Clinical trial NCT03334851: Safety and Tolerability Study Of PF-06835375 In Subjects With Seropositive Systemic Lupus Erythematosus Or Rheumatoid Arthritis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Systemic Lupus Erythematosus
Rheumatoid Arthritis
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2017-11-07
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: Inclusion Criteria:

* Patients with Rheumatoid Arthritis: confirmed diagnosis according to 2010 ACR/EULAR criteria with symptom duration at least 6 months and positive with Rheumatoid Factor and/or anti citrullinated peptide antibody
* Patients with Systemic Lupus Erythematosus: Confirmed diagnosis according to the SLICC Classification Criteria with symptom duration at least 6 months and at least one of the following: positive antinuclear antibody titer, positive anti-dsDNA, anti-Smith antibodies

Exclusion Criteria:

* Active central nervous system manifestations, systemic vasculitis or pleuro/pericarditis
* Active lupus nephritis
* Treatment with B cell depleting agents within 52 weeks prior to screening

Primary outcomes:
measure: Number of Participants With Dose-Limiting Toxicity (DLT)
timeFrame: 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)
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity
timeFrame: 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)
measure: Number of Participants With All-Causality and Treatment-Related TEAEs
timeFrame: 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)
measure: Number of Participants With Permanent Discontinuation Due to TEAEs
timeFrame: 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)
measure: Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis
timeFrame: 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)
measure: Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria
timeFrame: 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)
measure: Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria
timeFrame: 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)
measure: Number of Participants With All-Causality and Treatment-Related Infections and Infestations
timeFrame: 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:
measure: B Cell Maximum Decrease (%) From Baseline Over Time Following Single and Multiple Doses of PF-06835375
timeFrame: 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)
measure: cTfh Cell Depletion Maximum Decrease (%) From Baseline Over Time Following Single and Multiple Doses of PF-06835375
timeFrame: 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)
measure: Maximum Observed Serum Concentration (Cmax) of PF-06835375 in Part A (SAD)
timeFrame: 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
measure: Time to Reach Cmax (Tmax) of PF-06835375 in Part A (SAD)
timeFrame: 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
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-06835375 in Part A (SAD)
timeFrame: 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
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-06835375 in Part A (SAD)
timeFrame: 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
measure: Cmax of PF-06835375 Following First Dose and Multiple Doses in Part B (MAD)
timeFrame: Day 1 (pre-dose, 2, 4, 6, 8, 12 hours post dose), 2, 4, 8 and 15 for Day 1 PK estimates; Day 29 (pre-dose, 2, 4, 6, 8, hours post dose), 36, 43, 57, 85 and 113 for Day 29 PK estimates
measure: Tmax of PF-06835375 Following First Dose and Multiple Doses in Part B (MAD)
timeFrame: Day 1 (pre-dose, 2, 4, 6, 8, 12 hours post dose), 2, 4, 8 and 15 for Day 1 PK estimates; Day 29 (pre-dose, 2, 4, 6, 8, hours post dose), 36, 43, 57, 85 and 113 for Day 29 PK estimates
measure: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06835375 Following First Dose and Multiple Doses in Part B (MAD)
timeFrame: Day 1 (pre-dose, 2, 4, 6, 8, 12 hours post dose), 2, 4, 8 and 15 for Day 1 PK estimates; Day 29 (pre-dose, 2, 4, 6, 8, hours post dose), 36, 43, 57, 85 and 113 for Day 29 PK estimates
measure: AUClast of PF-06835375 Following Multiple Doses in Part B (MAD)
timeFrame: Day 29 (pre-dose, 2, 4, 6, 8, hours post dose), 36, 43, 57, 85 and 113 for Day 29 PK estimates
measure: Minimum Observed Serum Trough Concentration (Cmin) of PF-06835375 Following Multiple Doses in Part B (MAD)
timeFrame: Day 29 (pre-dose, 2, 4, 6, 8, hours post dose), 36, 43, 57, 85 and 113 for Day 29 PK estimates
measure: Observed Accumulation Ratio (Rac) of PF-06835375 Following Multiple Doses in Part B (MAD)
timeFrame: Day 1 (pre-dose, 2, 4, 6, 8, 12 hours post dose), 2, 4, 8 and 15 for Day 1 PK estimates; Day 29 (pre-dose, 2, 4, 6, 8, hours post dose), 36, 43, 57, 85 and 113 for Day 29 PK estimates
measure: Peak-to-trough Fluctuation (PTF) of PF-06835375 Following Multiple Doses in Part B (MAD)
timeFrame: Day 29 (pre-dose, 2, 4, 6, 8, hours post dose), 36, 43, 57, 85 and 113 for Day 29 PK estimates
measure: Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06835375
timeFrame: Day 1, 15, 29, 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)
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Pinnacle Research Group, LLC
state: Alabama
city: Anniston
country: United States
facility: Pinnacle Research Group, LLC
state: Alabama
city: Beverly Hills
country: United States
facility: Wallace Rheumatic Studies Center
state: California
city: Los Angeles
country: United States
facility: Prive aftercare
state: California
city: Clearwater
country: United States
facility: Clinical Research of West Florida, Inc.
state: Florida
city: Clearwater
country: United States
facility: Private Practice of Robert W. Levin, MD
state: Florida
city: DeLand
country: United States
facility: Avail Clinical Research
state: Florida
city: Orlando
country: United States
facility: Omega Research Maitland, LLC
state: Florida
city: South Miami
country: United States
facility: Larkin Hospital
state: Florida
city: South Miami
country: United States
facility: Qps Mra, Llc
state: Florida
city: South Miami
country: United States
facility: Qps-Mra, Llc
state: Florida
city: Baltimore
country: United States
facility: PAREXEL International - EPCU Baltimore
state: Maryland
city: Catonsville
country: United States
facility: Rheumatology Express
state: Maryland
city: Raleigh
country: United States
facility: Carolina Phase 1 Research, LLC
state: North Carolina
city: Duncansville
country: United States
facility: Altoona Center for Clinical Research
state: Pennsylvania
city: Dallas
country: United States
facility: Metroplex Clinical Research Center
state: Texas
city: Dallas
country: United States
facility: MPP Infusion Centers
state: Texas
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: