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

Rheumatoid Arthritis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02089087
• Other study ID #: CCFZ533X2101
• Status: Completed
• Phase: Phase 1
• Start date: January 7, 2013
• Est. completion date: February 3, 2017

Study information

• Verified date: March 2019
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: February 3, 2017
• Est. primary completion date: February 3, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria (for healthy volunteers):

1. 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)

2. Vital signs (systolic and diastolic blood pressure and pulse rate) should be within normal limits

3. Weight 50-150 kg and a body mass index (BMI) 18-32 kg/m2

Inclusion Criteria (for rheumatoid arthritis patients):

1. Healthy male and surgically sterilized or post-menopausal female subjects 18 to 55 years of age

2. Fulfilled 2010 ACR/EULAR classification criteria for RA per Investigator

3. Treatment with a stable oral RA treatment regimen for = 4 weeks before randomization

4. Systemic corticosteroids allowed if on a stable dose (= 10 mg/day of prednisone or equivalent) = 4 weeks prior to randomization

5. 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):

1. History of hypersensitivity to vaccines, the study drug, or to drugs of similar chemical classes (i.e., biologic agents)

2. Abnormal hematology, coagulation or inflammatory lab results

3. History or evidence of tuberculosis.

Exclusion Criteria (for rheumatoid arthritis patients):

1. Use of anti-TNF or other biologics in previous 3 months

2. Any intra-articular injection therapy (e.g., corticosteroid, hyaluronan) required for treatment of acute RA flare within 4 weeks before randomization

3. Previous treatment with a B cell-depleting biologic agent or any other immunomodulatory biologic agent within 5 half-lives (experimental or approved)

4. Current treatment with cyclophosphamide

5. Autoimmune disease other than RA

6. Adult juvenile rheumatoid arthritis

7. RA functional status class IV according to the ACR 1991 revised criteria Other protocol-defined inclusion/exclusion criteria may apply

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Biological:
• CFZ533
Single dose at varying dosage levels depending on treatment assignment

Drug:
• Placebo

Locations

Country	Name	City	State
Taiwan	Novartis Investigative Site	Taipei
United States	Novartis Investigative Site	Anniston	Alabama
United States	Novartis Investigative Site	Duncansville	Pennsylvania
United States	Novartis Investigative Site	Lincoln	Nebraska
United States	Novartis Investigative Site	Miami	Florida
United States	Novartis Investigative Site	South Miami	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients with adverse events as a measure of safety and tolerability		7 months
Secondary	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	6 months
Secondary	Plasma Pharmacokinetics (PK) of CFZ533: Observed Maximum Plasma Concentration Following Drug Administration (Cmax)		6 months
Secondary	Plasma Pharmacokinetics (PK) of CFZ533: Systemic Clearance from Plasma (CL)		6 months
Secondary	Plasma Pharmacokinetics (PK) of CFZ533: Apparent Volume of Distribution (Vss)		6 months
Secondary	CFZ533 immunogenicity	Determining the presence and measuring amount of anti-CFZ533 antibodies in the blood	6 months

External Links

•   A Plain Language Trial Summary is available on novartisclinicaltrials.com
•   Results for CCFZ533X2101 from the Novartis Trial Results database