NCT03334851|CompletedPhase 1ResultsFDA Drug

Safety and Tolerability Study Of PF-06835375 In Subjects With Seropositive Systemic Lupus Erythematosus Or Rheumatoid Arthritis

A PHASE 1, RANDOMIZED, MULTI-CENTER, DOUBLE-BLIND, SPONSOR OPEN, PLACEBO-CONTROLLED, SINGLE AND MULTIPLE DOSE-ESCALATION STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS AND PHARMACODYNAMICS OF PF-06835375 IN SUBJECTS WITH SEROPOSITIVE SYSTEMIC LUPUS ERYTHEMATOSUS OR RHEUMATOID ARTHRITIS

Pfizer ClinicalTrials.gov

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2 other identifiers

C11310012017-003077-34

Study Type

interventional

Target

Locations

1 country

Sites

Timeline

RegisteredNov 2017

StartedNov 2017

CompletionFeb 2022

Brief Summary

This is a Phase 1 single and multiple dose escalation study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of PF-06835375 in subjects with seropositive SLE or RA. The design is double-blind, sponsor open and placebo controlled. This study will include two parts: Part A and Part B. Part A will consist of single ascending dose cohorts, Part B of multiple ascending dose cohorts. This study will enroll up to a total of approximately 112 subjects at approximately 10 sites.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at P75+ for phase_1

Timeline

Completed

Started Nov 2017

Longer than P75 for phase_1

Geographic Reach

1 country

17 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

4.2 years study duration

First Submitted

Initial submission to the registry

November 3, 2017

Completed

4 days until next milestone

First Posted

Study publicly available on registry

November 7, 2017

Completed

10 days until next milestone

Study Start

First participant enrolled

November 17, 2017

Completed

4.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 15, 2022

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 15, 2022

Completed

1.7 years until next milestone

Results Posted

Study results publicly available

October 30, 2023

Completed

Last Updated

October 30, 2023

Status Verified

January 1, 2023

Enrollment Period

4.2 years

First QC Date

November 3, 2017

Results QC Date

January 10, 2023

Last Update Submit

January 10, 2023

Conditions

Systemic Lupus Erythematosus Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (8)

