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

Study at a glance

From the registry record, last updated by the sponsor on 30 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

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

ClinicalTrials.gov ID

NCT03334851

Acronym / sponsor ID

C1131001

Conditions

Systemic Lupus Erythematosus, Rheumatoid Arthritis

Phase

Phase 1

Study type

Interventional

Recruitment status

Completed

Enrolment

74 participants (actual)

Lead sponsor

PfizerIndustry (pharma, biotech, devices)

Study start

17 Nov 2017 (actual)

Primary completion

15 Feb 2022 (actual)

Study completion

15 Feb 2022 (actual)

First posted

7 Nov 2017 (actual)

Results

Posted 30 Oct 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose

Basic science

Allocation

Randomised

Intervention model

Sequential

Masking

Quadruple blind (participant, care provider, investigator, outcomes assessor)

Number of arms

14

Who may qualify

Ages

18 to 70 years

Sex

All

Healthy volunteers

Not accepted

Age groups

Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Primary outcome

1. Number of Participants With Dose-Limiting Toxicity (DLT)

   Time frame: 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)

   DLT was defined as any of the following events meeting the criteria: (1) >=2 participants within a dose cohort developed Common Terminology Criteria for Adverse Events (CTCAE) v4.0 Grade 3 adverse event considered to be serious in the same organ system or 1 participant developed a CTCAE v4.0 Grade 4 or higher SAE considered related to study drug; (2) 50% or more participants within a dose cohort experienced a CTCAE v4.0 Grade 3 or higher infusion reaction; (3) a confirmed or probable case of Progressive Multifocal Leukoencephalopathy was observed; (4) the mean exposure for the treatment group reached or exceeded the exposure stopping limit of Cav of 261 mg/mL, or, based on the observed data, the group mean Cav of the next planned dose was projected to exceed the exposure stopping limit. Cav = average serum concentration.

2. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity

   Time frame: 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)

   An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Relatedness to study drug was assessed by the investigator. Treatment-emergent were events between first dose of study drug and up to approximately Week 40 that were absent before treatment or that worsened relative to pretreatment state. AEs are classified according to the severity in 3 categories a) mild - AEs does not interfere with participant's usual function b) moderate - AEs interferes to some extent with participant's usual function c) severe - AEs interferes significantly with participant's usual function.

3. Number of Participants With All-Causality and Treatment-Related TEAEs

   Time frame: 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)

   An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Relatedness to study drug was assessed by the investigator. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to approximately Week 40 that were absent before treatment or that worsened relative to pretreatment state.

4. Number of Participants With Permanent Discontinuation Due to TEAEs

   Time frame: 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)

   An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent were events between first dose of study drug and up to approximately Week 40 that were absent before treatment or that worsened relative to pretreatment state.

5. Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis

   Time frame: 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)

   Hematology included hemoglobin, hematocrit, red blood cell, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet and white blood cell count, total neutrophils, eosinophils, monocytes, basophils and lymphocytes. Chemistry included blood urea nitrogen, creatinine, glucose, calcium, sodium, potassium, chloride, bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid, albumin, total protein and creatine kinase. Urinalysis included pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, urobilinogen, urine bilirubin, microscopy and creatinine. Clinical significance was judged by the investigator and those met the criteria of AE are listed here. Clinically significant laboratory abnormalities reported for at least 1 participant in the whole study are presented here. Baseline was the last pre-dose measurement (first treatment for MAD cohorts).

6. Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria

   Time frame: 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)

   Criteria for abnormality in vital signs: supine pulse rate <40 beats per minute (bpm) or >120 bpm; standing pulse rate <40 bpm or >120 bpm; sitting systolic blood pressure (BP) <90 mmHg, maximum increase or decrease from baseline of >=30 mmHg; sitting diastolic BP <50 mmHg, maximum increase or decrease from baseline of >=20 mmHg. Baseline was defined as the last pre-dose measurement in Day 1. Only those categories in which at least 1 participant had data were reported.

7. Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria

   Time frame: 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)

   ECG abnormalities criteria included: 1) maximum QTc interval (ms): 450<= QTc <480, 480<= QTc <500, and QTc >=500; QTc maximum increase from baseline (ms): 30<= change <60, and change >=60; 2) maximum PR interval (ms): >=300; PR increase from baseline (ms): baseline >200 with 25% increase at maximum, baseline <=200 with 50% increase at maximum; 3) maximum QRS (ms): >=140; QRS increase from baseline (ms) >=50%. QTcF indicates QT interval corrected using the Fridericia's formula. QTcB indicates QT interval corrected using the Bazett's formula. Baseline was defined as the average of the triplicate pre-dose recordings at Day 1. Only those categories in which at least 1 participant had data were reported.

8. Number of Participants With All-Causality and Treatment-Related Infections and Infestations

   Time frame: 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)

   An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Relatedness to study drug was assessed by the investigator. The incidence of AEs by system organ class "infections and infestations" was reported here.

Results and safety

Loading the posted results from ClinicalTrials.gov…

Research links

• Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2023.
• Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
• Derived from this study: PubMed 38845046Cohen S, Beebe JS, Chindalore V, Guan S, Hassan-Zahraee M, Saxena M, Xi L, Hyde C, Koride S, Levin R, Lubaczewski S, Salganik M, Sloan A, Stevens E, Peeva E, Vincent MS, Martin DA, Chu M. A Phase 1, randomized, double-blind, placebo-controlled, single- and multiple-dose escalation study to evaluate the safety and pharmacokinetics/pharmacodynamics of PF-06835375, a C-X-C chemokine receptor type 5 directed antibody, in patients with systemic lupus erythematosus or rheumatoid arthritis. Arthritis Res Ther. 2024 Jun 6;26(1):117. doi: 10.1186/s13075-024-03337-2.
• To obtain contact information for a study center near you, click here.Link provided by the sponsor.
• Individual participant dataSharing planned: No. 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

17 sites in 1 country: see every site and its status.