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

Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT03334851
Collaborator
(none)
74
18
14
51
4.1
0.1

Study Details

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
Phase 1

Study Design

Study Type:
Interventional
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 :
Nov 17, 2017
Actual Primary Completion Date :
Feb 15, 2022
Actual Study Completion Date :
Feb 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 [Day 1 through approximately Day 112]

  2. Number of participants with change from baseline in labboratory test results [Day 1 through approximately Day 112]

  3. Number of participants with clinically relevant changes from baseline in ECG parameters [Day 1 through approximately Day 112]

  4. Number of participants with infections [Day 1 through approximately Day 112]

  5. Number of participants with clinically relevant changes from baseline in vital signs [Day 1 through approximately Day 112]

  6. Number of participants with dose limiting adverse events [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 [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 [Day 1 through approximately Day 112]

  3. Number of participants with anti-drug antibodies (ADA) to PF-06835375 [Day 1 through approximately Day 112]

  4. Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of PF-06835375 [Day 1 through approximately Day 112]

  5. Maximum Observed Plasma Concentration (Cmax) of PF-06835375 [Day 1 through approximately Day 112]

  6. Number of participants with neutralizing antibodies to PF-06835375 [Day 1 through approximately Day 112]

  7. Apparent Clearance (CL) of PF-06835375 [Day 1 through approximately Day 112]

  8. Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of PF-06835375 [Day 1 through approximately Day 112]

  9. Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06835375 [Day 1 through approximately Day 112]

  10. Plasma Decay Half-Life of PF-06835375 [Day 1 to approximately Day 112]

  11. Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06835375 [Day 1 through approximately Day 112]

  12. Volume of Distribution at Steady State (Vss) of PF-06835375 [Day 1 through approximately Day 112]

  13. AUCtau of PF-06835375 (dose normalized) [Day 1 through approximately Day 112]

  14. Average Concentration (Cav) of PF-06835375 [Day 1 through approximately Day 112]

  15. Mean residence of time for PF-06835375 [Day 1 though approximately Day 112]

  16. Maximum Observed Plasma Concentration (Cmax) dose normalized of PF-06835375 [Day 1 through approximately Day 112]

  17. Bioavailability of PF-06835375 subcutaneous doses compared to intravenous doses of PF-06835375 [Day 1 through approximately Day 112]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 70 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Site City State Country Postal Code
1 Pinnacle Research Group, LLC Anniston Alabama United States 36201
2 Pinnacle Research Group, LLC Anniston Alabama United States 36207
3 Wallace Rheumatic Studies Center Beverly Hills California United States 90211
4 Prive aftercare Los Angeles California United States 90048
5 Clinical Research of West Florida, Inc. Clearwater Florida United States 33765
6 Private Practice of Robert W. Levin, MD Clearwater Florida United States 33765
7 Avail Clinical Research DeLand Florida United States 32720
8 Omega Research Maitland, LLC Orlando Florida United States 32808
9 Omega Research Maitland Orlando Florida United States 32810
10 Larkin Hospital South Miami Florida United States 33143
11 Qps Mra, Llc South Miami Florida United States 33143
12 Qps-Mra, Llc South Miami Florida United States 33143
13 PAREXEL International - EPCU Baltimore Baltimore Maryland United States 21225
14 Rheumatology Express Catonsville Maryland United States 21228
15 Carolina Phase 1 Research, LLC Raleigh North Carolina United States 27612
16 Altoona Center for Clinical Research Duncansville Pennsylvania United States 16635
17 Metroplex Clinical Research Center Dallas Texas United States 75231
18 MPP Infusion Centers Dallas Texas United States 75231

Sponsors and Collaborators

  • Pfizer

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT03334851
Other Study ID Numbers:
  • C1131001
  • 2017-003077-34
First Posted:
Nov 7, 2017
Last Update Posted:
Apr 7, 2022
Last Verified:
Apr 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Apr 7, 2022