First-in-man Trial of NNC0142-0002 in Patients With Rheumatoid Arthritis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT00927927
First received: June 24, 2009
Last updated: October 21, 2013
Last verified: October 2013
  Purpose

This trial is conducted in Europe. The aim of this clinical trial is to investigate the safety, tolerability, pharmacokinetic (the effect of the body on the investigated drug) and signs of clinical efficacy of increasing single doses or four repeated doses of NNC 0142-0002 in patients with rheumatoid arthritis.


Condition Intervention Phase
Inflammation
Rheumatoid Arthritis
Drug: NNC0142-0002
Drug: placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled, Dose-escalation, Single and Multiple Dose Trial to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of NNC0142-0002 Administered Subcutaneously to Subjects With Rheumatoid Arthritis

Resource links provided by NLM:


Further study details as provided by Novo Nordisk A/S:

Primary Outcome Measures:
  • Frequency of Adverse Events [ Time Frame: Adverse events were collected for a mean (min; max) of 15.7 (6.4; 42.6) weeks for single-dose subjects, and 30.6 (12.7; 43.1) for multiple-dose subjects. Visits were scheduled until receptor occupancy was below the cut-off level for receptor positivity. ] [ Designated as safety issue: No ]

    Adverse event: any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product, and which does not necessarily have a causal relationship with this treatment.

    Serious AE: AE that at any dose level resulted in any of the following: death, a life-threatening experience, in-subject hospitalization/prolongation of existing hospitalization, a persistent/significant disability/incapacity, a congenital anomaly or birth defect, or an important medical event that may jeopardize the subject and require medical or surgical intervention.



Secondary Outcome Measures:
  • Area Under the Concentration-time Curve (AUC) [ Time Frame: Data were collected from 0 hours to at least Day 43 (SD cohorts) and Day 85 (MD cohorts), and until the receptor occupancy was confirmed below the cut-off level for receptor positivity. ] [ Designated as safety issue: No ]
    Systemic exposure to NNC0142-0002.


