342674 0.25 mg/kg | Number of Participants With Clinically Significant Changes in Vital Signs | Supine pulse rate >120 bpm | 0 participants |
| PF-06342674 0.25 mg/kg | Number of Participants With Clinically Significant Changes in Vital Signs | Supine SBP <90 mm Hg | 0 participants |
| PF-06342674 0.25 mg/kg | Number of Participants With Clinically Significant Changes in Vital Signs | Increase in supine DBP >=20 mm Hg | 0 participants |
| PF-06342674 0.25 mg/kg | Number of Participants With Clinically Significant Changes in Vital Signs | Supine DBP <50 mm Hg | 0 participants |
| PF-06342674 0.25 mg/kg | Number of Participants With Clinically Significant Changes in Vital Signs | Supine pulse rate <40 bpm | 0 participants |
| PF-06342674 0.25 mg/kg | Number of Participants With Clinically Significant Changes in Vital Signs | Increase in supine SBP >=30 mm Hg | 0 participants |
| PF-06342674 0.25 mg/kg | Number of Participants With Clinically Significant Changes in Vital Signs | Decrease in supine DBP >=20 mm Hg | 0 participants |
| PF-06342674 0.25 mg/kg | Number of Participants With Clinically Significant Changes in Vital Signs | Decrease in supine SBP >=30 mm Hg | 0 participants |
Primary
Number of Participants With Confirmed Positive Anti-Drug Antibodies (ADAs)
Assays for the determination of a positive immune response was performed. An antibody immune response was defined as a confirmed post-treatment positive enzyme-linked immunosorbent assay (ELISA) result in combination with a negative baseline sample ELISA result. ADA positive was defined as ADA titer (ie, the reciprocal of the highest dilution that gives a value equivalent to the cut point of the assay) \>=4.32.
Time frame: Baseline, and Days 15, 29, 57, 85 and Day 127/Early Termination
Population: The safety analysis population consists of all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Confirmed Positive Anti-Drug Antibodies (ADAs) | 0 participants |
| PF-06342674 0.25 mg/kg | Number of Participants With Confirmed Positive Anti-Drug Antibodies (ADAs) | 3 participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Withdrawals Due to AEs
An AE was any untoward medical occurrence in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs are events between first dose of study drug and up to Day 127/Early Termination that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs.
Time frame: Baseline through Day 127/Early Termination
Population: The safety analysis population consists of all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Withdrawals Due to AEs | AEs | 0 participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Withdrawals Due to AEs | SAEs | 0 participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Withdrawals Due to AEs | Withdrawals Due to AEs | 0 participants |
| PF-06342674 0.25 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Withdrawals Due to AEs | AEs | 3 participants |
| PF-06342674 0.25 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Withdrawals Due to AEs | SAEs | 0 participants |
| PF-06342674 0.25 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Withdrawals Due to AEs | Withdrawals Due to AEs | 0 participants |
Primary
Number of Treatment-Emergent AEs and SAEs by Severity
AE severity was graded as mild, moderate, or severe. Mild AEs do not interfere with the participant's usual function. Moderate AEs interfere to some extent with the participant's usual function. Severe AEs interfere significantly with the participant's usual function.
Time frame: Baseline through Day 127/Early Termination
Population: The safety analysis population consists of all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Treatment-Emergent AEs and SAEs by Severity | Mild | 0 adverse events |
| Placebo | Number of Treatment-Emergent AEs and SAEs by Severity | Moderate | 0 adverse events |
| Placebo | Number of Treatment-Emergent AEs and SAEs by Severity | Severe | 0 adverse events |
| PF-06342674 0.25 mg/kg | Number of Treatment-Emergent AEs and SAEs by Severity | Mild | 7 adverse events |
| PF-06342674 0.25 mg/kg | Number of Treatment-Emergent AEs and SAEs by Severity | Moderate | 0 adverse events |
| PF-06342674 0.25 mg/kg | Number of Treatment-Emergent AEs and SAEs by Severity | Severe | 0 adverse events |
Secondary
Concentration of PF-06342674
Time frame: Baseline through Day 127/Early Termination
Population: Participants in the placebo arm did not receive PF-06342674. Due to the early termination of the study, the small enrollment number and minimal data, concentration data were listed but not summarized, and pharmacokinetic (PK) parameters were not calculated for the PF-06342674 0.25 mg/kg arm.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| PF-06342674 0.25 mg/kg | Concentration of PF-06342674 | NA nanogram/milliliter (ng/ml) |