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

• ClinicalTrials.gov Identifier: NCT02089087
• Recruitment Status: Completed
• First Posted: March 17, 2014
• Last Update Posted: December 11, 2020
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

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.

Condition or disease	Intervention/treatment	Phase
Rheumatoid Arthritis	Biological: CFZ533; Drug: Placebo	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 75 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: January 7, 2013
• Actual Primary Completion Date: February 3, 2017
• Actual Study Completion Date: February 3, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: CFZ533 in healthy volunteers; CFZ533 single dose in healthy volunteers	Biological: CFZ533; Single dose at varying dosage levels depending on treatment assignment
Experimental: CFZ533 in rheumatoid arthritis patients; CFZ533 single dose in rheumatoid arthritis patients	Biological: CFZ533; Single dose at varying dosage levels depending on treatment assignment
Placebo Comparator: Placebo; Placebo single dose	Drug: Placebo

Outcome Measures

Primary Outcome Measures :

1. Number of patients with adverse events as a measure of safety and tolerability [ Time Frame: 7 months ]

Secondary Outcome Measures :

1. Plasma Pharmacokinetics (PK) of CFZ533: Area Under the Plasma Concentration-time Curve (AUC) [ Time Frame: 6 months ]

   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

2. Plasma Pharmacokinetics (PK) of CFZ533: Observed Maximum Plasma Concentration Following Drug Administration (Cmax) [ Time Frame: 6 months ]
3. Plasma Pharmacokinetics (PK) of CFZ533: Systemic Clearance from Plasma (CL) [ Time Frame: 6 months ]
4. Plasma Pharmacokinetics (PK) of CFZ533: Apparent Volume of Distribution (Vss) [ Time Frame: 6 months ]
5. CFZ533 immunogenicity [ Time Frame: 6 months ]
   Determining the presence and measuring amount of anti-CFZ533 antibodies in the blood

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

United States, Alabama

Novartis Investigative Site

Anniston, Alabama, United States, 36207-5710

United States, Florida

Novartis Investigative Site

Miami, Florida, United States, 33136

Novartis Investigative Site

South Miami, Florida, United States, 33143

United States, Nebraska

Novartis Investigative Site

Lincoln, Nebraska, United States, 68502

United States, Pennsylvania

Novartis Investigative Site

Duncansville, Pennsylvania, United States, 16635

Taiwan

Novartis Investigative Site

Taipei, Taiwan, 110

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

Additional Information:

Results for CCFZ533X2101 from the Novartis Trial Results database 

A Plain Language Trial Summary is available on novartisclinicaltrials.com 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Espié P, He Y, Koo P, Sickert D, Dupuy C, Chokoté 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.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02089087
• Other Study ID Numbers: CCFZ533X2101
• First Posted: March 17, 2014
• Last Update Posted: December 11, 2020
• Last Verified: March 2019

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

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

Additional relevant MeSH terms:

Arthritis; Arthritis, Rheumatoid; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases