Trial Outcomes & Findings for A Study To Evaluate The Safety And Tolerability Of PF-06342674 (RN168) In Subjects With Multiple Sclerosis (MS) (NCT NCT02045732)

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

4 participants

Primary outcome timeframe

Baseline through Day 127/Early Termination

Results posted on

2017-01-16

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Placebo Participants received placebo subcutaneously (SC) every other week during an 85-day treatment period.	PF-06342674 0.25 mg/kg Participants received PF-06342674 0.25 milligram (mg)/kilogram (kg) SC every other week during an 85-day treatment period.
Overall Study STARTED	1	3
Overall Study COMPLETED	0	2
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received placebo subcutaneously (SC) every other week during an 85-day treatment period.	PF-06342674 0.25 mg/kg Participants received PF-06342674 0.25 milligram (mg)/kilogram (kg) SC every other week during an 85-day treatment period.
Overall Study At the discretion of the investigator	1	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=1 Participants Participants received placebo SC every other week during an 85-day treatment period.	PF-06342674 0.25 mg/kg n=3 Participants Participants received PF-06342674 0.25 mg/kg SC every other week during an 85-day treatment period.	Total n=4 Participants Total of all reporting groups
Age, Continuous	33 years STANDARD_DEVIATION 0 • n=5 Participants	45.3 years STANDARD_DEVIATION 14.2 • n=7 Participants	42.3 years STANDARD_DEVIATION 13.1 • n=5 Participants
Gender Female	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Gender Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline through Day 127/Early Termination

Population: The safety analysis population consists of all participants who received at least 1 dose of study drug.

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.

Outcome measures

Outcome measures
Measure	Placebo n=1 Participants Participants received placebo SC every other week during an 85-day treatment period.	PF-06342674 0.25 mg/kg n=3 Participants Participants received PF-06342674 0.25 mg/kg SC every other week during an 85-day treatment period.
Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Withdrawals Due to AEs AEs	0 participants	3 participants
Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Withdrawals Due to AEs SAEs	0 participants	0 participants
Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Withdrawals Due to AEs Withdrawals Due to AEs	0 participants	0 participants

PRIMARY outcome

Timeframe: Baseline through Day 127/Early Termination

Population: The safety analysis population consists of all participants who received at least 1 dose of study drug.

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.

Outcome measures

Outcome measures
Measure	Placebo n=1 Participants Participants received placebo SC every other week during an 85-day treatment period.	PF-06342674 0.25 mg/kg n=3 Participants Participants received PF-06342674 0.25 mg/kg SC every other week during an 85-day treatment period.
Number of Treatment-Emergent AEs and SAEs by Severity Mild	0 adverse events	7 adverse events
Number of Treatment-Emergent AEs and SAEs by Severity Moderate	0 adverse events	0 adverse events
Number of Treatment-Emergent AEs and SAEs by Severity Severe	0 adverse events	0 adverse events

PRIMARY outcome

Timeframe: Baseline through Day 127/Early Termination

Population: The safety analysis population consists of all participants who received at least 1 dose of study drug.

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).

Outcome measures

Outcome measures
Measure	Placebo n=1 Participants Participants received placebo SC every other week during an 85-day treatment period.	PF-06342674 0.25 mg/kg n=3 Participants Participants received PF-06342674 0.25 mg/kg SC every other week during an 85-day treatment period.
Number of Participants With Clinical Laboratory Abnormalities	0 participants	3 participants

PRIMARY outcome

Timeframe: Baseline through Day 127/Early Termination

Population: The safety analysis population consists of all participants who received at least 1 dose of study drug.

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).

