Clinical trial NCT02089087: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid arthritis, RA, first-in-human, single ascending dose, safety, tolerability
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2014-03-17
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Number of patients with adverse events as a measure of safety and tolerability
timeFrame: 7 months
Secondary outcomes:
measure: Plasma Pharmacokinetics (PK) of CFZ533: Area Under the Plasma Concentration-time Curve (AUC)
timeFrame: 6 months
measure: Plasma Pharmacokinetics (PK) of CFZ533: Observed Maximum Plasma Concentration Following Drug Administration (Cmax)
timeFrame: 6 months
measure: Plasma Pharmacokinetics (PK) of CFZ533: Systemic Clearance from Plasma (CL)
timeFrame: 6 months
measure: Plasma Pharmacokinetics (PK) of CFZ533: Apparent Volume of Distribution (Vss)
timeFrame: 6 months
measure: CFZ533 immunogenicity
timeFrame: 6 months
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Novartis Investigative Site
state: Alabama
city: Miami
country: United States
facility: Novartis Investigative Site
state: Florida
city: South Miami
country: United States
facility: Novartis Investigative Site
state: Florida
city: Lincoln
country: United States
facility: Novartis Investigative Site
state: Nebraska
city: Duncansville
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
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.