Number of Participants With Dose-Limiting Toxicity (DLT)
DLT was defined as any of the following events meeting the criteria: (1) \>=2 participants within a dose cohort developed Common Terminology Criteria for Adverse Events (CTCAE) v4.0 Grade 3 adverse event considered to be serious in the same organ system or 1 participant developed a CTCAE v4.0 Grade 4 or higher SAE considered related to study drug; (2) 50% or more participants within a dose cohort experienced a CTCAE v4.0 Grade 3 or higher infusion reaction; (3) a confirmed or probable case of Progressive Multifocal Leukoencephalopathy was observed; (4) the mean exposure for the treatment group reached or exceeded the exposure stopping limit of Cav of 261 mg/mL, or, based on the observed data, the group mean Cav of the next planned dose was projected to exceed the exposure stopping limit. Cav = average serum concentration.
From the first dose of study treatment up to 7-14 days after end of study criteria met (maximum duration for end of study criteria met: Day 225 for Part A, Day 281 for Part B)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Relatedness to study drug was assessed by the investigator. Treatment-emergent were events between first dose of study drug and up to approximately Week 40 that were absent before treatment or that worsened relative to pretreatment state. AEs are classified according to the severity in 3 categories a) mild - AEs does not interfere with participant's usual function b) moderate - AEs interferes to some extent with participant's usual function c) severe - AEs interferes significantly with participant's usual function.
From the first dose of study treatment up to 7-14 days after end of study criteria met (maximum duration for end of study criteria met: Day 225 for Part A, Day 281 for Part B)
Number of Participants With All-Causality and Treatment-Related TEAEs
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Relatedness to study drug was assessed by the investigator. A serious adverse event (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 were events between first dose of study drug and up to approximately Week 40 that were absent before treatment or that worsened relative to pretreatment state.
From the first dose of study treatment up to 7-14 days after end of study criteria met (maximum duration for end of study criteria met: Day 225 for Part A, Day 281 for Part B)
Number of Participants With Permanent Discontinuation Due to TEAEs
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent were events between first dose of study drug and up to approximately Week 40 that were absent before treatment or that worsened relative to pretreatment state.
From the first dose of study treatment up to 7-14 days after end of study criteria met (maximum duration for end of study criteria met: Day 225 for Part A, Day 281 for Part B)
Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis
Hematology included hemoglobin, hematocrit, red blood cell, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet and white blood cell count, total neutrophils, eosinophils, monocytes, basophils and lymphocytes. Chemistry included blood urea nitrogen, creatinine, glucose, calcium, sodium, potassium, chloride, bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid, albumin, total protein and creatine kinase. Urinalysis included pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, urobilinogen, urine bilirubin, microscopy and creatinine. Clinical significance was judged by the investigator and those met the criteria of AE are listed here. Clinically significant laboratory abnormalities reported for at least 1 participant in the whole study are presented here. Baseline was the last pre-dose measurement (first treatment for MAD cohorts).
From baseline up to end of study criteria met (maximum duration for end of study criteria met: Day 225 for Part A, Day 281 for Part B)
Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria
Criteria for abnormality in vital signs: supine pulse rate \<40 beats per minute (bpm) or \>120 bpm; standing pulse rate \<40 bpm or \>120 bpm; sitting systolic blood pressure (BP) \<90 mmHg, maximum increase or decrease from baseline of \>=30 mmHg; sitting diastolic BP \<50 mmHg, maximum increase or decrease from baseline of \>=20 mmHg. Baseline was defined as the last pre-dose measurement in Day 1. Only those categories in which at least 1 participant had data were reported.
From baseline up to end of study criteria met (maximum duration for end of study criteria met: Day 225 for Part A, Day 281 for Part B)
Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria
ECG abnormalities criteria included: 1) maximum QTc interval (ms): 450\<= QTc \<480, 480\<= QTc \<500, and QTc \>=500; QTc maximum increase from baseline (ms): 30\<= change \<60, and change \>=60; 2) maximum PR interval (ms): \>=300; PR increase from baseline (ms): baseline \>200 with 25% increase at maximum, baseline \<=200 with 50% increase at maximum; 3) maximum QRS (ms): \>=140; QRS increase from baseline (ms) \>=50%. QTcF indicates QT interval corrected using the Fridericia's formula. QTcB indicates QT interval corrected using the Bazett's formula. Baseline was defined as the average of the triplicate pre-dose recordings at Day 1. Only those categories in which at least 1 participant had data were reported.
From baseline up to end of study criteria met (maximum duration for end of study criteria met: Day 225 for Part A, Day 281 for Part B)
Number of Participants With All-Causality and Treatment-Related Infections and Infestations
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Relatedness to study drug was assessed by the investigator. The incidence of AEs by system organ class "infections and infestations" was reported here.
From the first dose of study treatment up to 7-14 days after end of study criteria met (maximum duration for end of study criteria met: Day 225 for Part A, Day 281 for Part B)

Secondary Outcomes (14)

B Cell Maximum Decrease (%) From Baseline Over Time Following Single and Multiple Doses of PF-06835375
Screening, Day 1, 2, 4, 8, 15, 29, 36 (Part B only), 43, 57, 85, 113, and every 4 weeks until criteria for end of study met (maximum duration for end of study criteria met: Day 225 for Part A, Day 281 for Part B)
cTfh Cell Depletion Maximum Decrease (%) From Baseline Over Time Following Single and Multiple Doses of PF-06835375
Screening, Day 1, 2, 4, 8, 15, 29, 36 (Part B only), 43, 57, 85, 113, and every 4 weeks until criteria for end of study met (maximum duration for end of study criteria met: Day 225 for Part A, Day 281 for Part B)
Maximum Observed Serum Concentration (Cmax) of PF-06835375 in Part A (SAD)
Day 1 (pre-dose, 2, 4, 6, 8, 12 hours post dose), 2, 4, 8, 15, 29, 43, 57, 85, 113 and 141 for Day 1 PK estimates
Time to Reach Cmax (Tmax) of PF-06835375 in Part A (SAD)
Day 1 (pre-dose, 2, 4, 6, 8, 12 hours post dose), 2, 4, 8, 15, 29, 43, 57, 85, 113 and 141 for Day 1 PK estimates
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-06835375 in Part A (SAD)
Day 1 (pre-dose, 2, 4, 6, 8, 12 hours post dose), 2, 4, 8, 15, 29, 43, 57, 85, 113 and 141 for Day 1 PK estimates
+9 more secondary outcomes

Study Arms (14)

Part A, Cohort 1

EXPERIMENTAL

Subjects will receive a single dose of PF-06835375 or placebo on Day 1 via intravenous administration