A Study To Assess The Safety Of PF-06342674 In Adults With Type 1 Diabetes

NCT02038764 | Completed Phase 1 Results FDA Drug

• 1 other identifier: B4351003
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 21

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and immunogenicity of multiple doses of PF-06342674. Several dose levels will be evaluated.

Conditions

Diabetes Mellitus, Type 1

Keywords

Phase 1; RN168; Adults; Type 1 Diabetes; T1D

Outcome Measures

Primary Outcomes (13)

• Number of Participants With Dose Limiting or Intolerable Treatment Related Adverse Events (AEs)

  Number of participants with dose limiting or intolerable treatment related adverse events (AEs) was reported. An AE was any untoward medical occurrence in a clinical investigation subject administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage.

  Day 1 through Day 127

• Number of Participants With All-Causality Treatment Emergent Adverse Events(TEAEs)

  Number of participants with all-causality treatment emergent adverse events were reported. An AE was any untoward medical occurrence in a clinical investigation subject administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were those AEs with initial onset or increasing in severity after the first dose of study drug. TEAEs included both serious and non-serious AE

  Day 1 through Day 127

• Number of Participants With Treatment-Related TEAEs

  Number of participants with treatment-related TEAEs were reported. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An AE was any untoward medical occurrence in a clinical investigation subject administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were those AEs with initial onset or increasing in severity after the first dose of study drug.

  Day 1 through Day 127

• Number of Participants With All-Causality TEAEs Listed by Common Terminology Criteria for Adverse Events (CTCAE) Grade

  TEAEs were those AEs with initial onset or increasing in severity after the first dose of study drug. CTCAE version 4.03 was used to grade the severity of TEAEs. Grade 1 referred to mild AEs; Grade 2 referred to moderate AEs; Grade 3 referred to severe AEs; Grade 4 referred to AEs with life-threatening consequences, and urgent intervention was needed to manage them; Grade 5 referred to death related to AE.

  Day 1 through Day 127

• Number of Participants With All-Causality Treatment-Emergent Hypoglycemic Adverse Events

  Number of participants with all-causality treatment-emergent hypoglycemic adverse events was reported. Any blood glucose values less than(\<)55 mg/dL with or without symptoms was reported as adverse events of hypoglycemia.

  Day 1 through Day 127

• Number of Participants With All-Causality Treatment-Emergent Hypoglycemic Adverse Events Listed by CTCAE Grade

  Any blood glucose values \<55 mg/dL with or without symptoms was reported as adverse events of hypoglycemia. CTCAE version 4.03 was used to grade the severity of TEAEs. Grade 1 referred to mild AEs; Grade 2 referred to moderate AEs; Grade 3 referred to severe AEs; Grade 4 referred to AEs with life-threatening consequences, and urgent intervention was needed to manage them; Grade 5 referred to death related to AE.

  Day 1 through Day 127

• Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)

  The following laboratory test parameters were evaluated in this study: hematology (hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, absolute total neutrophils, absolute eosinophils, absolute basophils, absolute monocytes, and absolute lymphocytes),coagulation (partial thromboplastin time, prothrombin, and prothrombin international ratio), liver function(total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total protein, and albumin), renal function (blood urea nitrogen, creatinine, and uric acid), electrolytes (sodium, potassium, chloride, calcium, and venous bicarbonate), clinical chemistry(glucose, glycosylated, and hemoglobin), and urinalysis (pH, qualitative glucose, qualitative protein, qualitative blood, urobilinogen, qualitative bilirubin, nitrites, leukocyte, esterase and microscopy).

  Day 1 through Day 127

• Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Absolute Values)

  Number of participants with vital signs data of absolute values meeting criteria of potential clinical concern. Absolute values were analyzed for systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse rate. Number of participants with vital signs data meeting the following criteria was reported: Criterion A: SBP \<90 millimeter of mercury(mmHg); Criterion B: DBP \<50 mmHg; Criterion C: pulse rate \< 40 beats per minute(BPM); Criterion D: pulse rate \>120 BPM

  Day 1 through Day 127

• Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Decreases From Baseline)

  The number of participants with vital signs data of maximum decrease from baseline meeting the following criteria was reported: Criterion A: maximum decrease from baseline in systolic BP \>= 30 mmHg; Criterion B: maximum decrease from baseline in diastolic BP \>=20 mmHg

  Day 1 through Day 127

• Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Increases From Baseline)

  The number of participants with vital signs data of maximum increase from baseline meeting the following criteria was reported: Criterion A: maximum increase from baseline in systolic BP \>= 30 mmHg; Criterion B: maximum increase from baseline in diastolic BP \>= 20 mmHg

  Day 1 through Day 127

• Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Absolute Value)

  The number of participants with ECG absolute values meeting the following criteria was reported: Criterion A: maximum PR interval (time from the beginning of P wave to the start of QRS complex, corresponding to the end of atrial depolarization and onset of ventricular depolarization) \>=300 msec; Criterion B: maximum QRS complex(time from Q wave to the end of S wave, corresponding to ventricle depolarization) \>=200 msec; Criterion C: maximum QTcF interval (time from the beginning of Q wave to the end of T wave corresponding to electrical systole, corrected for heart rate using Fridericia's formula) 450-\<480 msec; Criterion D: maximum QTcF interval 480-\<500 msec; Criterion E: maximum QTcF interval (Fridericia's correction) \>=500 msec

  Day 1 through Day 127

• Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Increases From Baseline)

  Number of participants with ECG meeting the following criteria was reported: Criterion A: maximum PR interval increase from baseline percentage change (PctChg)\>= 25/50%; Criterion B: maximum QRS complex increase from baseline PctChg \>= 25/50%; Criterion C: maximum QTcF interval increase from baseline 30\<=change\<60 msec; Criterion D: maximum QTcF interval increase from baseline change \>=60 msec.