Outcome measures

Outcome measures
Measure	Placebo n=1 Participants Participants received placebo SC every other week during an 85-day treatment period.	PF-06342674 0.25 mg/kg n=3 Participants Participants received PF-06342674 0.25 mg/kg SC every other week during an 85-day treatment period.
Number of Participants With Clinically Significant Changes in Vital Signs Supine SBP <90 mm Hg	0 participants	0 participants
Number of Participants With Clinically Significant Changes in Vital Signs Supine DBP <50 mm Hg	0 participants	0 participants
Number of Participants With Clinically Significant Changes in Vital Signs Increase in supine SBP >=30 mm Hg	0 participants	0 participants
Number of Participants With Clinically Significant Changes in Vital Signs Decrease in supine SBP >=30 mm Hg	0 participants	0 participants
Number of Participants With Clinically Significant Changes in Vital Signs Increase in supine DBP >=20 mm Hg	0 participants	0 participants
Number of Participants With Clinically Significant Changes in Vital Signs Decrease in supine DBP >=20 mm Hg	0 participants	0 participants
Number of Participants With Clinically Significant Changes in Vital Signs Supine pulse rate <40 bpm	0 participants	0 participants
Number of Participants With Clinically Significant Changes in Vital Signs Supine pulse rate >120 bpm	0 participants	0 participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=1 Participants Participants received placebo SC every other week during an 85-day treatment period.	PF-06342674 0.25 mg/kg n=3 Participants Participants received PF-06342674 0.25 mg/kg SC every other week during an 85-day treatment period.
Number of Participants With Abnormal Electrocardiogram (ECG) QTcF Interval 450-<480 msec	1 participants	0 participants
Number of Participants With Abnormal Electrocardiogram (ECG) QTcF Interval >=480 msec	0 participants	0 participants
Number of Participants With Abnormal Electrocardiogram (ECG) QTcF Interval 30-<60 msec Increase From Baseline	0 participants	0 participants
Number of Participants With Abnormal Electrocardiogram (ECG) QTcF Interval >=60 msec Increase From Baseline	0 participants	0 participants
Number of Participants With Abnormal Electrocardiogram (ECG) QTcF Interval 30-<60 msec Decrease From Baseline	1 participants	0 participants
Number of Participants With Abnormal Electrocardiogram (ECG) QTcF Interval >=60 msec Decrease From Baseline	0 participants	0 participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=1 Participants Participants received placebo SC every other week during an 85-day treatment period.	PF-06342674 0.25 mg/kg n=3 Participants Participants received PF-06342674 0.25 mg/kg SC every other week during an 85-day treatment period.
Number of Participants With Confirmed Positive Anti-Drug Antibodies (ADAs)	0 participants	3 participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo Participants received placebo SC every other week during an 85-day treatment period.	PF-06342674 0.25 mg/kg n=3 Participants Participants received PF-06342674 0.25 mg/kg SC every other week during an 85-day treatment period.
Concentration of PF-06342674	—	NA nanogram/milliliter (ng/ml) Geometric Coefficient of Variation NA Due to the early termination of the study, the small enrollment number and minimal data, concentration data were not summarized.

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

PF-06342674

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Placebo n=1 participants at risk Participants received placebo SC every other week during an 85-day treatment period.	PF-06342674 n=3 participants at risk Participants received PF-06342674 0.25 mg/kg SC every other week during an 85-day treatment period.
Gastrointestinal disorders Diarrhoea	0.00% 0/1 • Baseline through Day 127/Early Termination.	33.3% 1/3 • Baseline through Day 127/Early Termination.
Gastrointestinal disorders Nausea	0.00% 0/1 • Baseline through Day 127/Early Termination.	33.3% 1/3 • Baseline through Day 127/Early Termination.
General disorders Fatigue	0.00% 0/1 • Baseline through Day 127/Early Termination.	33.3% 1/3 • Baseline through Day 127/Early Termination.
Infections and infestations Upper respiratory tract infection	0.00% 0/1 • Baseline through Day 127/Early Termination.	66.7% 2/3 • Baseline through Day 127/Early Termination.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/1 • Baseline through Day 127/Early Termination.	33.3% 1/3 • Baseline through Day 127/Early Termination.
Nervous system disorders Headache	0.00% 0/1 • Baseline through Day 127/Early Termination.	33.3% 1/3 • Baseline through Day 127/Early Termination.

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER