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Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Dose CFZ533 in Rheumatoid Arthritis Patients

Primary Purpose

Rheumatoid Arthritis

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

CFZ533

Placebo

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring Rheumatoid arthritis, RA, first-in-human, single ascending dose, safety, tolerability

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria (for healthy volunteers):

Healthy male and surgically sterilized or post-menopausal female subjects 18 to 55 years of age (for Cohort 9 only, subjects must be of Chinese descent)
Vital signs (systolic and diastolic blood pressure and pulse rate) should be within normal limits
Weight 50-150 kg and a body mass index (BMI) 18-32 kg/m2

Inclusion Criteria (for rheumatoid arthritis patients):

Healthy male and surgically sterilized or post-menopausal female subjects 18 to 55 years of age
Fulfilled 2010 ACR/EULAR classification criteria for RA per Investigator
Treatment with a stable oral RA treatment regimen for ≥ 4 weeks before randomization
Systemic corticosteroids allowed if on a stable dose (≤ 10 mg/day of prednisone or equivalent) ≥ 4 weeks prior to randomization
Subjects taking NSAIDs (COX-1 or COX-2 inhibitors) as part of their RA therapy must be on a stable dose for at least 4 weeks before randomization

Exclusion Criteria (for healthy volunteers):

History of hypersensitivity to vaccines, the study drug, or to drugs of similar chemical classes (i.e., biologic agents)
Abnormal hematology, coagulation or inflammatory lab results
History or evidence of tuberculosis.

Exclusion Criteria (for rheumatoid arthritis patients):

Use of anti-TNF or other biologics in previous 3 months
Any intra-articular injection therapy (e.g., corticosteroid, hyaluronan) required for treatment of acute RA flare within 4 weeks before randomization
Previous treatment with a B cell-depleting biologic agent or any other immunomodulatory biologic agent within 5 half-lives (experimental or approved)
Current treatment with cyclophosphamide
Autoimmune disease other than RA
Adult juvenile rheumatoid arthritis
RA functional status class IV according to the ACR 1991 revised criteria

Other protocol-defined inclusion/exclusion criteria may apply

Sites / Locations

Novartis Investigative Site
Novartis Investigative Site
Novartis Investigative Site
Novartis Investigative Site
Novartis Investigative Site
Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Arm Label

CFZ533 in healthy volunteers

CFZ533 in rheumatoid arthritis patients

Placebo

Arm Description

CFZ533 single dose in healthy volunteers

CFZ533 single dose in rheumatoid arthritis patients

Placebo single dose

Outcomes

Primary Outcome Measures

Number of patients with adverse events as a measure of safety and tolerability

Secondary Outcome Measures

Plasma Pharmacokinetics (PK) of CFZ533: Area Under the Plasma Concentration-time Curve (AUC)

The following PK parameters were determined from the plasma concentration time profile of CFZ533 using a non-compartmental method: AUCtau: Area under the plasma concentration-time curve from time zero to the end of the dosing interval AUClast: Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration AUCinf: Area under the plasma concentration-time curve from time zero to infinity

Plasma Pharmacokinetics (PK) of CFZ533: Observed Maximum Plasma Concentration Following Drug Administration (Cmax)

Plasma Pharmacokinetics (PK) of CFZ533: Systemic Clearance from Plasma (CL)

Plasma Pharmacokinetics (PK) of CFZ533: Apparent Volume of Distribution (Vss)

CFZ533 immunogenicity

Determining the presence and measuring amount of anti-CFZ533 antibodies in the blood

Full Information

NCT ID

NCT02089087

First Posted

March 13, 2014

Last Updated

December 9, 2020

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT02089087

Brief Title

Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Dose CFZ533 in Rheumatoid Arthritis Patients

Official Title

A Randomized, Double-blind, Placebo-controlled, Single Ascending Dose First-in-human Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of CFZ533 in Healthy Subjects and Rheumatoid Arthritis Patients

Study Type

Interventional

2. Study Status

Record Verification Date

March 2019

Overall Recruitment Status

Completed

Study Start Date

January 7, 2013 (Actual)

Primary Completion Date

February 3, 2017 (Actual)

Study Completion Date

February 3, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

This is a first-in-human study to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single intravenous and subcutaneous doses of CFZ533 in healthy subjects and intravenous doses in rheumatoid arthritis patients.

Detailed Description

This was a Healthy Volunteer only study originally, but after an amendment to protocol, rheumatoid arthritis patients will be starting 7-Mar-2014 and thus, the protocol is now registered.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Rheumatoid Arthritis

Keywords

Rheumatoid arthritis, RA, first-in-human, single ascending dose, safety, tolerability

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

75 (Actual)

8. Arms, Groups, and Interventions

Arm Title

CFZ533 in healthy volunteers

Arm Type

Experimental

Arm Description

CFZ533 single dose in healthy volunteers

Arm Title

CFZ533 in rheumatoid arthritis patients

Arm Type

Experimental

Arm Description

CFZ533 single dose in rheumatoid arthritis patients

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo single dose

Intervention Type

Biological

Intervention Name(s)

CFZ533

Intervention Description

Single dose at varying dosage levels depending on treatment assignment

Intervention Type

Drug

Intervention Name(s)

Placebo

Primary Outcome Measure Information:

Title

Number of patients with adverse events as a measure of safety and tolerability

Time Frame

7 months

Secondary Outcome Measure Information:

Title

Plasma Pharmacokinetics (PK) of CFZ533: Area Under the Plasma Concentration-time Curve (AUC)

Description

Time Frame

6 months

Title

Plasma Pharmacokinetics (PK) of CFZ533: Observed Maximum Plasma Concentration Following Drug Administration (Cmax)

Time Frame

6 months

Title

Plasma Pharmacokinetics (PK) of CFZ533: Systemic Clearance from Plasma (CL)

Time Frame

6 months

Title

Plasma Pharmacokinetics (PK) of CFZ533: Apparent Volume of Distribution (Vss)

Time Frame

6 months

Title

CFZ533 immunogenicity

Description

Determining the presence and measuring amount of anti-CFZ533 antibodies in the blood

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria (for healthy volunteers): Healthy male and surgically sterilized or post-menopausal female subjects 18 to 55 years of age (for Cohort 9 only, subjects must be of Chinese descent) Vital signs (systolic and diastolic blood pressure and pulse rate) should be within normal limits Weight 50-150 kg and a body mass index (BMI) 18-32 kg/m2 Inclusion Criteria (for rheumatoid arthritis patients): Healthy male and surgically sterilized or post-menopausal female subjects 18 to 55 years of age Fulfilled 2010 ACR/EULAR classification criteria for RA per Investigator Treatment with a stable oral RA treatment regimen for ≥ 4 weeks before randomization Systemic corticosteroids allowed if on a stable dose (≤ 10 mg/day of prednisone or equivalent) ≥ 4 weeks prior to randomization Subjects taking NSAIDs (COX-1 or COX-2 inhibitors) as part of their RA therapy must be on a stable dose for at least 4 weeks before randomization Exclusion Criteria (for healthy volunteers): History of hypersensitivity to vaccines, the study drug, or to drugs of similar chemical classes (i.e., biologic agents) Abnormal hematology, coagulation or inflammatory lab results History or evidence of tuberculosis. Exclusion Criteria (for rheumatoid arthritis patients): Use of anti-TNF or other biologics in previous 3 months Any intra-articular injection therapy (e.g., corticosteroid, hyaluronan) required for treatment of acute RA flare within 4 weeks before randomization Previous treatment with a B cell-depleting biologic agent or any other immunomodulatory biologic agent within 5 half-lives (experimental or approved) Current treatment with cyclophosphamide Autoimmune disease other than RA Adult juvenile rheumatoid arthritis RA functional status class IV according to the ACR 1991 revised criteria Other protocol-defined inclusion/exclusion criteria may apply

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Novartis Investigative Site

City

Anniston

State/Province

Alabama

ZIP/Postal Code

36207-5710

Country

United States

Facility Name

Novartis Investigative Site

City

Miami

State/Province

Florida

ZIP/Postal Code

33136

Country

United States

Facility Name

Novartis Investigative Site

City

South Miami

State/Province

Florida

ZIP/Postal Code

33143

Country

United States

Facility Name

Novartis Investigative Site

City

Lincoln

State/Province

Nebraska

ZIP/Postal Code

68502

Country

United States

Facility Name

Novartis Investigative Site

City

Duncansville

State/Province

Pennsylvania

ZIP/Postal Code

16635

Country

United States

Facility Name

Novartis Investigative Site

City

Taipei

ZIP/Postal Code

110

Country

Taiwan

12. IPD Sharing Statement

Citations:

PubMed Identifier

31647605

Citation

Espie P, He Y, Koo P, Sickert D, Dupuy C, Chokote E, Schuler R, Mergentaler H, Ristov J, Milojevic J, Verles A, Groenewegen A, Auger A, Avrameas A, Rotte M, Colin L, Tomek CS, Hernandez-Illas M, Rush JS, Gergely P. First-in-human clinical trial to assess pharmacokinetics, pharmacodynamics, safety, and tolerability of iscalimab, an anti-CD40 monoclonal antibody. Am J Transplant. 2020 Feb;20(2):463-473. doi: 10.1111/ajt.15661. Epub 2019 Dec 6.

Results Reference

derived

Links:

URL

https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=16987

Description

Results for CCFZ533X2101 from the Novartis Trial Results database

URL

https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=283

Description

A Plain Language Trial Summary is available on novartisclinicaltrials.com

Learn more about this trial

Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Dose CFZ533 in Rheumatoid Arthritis Patients

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