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

• ClinicalTrials.gov Identifier: NCT03334851
• Recruitment Status: Completed
• First Posted: November 7, 2017
• Last Update Posted: April 7, 2022
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Systemic Lupus Erythematosus; Rheumatoid Arthritis	Drug: PF-06835375; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 74 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Basic Science
• 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
• Actual Study Start Date: November 17, 2017
• Actual Primary Completion Date: February 15, 2022
• Actual Study Completion Date: February 15, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Part A, Cohort 1; Subjects will receive a single dose of PF-06835375 or placebo on Day 1 via intravenous administration	Drug: PF-06835375; Intravenous (IV) or subcutaneous (SC) administration. Subjects will receive one or two doses. Doses will be ascending and determined by emerging data.; Drug: Placebo; Matching placebo for PF-06835375 IV or SC. Subjects will receive one or two doses.
Experimental: Part A, Cohort 2; Subjects will receive a single dose of PF-06835375 or placebo on Day 1 via intravenous administration.	Drug: PF-06835375; Intravenous (IV) or subcutaneous (SC) administration. Subjects will receive one or two doses. Doses will be ascending and determined by emerging data.; Drug: Placebo; Matching placebo for PF-06835375 IV or SC. Subjects will receive one or two doses.
Experimental: Part A, Cohort 3; Subjects will receive a single dose of PF-06835375 or placebo on Day 1 via intravenous administration.	Drug: PF-06835375; Intravenous (IV) or subcutaneous (SC) administration. Subjects will receive one or two doses. Doses will be ascending and determined by emerging data.; Drug: Placebo; Matching placebo for PF-06835375 IV or SC. Subjects will receive one or two doses.
Experimental: Part A, Cohort 4; Subjects will receive a single dose of PF-06835375 or placebo on Day 1 via intravenous administration.	Drug: PF-06835375; Intravenous (IV) or subcutaneous (SC) administration. Subjects will receive one or two doses. Doses will be ascending and determined by emerging data.; Drug: Placebo; Matching placebo for PF-06835375 IV or SC. Subjects will receive one or two doses.
Experimental: Part A, Cohort 5; Subjects will receive a single dose of PF-06835375 or placebo on Day 1 via intravenous administration.	Drug: PF-06835375; Intravenous (IV) or subcutaneous (SC) administration. Subjects will receive one or two doses. Doses will be ascending and determined by emerging data.; Drug: Placebo; Matching placebo for PF-06835375 IV or SC. Subjects will receive one or two doses.
Experimental: Part A, Cohort 6; Subjects will receive a single dose of PF-06835375 or placebo on Day 1 via intravenous administration.	Drug: PF-06835375; Intravenous (IV) or subcutaneous (SC) administration. Subjects will receive one or two doses. Doses will be ascending and determined by emerging data.; Drug: Placebo; Matching placebo for PF-06835375 IV or SC. Subjects will receive one or two doses.
Experimental: Part A, Cohort 7; Subjects will receive a single dose of PF-06835375 or placebo on Day 1 via intravenous administration.	Drug: PF-06835375; Intravenous (IV) or subcutaneous (SC) administration. Subjects will receive one or two doses. Doses will be ascending and determined by emerging data.; Drug: Placebo; Matching placebo for PF-06835375 IV or SC. Subjects will receive one or two doses.
Experimental: Part A, Cohort 8; Subjects will receive a single dose of PF-06835375 or placebo on Day 1 via intravenous administration.	Drug: PF-06835375; Intravenous (IV) or subcutaneous (SC) administration. Subjects will receive one or two doses. Doses will be ascending and determined by emerging data.; Drug: Placebo; Matching placebo for PF-06835375 IV or SC. Subjects will receive one or two doses.
Experimental: Part B, Cohort 1; Subjects will receive two doses of PF-06835375 or placebo on Day 1 and Day 29 via subcutaneous administration.	Drug: PF-06835375; Intravenous (IV) or subcutaneous (SC) administration. Subjects will receive one or two doses. Doses will be ascending and determined by emerging data.; Drug: Placebo; Matching placebo for PF-06835375 IV or SC. Subjects will receive one or two doses.
Experimental: Part B, Cohort 2; Subjects will receive two doses of PF-06835375 or placebo on Day 1 and Day 29 via subcutaneous or intravenous administration.	Drug: PF-06835375; Intravenous (IV) or subcutaneous (SC) administration. Subjects will receive one or two doses. Doses will be ascending and determined by emerging data.; Drug: Placebo; Matching placebo for PF-06835375 IV or SC. Subjects will receive one or two doses.
Experimental: Part B, Cohort 3; Subjects will receive two doses of PF-06835375 or placebo on Day 1 and Day 29 via subcutaneous or intravenous administration.	Drug: PF-06835375; Intravenous (IV) or subcutaneous (SC) administration. Subjects will receive one or two doses. Doses will be ascending and determined by emerging data.; Drug: Placebo; Matching placebo for PF-06835375 IV or SC. Subjects will receive one or two doses.
Experimental: Part B, Cohort 4; Subjects will receive two doses of PF-06835375 or placebo on Day 1 and Day 29 via subcutaneous or intravenous administration.	Drug: PF-06835375; Intravenous (IV) or subcutaneous (SC) administration. Subjects will receive one or two doses. Doses will be ascending and determined by emerging data.; Drug: Placebo; Matching placebo for PF-06835375 IV or SC. Subjects will receive one or two doses.
Experimental: Part B, Cohort 5; Subjects will receive two doses of PF-06835375 or placebo on Day 1 and Day 29 via subcutaneous or intravenous administration.	Drug: PF-06835375; Intravenous (IV) or subcutaneous (SC) administration. Subjects will receive one or two doses. Doses will be ascending and determined by emerging data.; Drug: Placebo; Matching placebo for PF-06835375 IV or SC. Subjects will receive one or two doses.
Experimental: Part B, cohort 6; Subjects will receive two doses of PF-06835375 or placebo on Day 1 and Day 29 via subcutaneous or intravenous administration.	Drug: PF-06835375; Intravenous (IV) or subcutaneous (SC) administration. Subjects will receive one or two doses. Doses will be ascending and determined by emerging data.; Drug: Placebo; Matching placebo for PF-06835375 IV or SC. Subjects will receive one or two doses.

Outcome Measures

Primary Outcome Measures :

1. Number of participants with adverse events (AEs) by seriousness and relationship to treatment [ Time Frame: Day 1 through approximately Day 112 ]
2. Number of participants with change from baseline in labboratory test results [ Time Frame: Day 1 through approximately Day 112 ]
3. Number of participants with clinically relevant changes from baseline in ECG parameters [ Time Frame: Day 1 through approximately Day 112 ]
4. Number of participants with infections [ Time Frame: Day 1 through approximately Day 112 ]
5. Number of participants with clinically relevant changes from baseline in vital signs [ Time Frame: Day 1 through approximately Day 112 ]
6. Number of participants with dose limiting adverse events [ Time Frame: Day 1 through approximately Day 112 ]

Secondary Outcome Measures :

1. Change from baseline in the number of specific B cells (subset) over time following single and multiple doses of PF-06835375 [ Time Frame: Day 1 through approximately Day 112 ]
2. Change from baseline in the number of specific T cells (subset) over time following single and multiple doses of PF-06835375 [ Time Frame: Day 1 through approximately Day 112 ]
3. Number of participants with anti-drug antibodies (ADA) to PF-06835375 [ Time Frame: Day 1 through approximately Day 112 ]
4. Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of PF-06835375 [ Time Frame: Day 1 through approximately Day 112 ]
5. Maximum Observed Plasma Concentration (Cmax) of PF-06835375 [ Time Frame: Day 1 through approximately Day 112 ]
6. Number of participants with neutralizing antibodies to PF-06835375 [ Time Frame: Day 1 through approximately Day 112 ]
7. Apparent Clearance (CL) of PF-06835375 [ Time Frame: Day 1 through approximately Day 112 ]
8. Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of PF-06835375 [ Time Frame: Day 1 through approximately Day 112 ]
9. Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06835375 [ Time Frame: Day 1 through approximately Day 112 ]
10. Plasma Decay Half-Life of PF-06835375 [ Time Frame: Day 1 to approximately Day 112 ]
11. Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06835375 [ Time Frame: Day 1 through approximately Day 112 ]
12. Volume of Distribution at Steady State (Vss) of PF-06835375 [ Time Frame: Day 1 through approximately Day 112 ]
13. AUCtau of PF-06835375 (dose normalized) [ Time Frame: Day 1 through approximately Day 112 ]
14. Average Concentration (Cav) of PF-06835375 [ Time Frame: Day 1 through approximately Day 112 ]
15. Mean residence of time for PF-06835375 [ Time Frame: Day 1 though approximately Day 112 ]
16. Maximum Observed Plasma Concentration (Cmax) dose normalized of PF-06835375 [ Time Frame: Day 1 through approximately Day 112 ]
17. Bioavailability of PF-06835375 subcutaneous doses compared to intravenous doses of PF-06835375 [ Time Frame: Day 1 through approximately Day 112 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Alabama

Pinnacle Research Group, LLC

Anniston, Alabama, United States, 36201

Pinnacle Research Group, LLC

Anniston, Alabama, United States, 36207

United States, California

Wallace Rheumatic Studies Center

Beverly Hills, California, United States, 90211

Prive aftercare

Los Angeles, California, United States, 90048

United States, Florida

Clinical Research of West Florida, Inc.

Clearwater, Florida, United States, 33765

Private Practice of Robert W. Levin, MD

Clearwater, Florida, United States, 33765

Avail Clinical Research

DeLand, Florida, United States, 32720

Omega Research Maitland, LLC

Orlando, Florida, United States, 32808

Omega Research Maitland

Orlando, Florida, United States, 32810

Larkin Hospital

South Miami, Florida, United States, 33143

Qps Mra, Llc

South Miami, Florida, United States, 33143

Qps-Mra, Llc

South Miami, Florida, United States, 33143

United States, Maryland

PAREXEL International - EPCU Baltimore

Baltimore, Maryland, United States, 21225

Rheumatology Express

Catonsville, Maryland, United States, 21228

United States, North Carolina

Carolina Phase 1 Research, LLC

Raleigh, North Carolina, United States, 27612

United States, Pennsylvania

Altoona Center for Clinical Research

Duncansville, Pennsylvania, United States, 16635

United States, Texas

Metroplex Clinical Research Center

Dallas, Texas, United States, 75231

MPP Infusion Centers

Dallas, Texas, United States, 75231

Sponsors and Collaborators

Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

More Information

Additional Information:

To obtain contact information for a study center near you, click here. 

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT03334851
• Other Study ID Numbers: C1131001; 2017-003077-34 ( EudraCT Number )
• First Posted: November 7, 2017
• Last Update Posted: April 7, 2022
• Last Verified: April 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Arthritis; Arthritis, Rheumatoid; Lupus Erythematosus, Systemic; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases