Safety and Tolerability Study Of PF-06835375 In Subjects With Seropositive Systemic Lupus Erythematosus Or Rheumatoid Arthritis
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
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
- Number of participants with adverse events (AEs) by seriousness and relationship to treatment [Day 1 through approximately Day 112]
- Number of participants with change from baseline in labboratory test results [Day 1 through approximately Day 112]
- Number of participants with clinically relevant changes from baseline in ECG parameters [Day 1 through approximately Day 112]
- Number of participants with infections [Day 1 through approximately Day 112]
- Number of participants with clinically relevant changes from baseline in vital signs [Day 1 through approximately Day 112]
- Number of participants with dose limiting adverse events [Day 1 through approximately Day 112]
Secondary Outcome Measures
- 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]
- 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]
- Number of participants with anti-drug antibodies (ADA) to PF-06835375 [Day 1 through approximately Day 112]
- Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of PF-06835375 [Day 1 through approximately Day 112]
- Maximum Observed Plasma Concentration (Cmax) of PF-06835375 [Day 1 through approximately Day 112]
- Number of participants with neutralizing antibodies to PF-06835375 [Day 1 through approximately Day 112]
- Apparent Clearance (CL) of PF-06835375 [Day 1 through approximately Day 112]
- Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of PF-06835375 [Day 1 through approximately Day 112]
- Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06835375 [Day 1 through approximately Day 112]
- Plasma Decay Half-Life of PF-06835375 [Day 1 to approximately Day 112]
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06835375 [Day 1 through approximately Day 112]
- Volume of Distribution at Steady State (Vss) of PF-06835375 [Day 1 through approximately Day 112]
- AUCtau of PF-06835375 (dose normalized) [Day 1 through approximately Day 112]
- Average Concentration (Cav) of PF-06835375 [Day 1 through approximately Day 112]
- Mean residence of time for PF-06835375 [Day 1 though approximately Day 112]
- Maximum Observed Plasma Concentration (Cmax) dose normalized of PF-06835375 [Day 1 through approximately Day 112]
- Bioavailability of PF-06835375 subcutaneous doses compared to intravenous doses of PF-06835375 [Day 1 through approximately Day 112]
Eligibility Criteria
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
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.- C1131001
- 2017-003077-34