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

• ClinicalTrials.gov Identifier: NCT00927927
• Recruitment Status: Completed
• First Posted: June 25, 2009
• Results First Posted: October 21, 2013
• Last Update Posted: October 3, 2016
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Inflammation; Rheumatoid Arthritis	Drug: NNC0142-0002; Drug: placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 65 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Double (Participant, 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
• Study Start Date: June 2009
• Actual Primary Completion Date: December 2011
• Actual Study Completion Date: December 2011

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. 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. ]
   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 :

1. 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. ]
   Systemic exposure to NNC0142-0002.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

Locations

Germany

Berlin, Germany, 10117

Sponsors and Collaborators

Janssen Research & Development, LLC

Investigators

• Study Director: Britta Væver Bysted, DVM, PhD; Novo Nordisk A/S

More Information

Additional Information:

Clinical Trials at Novo Nordisk 

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT00927927
• Other Study ID Numbers: NN8555-3618; 2008-008703-18 ( EudraCT Number )
• First Posted: June 25, 2009
• Results First Posted: October 21, 2013
• Last Update Posted: October 3, 2016
• Last Verified: August 2016

Additional relevant MeSH terms:

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