  Day 1 through Day 127

• Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit

  Number of participants with serum anti-PF-06342674 antibody response to the intramuscular tetanus vaccine was reported. Positive Anti-PF-06342674 Antibody response is defined as anti-tetanus toxoid immunoglobulin G (IgG) titer value \>=100

  Day 1, Day 15, Day 29, Day 57, Day 85, and Day127 and follow-up visits

Secondary Outcomes (7)

• Area Under Concentration-Time Curve From Time Zero to Time Tau(AUCtau) on Day 1 and Day 71

  0,1,4 hours post-dose on Day 1 and Day 71

• Apparent Oral Clearance (CL/F) on Day 71

  0,1,4 hours post-dose on Day 71

• Maximum Observed Plasma Concentration (Cmax) on Day 1 and Day 71

  0, 1, 4 hours post-dose on Day 1 and Day 71

• Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1 and Day 71

  0, 1, 4 hours post-dose on Day 1 and Day 71

• Plasma Decay Half-Life (t1/2) on Day 71

  0, 1, 4 hours post-dose on Day 71

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

PF-06342674

EXPERIMENTAL

Biological: PF-06342674 Dose A; Biological: PF-06342674 Dose B; Biological: PF-06342674 Dose C; Biological: PF-06342674 Dose D

Interventions

Placebo DRUG

Placebo

Placebo

PF-06342674 Dose A BIOLOGICAL

Multiple SC Doses

PF-06342674

PF-06342674 Dose B BIOLOGICAL

Multiple SC Doses

PF-06342674

PF-06342674 Dose C BIOLOGICAL

Multiple SC Doses

PF-06342674

PF-06342674 Dose D BIOLOGICAL

Multiple SC Doses

PF-06342674

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women and men age 18 and older.
• Diagnosis of type 1 diabetes within 2 years of randomization.
• Peak stimulated C-peptide levels ≥ 0.15 ng/mL.

You may not qualify if:

• Anticipated ongoing use of diabetes medications other than insulin.
• Evidence or history of diabetic complications with significant end-organ damage.
• Episode of severe hypoglycemia within 60 days of randomization.
• Multiple hospitalizations for diabetic ketoacidosis.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (21)

VA San Diego Healthcare System (Drug Shipment)

San Diego, California, 92161, United States

Location

Veterans Administration San Diego Healthcare System

San Diego, California, 92161, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Barbara Davis Center

Aurora, Colorado, 80045, United States

Location

Yale School of Medicine

New Haven, Connecticut, 06510, United States

Location

Yale New Haven Hospital - Investigational Drug Services

New Haven, Connecticut, 06511, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06519, United States

Location

Atlanta Diabetes Associates

Atlanta, Georgia, 30318, United States

Location

Duchossois Center for Advanced Medicine

Chicago, Illinois, 60637, United States

Location

The University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

University of Chicago Clinical Resource Center

Chicago, Illinois, 60637, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Umass Memorial Medical Center

Worcester, Massachusetts, 01655, United States

Location

University of Massachusetts Medical School

Worcester, Massachusetts, 01655, United States

Location

University Of Minnesota Fairview Pharmacy Services

Minneapolis, Minnesota, 55454, United States

Location

University Of Minnesota Medical School

Minneapolis, Minnesota, 55455, United States

Location

Barnes- Jewish HOSP Att: Kathryn Vehe

St Louis, Missouri, 63110, United States

Location

Washington University - Center for Advanced Medicine

St Louis, Missouri, 63110, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Duke Clinical Research Unit

Durham, North Carolina, 27710, United States

Location

Duke University Health Systems (DUHS) Investigational Drug Services

Durham, North Carolina, 27710, United States

Location

Related Publications (1)

• Herold KC, Bucktrout SL, Wang X, Bode BW, Gitelman SE, Gottlieb PA, Hughes J, Joh T, McGill JB, Pettus JH, Potluri S, Schatz D, Shannon M, Udata C, Wong G, Levisetti M, Ganguly BJ, Garzone PD; RN168 Working Group. Immunomodulatory activity of humanized anti-IL-7R monoclonal antibody RN168 in subjects with type 1 diabetes. JCI Insight. 2019 Dec 19;4(24):e126054. doi: 10.1172/jci.insight.126054.

  PMID: 31852846 DERIVED

Related Links

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

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2014
• First Posted: January 17, 2014
• Study Start: June 4, 2014
• Primary Completion: September 13, 2016
• Study Completion: September 13, 2016
• Last Updated: August 3, 2018
• Results First Posted: August 3, 2018

Record last verified: 2017-10

Locations

US (21)