Enrollment: 65
Study Start Date: June 2009
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SD 0.0002 mg/kg
Subjects were injected once with NNC0142-0002 at a dose of 0.0002 mg/kg
Drug: NNC0142-0002
Single dose, ranging from 0.0002 mg/kg up to max 7.5 mg/kg, administered subcutaneously (under the skin) on day 1
Experimental: SD 0.0012 mg/kg
Subjects were injected once with NNC0142-0002 at a dose of 0.0012 mg/kg
Drug: NNC0142-0002
Single dose, ranging from 0.0002 mg/kg up to max 7.5 mg/kg, administered subcutaneously (under the skin) on day 1
Experimental: SD 0.007 mg/kg
Subjects were injected once with NNC0142-0002 at a dose of 0.007 mg/kg
Drug: NNC0142-0002
Single dose, ranging from 0.0002 mg/kg up to max 7.5 mg/kg, administered subcutaneously (under the skin) on day 1
Experimental: SD 0.035 mg/kg
Subjects were injected once with NNC0142-0002 at a dose of 0.035 mg/kg
Drug: NNC0142-0002
Single dose, ranging from 0.0002 mg/kg up to max 7.5 mg/kg, administered subcutaneously (under the skin) on day 1
Experimental: SD 0.175 mg/kg
Subjects were injected once with NNC0142-0002 at a dose of 0.175 mg/kg
Drug: NNC0142-0002
Single dose, ranging from 0.0002 mg/kg up to max 7.5 mg/kg, administered subcutaneously (under the skin) on day 1
Experimental: SD 0.7 mg/kg
Subjects were injected once with NNC0142-0002 at a dose of 0.7 mg/kg
Drug: NNC0142-0002
Single dose, ranging from 0.0002 mg/kg up to max 7.5 mg/kg, administered subcutaneously (under the skin) on day 1
Experimental: SD 2.5 mg/kg
Subjects were injected once with NNC0142-0002 at a dose of 2.5 mg/kg
Drug: NNC0142-0002
Single dose, ranging from 0.0002 mg/kg up to max 7.5 mg/kg, administered subcutaneously (under the skin) on day 1
Experimental: SD 7.5 mg/kg
Subjects were injected once with NNC0142-0002 at a dose of 7.5 mg/kg
Drug: NNC0142-0002
Single dose, ranging from 0.0002 mg/kg up to max 7.5 mg/kg, administered subcutaneously (under the skin) on day 1
Experimental: SD Placebo
Subjects were injected once with placebo
Drug: placebo
Single dose of 0 mg/kg administered subcutaneously (under the skin); cohort 1-7b on day 1, cohort 8-11 biweekly four times
Experimental: MD 0.02 mg/kg
Subjects were injected biweekly four times with NNC0142-0002 at a dose of 0.02 mg/kg
Drug: NNC0142-0002
Multiple dose, ranging from 0.02 mg/kg up to max 4.0 mg/kg, administered subcutaneously (under the skin) four times biweekly
Experimental: MD 0.3 mg/kg
Subjects were injected biweekly four times with NNC0142-0002 at a dose of 0.3 mg/kg
Drug: NNC0142-0002
Multiple dose, ranging from 0.02 mg/kg up to max 4.0 mg/kg, administered subcutaneously (under the skin) four times biweekly
Experimental: MD 1.0 mg/kg
Subjects were injected biweekly four times with NNC0142-0002 at a dose of 1.0 mg/kg
Drug: NNC0142-0002
Multiple dose, ranging from 0.02 mg/kg up to max 4.0 mg/kg, administered subcutaneously (under the skin) four times biweekly
Experimental: MD 1.6 mg/kg
Subjects were injected biweekly four times with NNC0142-0002 at a dose of 1.6 mg/kg
Drug: NNC0142-0002
Multiple dose, ranging from 0.02 mg/kg up to max 4.0 mg/kg, administered subcutaneously (under the skin) four times biweekly
Experimental: MD 4.0 mg/kg
Subjects were injected biweekly four times with NNC0142-0002 at a dose of 4.0 mg/kg
Drug: NNC0142-0002
Multiple dose, ranging from 0.02 mg/kg up to max 4.0 mg/kg, administered subcutaneously (under the skin) four times biweekly
Experimental: MD Placebo
Subjects were injected biweekly four times with placebo
Drug: placebo
Single dose of 0 mg/kg administered subcutaneously (under the skin); cohort 1-7b on day 1, cohort 8-11 biweekly four times

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Active rheumatoid arthritis, characterized by a Disease Activity Score (DAS28) above 3.2, and a diagnosis of at least three months duration
  • Aged between 18 and 75 years (both inclusive)
  • Subjects on stable doses of methotrexate for at least 4 weeks prior to dosing
  • Use of highly effective contraception during the trial (both males and females)

Exclusion Criteria:

  • A chronic inflammatory autoimmune or joint disease other than RA (rheumatoid arthritis)
  • An active or latent tuberculosis
  • Any investigational or experimental therapy within 4 weeks or 5 half-lives (whichever is longer) prior to the screening visit
  • A known significant cardio-vascular disease
  • Vaccination against live virus or bacteria within 4 weeks prior to randomization
  • The use of concomitant medications that are prohibited in the trial (e.g., certain DMARDs (antirheumatic therapies that are disease modifying), biologics (here: biotechnologically produced antibodies), intra-articular corticoid-injections, etc.)
  • A positive test result for human immunodeficiency virus (HIV) infection, hepatitis B and/or hepatitis C, or tuberculosis skin test
  • Donation of greater than or equal to 400 ml of blood within 8 weeks prior to trial entry
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00927927

Locations
Germany
Berlin, Germany, 10117
Sponsors and Collaborators
Novo Nordisk A/S
Investigators
Study Director: Britta Væver Bysted, DVM, PhD Novo Nordisk A/S
  More Information

Additional Information:
No publications provided

Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT00927927     History of Changes
Other Study ID Numbers: NN8555-3618, 2008-008703-18
Study First Received: June 24, 2009
Results First Received: April 25, 2013
Last Updated: October 21, 2013
Health Authority: Germany: Paul-Ehrlich-Institut

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Inflammation
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on April 22, 2014