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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Biological: CFZ533
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CFZ533 in healthy volunteers<br>CFZ533 single dose in healthy volunteers | Biological: CFZ533<br>* Single dose at varying dosage levels depending on treatment assignment<br>|
| Experimental: CFZ533 in rheumatoid arthritis patients<br>CFZ533 single dose in rheumatoid arthritis patients | Biological: CFZ533<br>* Single dose at varying dosage levels depending on treatment assignment<br>|
| Placebo Comparator: Placebo<br>Placebo single dose | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with adverse events as a measure of safety and tolerability |  | 7 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Plasma Pharmacokinetics (PK) of CFZ533: Observed Maximum Plasma Concentration Following Drug Administration (Cmax) |  | 6 months | 
| Plasma Pharmacokinetics (PK) of CFZ533: Systemic Clearance from Plasma (CL) |  | 6 months | 
| Plasma Pharmacokinetics (PK) of CFZ533: Apparent Volume of Distribution (Vss) |  | 6 months | 
| CFZ533 immunogenicity | Determining the presence and measuring amount of anti-CFZ533 antibodies in the blood | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid arthritis, RA, first-in-human, single ascending dose, safety, tolerability