Efficacy of NNC0142-0002 in Subjects With Rheumatoid Arthritis (RA)

• Sponsor: Janssen Research & Development, LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01181050
• Collaborator: (none)
• Enrollment: 63
• Locations: 3
• Arms: 2
• Duration (Months): 20
• Patients Per Site: 21
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

This trial is conducted in Europe. The aim of this trial is to evaluate the clinical efficacy of a single dose of NNC0142-0002 administered to subjects with active rheumatoid arthritis (RA).

Condition or Disease	Intervention/Treatment	Phase
Inflammation; Rheumatoid Arthritis	Drug: NNC0142-0002; Drug: placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 63 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomised, Single-dose, Double-blind, Placebo-controlled, Parallel-group Trial to Assess Clinical Efficacy of NNC0142-0002 in Subjects With Active Rheumatoid Arthritis
• Study Start Date: Aug 1, 2010
• Actual Primary Completion Date: Apr 1, 2012
• Actual Study Completion Date: Apr 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 4.0 mg/kg Subjects received a single dose of 4 mg/kg NNC0142-0002	Drug: NNC0142-0002; A single dose of 4 mg NNC 0142-0000-0002/kg bodyweight. Administered subcutaneously (s.c., under the skin).
Placebo Comparator: Placebo Subjects received a single dose of placebo	Drug: placebo; A single dose of 4 mg NNC 0142-0000-0002 placebo/kg bodyweight. Administered subcutaneously (s.c., under the skin).

Outcome Measures

Primary Outcome Measures

1. Change in DAS28-CRP After 12 Weeks of Treatment [Week 0, Week 12]

   DAS28-CRP=0.56×sqrt(tender joints [count:1-28])+0.28×sqrt(swollen joints [count:1-28])+0.36×Ln(CRP level+1)+0.014×(patient's disease assessment on 0-100 mm scale [100=most severe])+0.96. Range: 0.96 to no upper limit. Higher score=more severe disease. Mean change in DAS-CRP score after 12 Weeks of treatment.

Secondary Outcome Measures

1. Change in DAS28-CRP After 6 Weeks of Treatment. [Week 0, Week 6]

   DAS28-CRP=0.56×sqrt(tender joints [count:1-28])+0.28×sqrt(swollen joints [count:1-28])+0.36×Ln(CRP level+1)+0.014×(patient's disease assessment on 0-100 mm scale [100=most severe])+0.96. Range: 0.96 to no upper limit. Higher score=more severe disease. Mean change in DAS-CRP score after 6 Weeks of treatment.

2. Change in DAS28-CRP After 24 Weeks of Treatment. [Week 0, Week 24]

   DAS28-CRP=0.56×sqrt(tender joints [count:1-28])+0.28×sqrt(swollen joints [count:1-28])+0.36×Ln(CRP level+1)+0.014×(patient's disease assessment on 0-100 mm scale [100=most severe])+0.96. Range: 0.96 to no upper limit. Higher score=more severe disease. Mean change in DAS-CRP score after 24 Weeks of treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• A diagnosis of RA meeting the American College of Rheumatology 1987 (ACR1987) criteria, obtained at least three months prior to dosing with the trial product

• Subjects with active RA having a Disease Activity Score (DAS28-CRP) of 4.5 or more, at least five tender and five swollen joints (can be the same), including one swollen wrist or at least two swollen ipsilateral metacarpophalangeal (MCP) joints (second to fifth)

• Concomitant treatment with methotrexate (MTX) (7.5-25 mg/week) for at least 12 weeks, with stable dose for at least 4 weeks prior to dosing

• Ability to be examined by Magnetic Resonance Imaging (MRI)

• Having failed no biologic therapies for RA and no more than two non-biologic disease modifying antirheumatic drugs

Exclusion Criteria:

• Chronic inflammatory autoimmune disease other than RA (rheumatoid arthritis)

• Any ongoing chronic or active infectious disease or microbial infection requiring systemic oral or intravenous treatment against infection within 1 month prior to trial start

• Body mass index (BMI) below or equal to 18 or above or equal to 40 kg/m^2

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Berlin		Germany	13353
2		Moscow		Russian Federation	109240
3		Kiev		Ukraine	03680

Sponsors and Collaborators

• Janssen Research & Development, LLC

Investigators

• Study Director: Global Clinical Registry (GCR, 1452), Novo Nordisk A/S

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Clinical Trials at Novo Nordisk

Publications

None provided.

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT01181050
• Other Study ID Numbers: NN8555-3796; U1111-1114-9194; 2010-019261-28
• First Posted: Aug 13, 2010
• Last Update Posted: Oct 3, 2016
• Last Verified: Aug 1, 2016

• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Inflammation

Study Results

Participant Flow

Recruitment Details	The trial was conducted at 8 trial sites in 3 different countries (Germany, the Russian Federation and Ukraine) as follows: Germany: 1 site, the Russian Federation: 6 sites and Ukraine: 1 site. All sites enrolled, randomised and dosed at least 1 subject.

Arm/Group Title	4.0 mg/kg	Placebo
Arm/Group Description	Subjects received a single dose of 4 mg/kg NNC0142-0002	Subjects received a single dose of placebo
Period Title: Overall Study
STARTED	41	22
COMPLETED	41	22
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	4.0 mg/kg	Placebo	Total
Arm/Group Description	Subjects received a single dose of 4 mg/kg NNC0142-0002	Subjects received a single dose of placebo	Total of all reporting groups
Overall Participants	41	22	63
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52.6 (10.8)	52.0 (10.8)	52.4 (10.7)
Sex: Female, Male (Count of Participants)
Female	38 92.7%	19 86.4%	57 90.5%
Male	3 7.3%	3 13.6%	6 9.5%
DAS28-CRP (Disease Activity Score based on count of 28 joints and the C-reactive protein) (scores) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [scores]	5.4 (0.9)	5.4 (1.0)	5.4 (0.9)

Outcome Measures

1. Primary Outcome

Title	Change in DAS28-CRP After 12 Weeks of Treatment
Description	DAS28-CRP=0.56×sqrt(tender joints [count:1-28])+0.28×sqrt(swollen joints [count:1-28])+0.36×Ln(CRP level+1)+0.014×(patient's disease assessment on 0-100 mm scale [100=most severe])+0.96. Range: 0.96 to no upper limit. Higher score=more severe disease. Mean change in DAS-CRP score after 12 Weeks of treatment.
Time Frame	Week 0, Week 12

Outcome Measure Data

Analysis Population Description

Change in DAS28-CRP was calculated by using last observation carried forward method.

Arm/Group Title	4.0 mg/kg	Placebo
Arm/Group Description	Subjects received a single dose of 4 mg/kg NNC0142-0002	Subjects received a single dose of placebo
Measure Participants	41	22
Mean (Standard Deviation) [scores]	-1.0 (1.0)	-1.0 (1.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	4.0 mg/kg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9334
	Comments
	Method	Mixed effect model repeated measures
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-0.02
	Confidence Interval	() 95%; -0.54 to 0.50
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change in DAS28-CRP After 6 Weeks of Treatment.
Description	DAS28-CRP=0.56×sqrt(tender joints [count:1-28])+0.28×sqrt(swollen joints [count:1-28])+0.36×Ln(CRP level+1)+0.014×(patient's disease assessment on 0-100 mm scale [100=most severe])+0.96. Range: 0.96 to no upper limit. Higher score=more severe disease. Mean change in DAS-CRP score after 6 Weeks of treatment.
Time Frame	Week 0, Week 6

Outcome Measure Data

Analysis Population Description

Change in DAS28-CRP was calculated by using last observation carried forward method.

Arm/Group Title	4.0 mg/kg	Placebo
Arm/Group Description	Subjects received a single dose of 4 mg/kg NNC0142-0002	Subjects received a single dose of placebo
Measure Participants	41	22
Mean (Standard Deviation) [scores]	-0.9 (1.1)	-1.0 (0.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	4.0 mg/kg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8293
	Comments
	Method	Mixed effect model repeated measures
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	0.06
	Confidence Interval	() 95%; -0.46 to 0.58
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change in DAS28-CRP After 24 Weeks of Treatment.
Description	DAS28-CRP=0.56×sqrt(tender joints [count:1-28])+0.28×sqrt(swollen joints [count:1-28])+0.36×Ln(CRP level+1)+0.014×(patient's disease assessment on 0-100 mm scale [100=most severe])+0.96. Range: 0.96 to no upper limit. Higher score=more severe disease. Mean change in DAS-CRP score after 24 Weeks of treatment.
Time Frame	Week 0, Week 24

Outcome Measure Data

Analysis Population Description

Change in DAS28-CRP was calculated by using last observation carried forward method.

Arm/Group Title	4.0 mg/kg	Placebo
Arm/Group Description	Subjects received a single dose of 4 mg/kg NNC0142-0002	Subjects received a single dose of placebo
Measure Participants	41	22
Mean (Standard Deviation) [scores]	-1.3 (1.1)	-1.3 (1.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	4.0 mg/kg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8867
	Comments
	Method	Mixed effect model repeated measures
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-0.04
	Confidence Interval	() 95%; -0.65 to 0.56
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	The adverse events were collected from dosing until end of trial (a total of 24 weeks)
Adverse Event Reporting Description	Safety analysis set includes all subjects who received one dose of the investigational product or its comparator
Arm/Group Title	4.0 mg/kg		Placebo
Arm/Group Description	Subjects received a single dose of 4 mg/kg NNC0142-0002		Subjects received a single dose of placebo
All Cause Mortality
	4.0 mg/kg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	4.0 mg/kg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/41 (7.3%)		1/22 (4.5%)
Gastrointestinal disorders
Gastritis erosive	1/41 (2.4%)	1	0/22 (0%)	0
Pancreatitis chronic	1/41 (2.4%)	1	0/22 (0%)	0
Hepatobiliary disorders
Portal hypertension	0/41 (0%)	0	1/22 (4.5%)	1
Musculoskeletal and connective tissue disorders
Musculoskeletal pain	1/41 (2.4%)	1	0/22 (0%)	0
Rheumatoid arthritis	1/41 (2.4%)	1	0/22 (0%)	0
Other (Not Including Serious) Adverse Events
	4.0 mg/kg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/41 (12.2%)		5/22 (22.7%)
Infections and infestations
Respiratory tract infection viral	1/41 (2.4%)	2	2/22 (9.1%)	2
Investigations
Alanine aminotransferase increased	0/41 (0%)	0	2/22 (9.1%)	3
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis	4/41 (9.8%)	4	1/22 (4.5%)	1

Limitations/Caveats

As per protocol, this clinical proof-of-principle trial investigated a limited number of participants and doses (single-dose regimen).

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Novo Nordisk reserves the right to defer data release until specified milestones, e.g. availability of a clinical trial report. Novo Nordisk reserves the right to postpone publication and/or communication for less than 60 days to protect intellectual property. Novo Nordisk reserves the right to prior review of site-specific publications and to ask for deferment of publication of individual site results until after the primary manuscript is accepted for publication.