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

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02089087
• Collaborator: (none)
• Enrollment: 75
• Locations: 6
• Arms: 3
• Actual Duration (Months): 48.9
• Patients Per Site: 12.5
• Patients Per Site Per Month: 0.3

Study Details

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
• 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: Jan 7, 2013
• Actual Primary Completion Date: Feb 3, 2017
• Actual Study Completion Date: Feb 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 [7 months]

Secondary Outcome Measures

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

3. Plasma Pharmacokinetics (PK) of CFZ533: Systemic Clearance from Plasma (CL) [6 months]

4. Plasma Pharmacokinetics (PK) of CFZ533: Apparent Volume of Distribution (Vss) [6 months]

5. CFZ533 immunogenicity [6 months]

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

Eligibility Criteria

Criteria

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

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

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Anniston	Alabama	United States	36207-5710
2	Novartis Investigative Site	Miami	Florida	United States	33136
3	Novartis Investigative Site	South Miami	Florida	United States	33143
4	Novartis Investigative Site	Lincoln	Nebraska	United States	68502
5	Novartis Investigative Site	Duncansville	Pennsylvania	United States	16635
6	Novartis Investigative Site	Taipei		Taiwan	110

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02089087
• Other Study ID Numbers: CCFZ533X2101
• First Posted: Mar 17, 2014
• Last Update Posted: Dec 11, 2020
• Last Verified: Mar 1, 2019

• Keywords provided by Novartis Pharmaceuticals: Rheumatoid arthritis, RA, first-in-human, single ascending dose, safety, tolerability
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid

Study Results

No Results Posted as of Dec 11, 2020