Phase 1
N=73
Safety and Tolerability Study Of PF-06835375 In Subjects With Seropositive Systemic Lupus Erythematosus Or Rheumatoid Arthritis
Systemic Lupus Erythematosus · Rheumatoid Arthritis
Bottom Line
View on ClinicalTrials.gov: NCT03334851 ↗Enrolled (actual)
73
Serious AEs
4.1%
Results posted
Oct 2023
Primary outcome: Primary: Number of Participants With Dose-Limiting Toxicity (DLT) — 0; 0; 0; 0 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- PF-06835375 (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Pfizer
- Primary completion
- Feb 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Dose-Limiting Toxicity (DLT) |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity |
3; 0; 1; 0; 0; 3 | — |
| PRIMARY Number of Participants With All-Causality and Treatment-Related TEAEs |
8; 3; 3; 2; 3; 6 | — |
| PRIMARY Number of Participants With Permanent Discontinuation Due to TEAEs |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis |
1; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria |
2; 0; 0; 0; 1; 1 | — |
| PRIMARY Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria |
1; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With All-Causality and Treatment-Related Infections and Infestations |
4; 2; 3; 0; 2; 1 | — |
| SECONDARY B Cell Maximum Decrease (%) From Baseline Over Time Following Single and Multiple Doses of PF-06835375 |
37.693; 67.283; 84.978; 94.052; 98.546; 98.588 | — |
| SECONDARY cTfh Cell Depletion Maximum Decrease (%) From Baseline Over Time Following Single and Multiple Doses of PF-06835375 |
45.227; 62.360; 84.994; 89.324; 98.675; 97.283 | — |
| SECONDARY Maximum Observed Serum Concentration (Cmax) of PF-06835375 in Part A (SAD) |
NA; NA; 103.0; 208.7; 994.7; 2645 | — |
| SECONDARY Time to Reach Cmax (Tmax) of PF-06835375 in Part A (SAD) |
NA; NA; 2.17; 2.08; 2.24; 3.96 | — |
| SECONDARY Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-06835375 in Part A (SAD) |
NA; 1573; 7467; 88190; 288000 | — |
| SECONDARY Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-06835375 in Part A (SAD) |
NA; NA; 1380; 7327; 87120; 287400 | — |
| SECONDARY Cmax of PF-06835375 Following First Dose and Multiple Doses in Part B (MAD) |
5.743; 34.82; 77.72; 257.8; 26.92; 89.68 | — |
| SECONDARY Tmax of PF-06835375 Following First Dose and Multiple Doses in Part B (MAD) |
170; 168; 169; 144; 169; 169 | — |
| SECONDARY 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) |
1964; 11010; 28070; 70630; 9309; 25610 | — |
| SECONDARY AUClast of PF-06835375 Following Multiple Doses in Part B (MAD) |
9346; 22050; 84370; 96610 | — |
| SECONDARY Minimum Observed Serum Trough Concentration (Cmin) of PF-06835375 Following Multiple Doses in Part B (MAD) |
NA; 6.075; 11.81; 9.410 | — |
| SECONDARY Observed Accumulation Ratio (Rac) of PF-06835375 Following Multiple Doses in Part B (MAD) |
NA; 2.410; 2.977; 2.001 | — |
| SECONDARY Peak-to-trough Fluctuation (PTF) of PF-06835375 Following Multiple Doses in Part B (MAD) |
NA; 2.037; 1.687; 1.830 | — |
| SECONDARY Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06835375 |
0; 0; 1; 1; 3; 2 | — |
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
Data sourced from ClinicalTrials.gov (NCT03334851). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.