A Study To Evaluate The Safety And Tolerability Of PF-06342674 (RN168) In Subjects With Multiple Sclerosis (MS)

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 1b, Double-blinded, Placebo-controlled, Randomized Study To Evaluate The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of Multiple Ascending Doses Of Pf-06342674 (rn168) In Subjects With Multiple Sclerosis (ms)

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Biological: PF-06342674 0.25 mg/kg
* Biological: Placebo
* Biological: PF-06342674 1.5 mg/kg
* Biological: PF-06342674 6.0 mg/kg


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br> | Biological: PF-06342674 0.25 mg/kg<br>* Bi-Weekly Subcutaneous Injections X 6<br>Biological: Placebo<br>* Bi-Weekly Subcutaneous Injections X 6<br>|
| Experimental: PF-06342674 1.5 mg/kg<br> | Biological: Placebo<br>* Bi-Weekly Subcutaneous Injections X 6<br>Biological: PF-06342674 1.5 mg/kg<br>* Bi-Weekly Subcutaneous Injections X 6<br>|
| Experimental: PF-06342674 6.0 mg/kg (q2 Weeks)<br> | Biological: Placebo<br>* Bi-Weekly Subcutaneous Injections X 6<br>Biological: PF-06342674 6.0 mg/kg<br>* Bi-Weekly Subcutaneous Injections X 6<br>|
| Experimental: PF-06342674 6.0 mg/kg (q1 Week)<br> | Biological: Placebo<br>* Bi-Weekly Subcutaneous Injections X 6<br>Biological: PF-06342674 6.0 mg/kg<br>* Bi-Weekly Subcutaneous Injections X 6<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline through Day 127/Early Termination | 
| 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. | Baseline through Day 127/Early Termination | 
| 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). | Baseline through Day 127/Early Termination | 
| 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). | Baseline through Day 127/Early Termination | 
| 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. | Baseline through Day 127/Early Termination | 
| 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. | Baseline, and Days 15, 29, 57, 85 and Day 127/Early Termination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of PF-06342674 |  | Baseline through Day 127/Early Termination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Sclerosis, MRI