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Clinical Trial Results:
Comparison of the effect of treatment with NSAIDs added to anti-TNF therapy versus anti-TNF therapy alone on progression of structural damage in the spine over two years in patients with ankylosing spondylitis: a randomized controlled multicentre trial (CONSUL)

Summary
EudraCT number	2016-000615-33
Trial protocol	DE
Global end of trial date	25 Feb 2021

Results information
Results version number	v1(current)
This version publication date	31 Jul 2022
First version publication date	31 Jul 2022
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

CONSUL2016

ISRCTN number

US NCT number

NCT02758782

WHO universal trial number (UTN)

Sponsor organisation name

Charité Universitätsmedizin Berlin

Sponsor organisation address

Charitéplatz 1, Berlin, Germany, 10117

Public contact

Rheumatology at Campus B Franklin, Charite Universitaetsmedizin, +49 3084454144, denis.poddubnyy@charite.de

Scientific contact

Rheumatology at Campus B Franklin, Charite Universitaetsmedizin, +49 3084454144, denis.poddubnyy@charite.de

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

25 Feb 2021

Is this the analysis of the primary completion data?

Yes

Primary completion date

25 Feb 2021

Global end of trial reached?

Yes

Global end of trial date

25 Feb 2021

Was the trial ended prematurely?

Main objective of the trial

To evaluate the impact of treatment with a non-steroidal anti-inflammatory drug (NSAID) – Celecoxib – when added to anti-tumour necrosis factor (TNF) therapy – Golimumab – as compared to anti-TNF therapy (Golimumab) alone on progression of structural damage in the spine over two years in patients with AS (Absolute progression of the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) over two years of therapy (weeks 12-108) in the Phase II (core phase) of the trial)

Protection of trial subjects

The study was conducted according to the ethical principles of the Declaration of Helsinki (JAMA. 2013;310(20):2191-2194). The study protocol and all amendments were reviewed by the Independent Ethics Commission of the State of Berlin (Ethik-Kommission des Landes Berlin) and Independent Ethics Committees for each center. All patients provided a written informed consent prior to randomization. The International Conference of Harmonisation Good Clinical Practice guidelines and the German drug law (Arzneimittelgesetz).

Background therapy

Evidence for comparator

Actual start date of recruitment

20 Jun 2016

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Germany: 128

Worldwide total number of subjects

128

EEA total number of subjects

128

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

128

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Start of recruitment was on September 19th 2016 and was finished on December 12th in 2018. Recruitment was conducted at 16 study centres in Germany.

Screening details

157 patients were screened 6 week prior run-in phase( treatment with Golimumab); 130 fulfilled the inclusion and exclusion criteria. 2 patients withdrew their informed consent remaining n=128 patients were enrolled into the run-in phase. Run-in phase was 12 weeks. 19 Patientes were non responders and were excluded.

Number of subjects started

128

Number of subjects completed

109

Reason: Number of subjects

non responders: 19

Period 1 title

core phase (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Golimumab & celecoxib

Arm description

Arm type

Experimental

Investigational medicinal product name

Golimumab

Investigational medicinal product code

Other name

Simponi

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Golimumab 50mg s.c. per Month

Investigational medicinal product name

Celebrex

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

a daily dose of 400 mg/day

Golimumab alone

Arm description

Arm type

Active comparator

Investigational medicinal product name

Golimumab

Investigational medicinal product code

Other name

Simponi

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

golimumab 50 mg subcutaneously every 4 weeks alone

Number of subjects in period 1 ^[1]	Golimumab & celecoxib	Golimumab alone
Started	54	55
Completed	45	52
Not completed	9	3
Adverse event, non-fatal	4	1
Lack of efficacy	2	1
Protocol deviation	3	1

Notes
[1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: 109 patients fulfilled the BASDAI response criterion at week 12 and were randomized with 54 patients in the combination arm with Golimumab + Celecoxib and 55 patients in the monotherapy with Golimumab arm.

Baseline characteristics

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Reporting group title

Golimumab & celecoxib

Reporting group description

Reporting group title

Golimumab alone

Reporting group description

Reporting group values	Golimumab & celecoxib	Golimumab alone	Total
Number of subjects	54	55	109
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (full range (min-max))	39.9 (21 to 59)	37.5 (19 to 63)	-
Gender categorical
Units: Subjects
Female	14	14	28
Male	40	41	81

End points

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Reporting group title

Golimumab & celecoxib

Reporting group description

Reporting group title

Golimumab alone

Reporting group description

Primary: mSASSS progression and mSASSS at year 2

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End point title

mSASSS progression and mSASSS at year 2

End point description

The percentage of patients with radiographic progression (mSASSS >=2) was only slightly higher in the golimumab alone group (27.2% vs 23.6%) (Similar in the case of (mSASSS > 0: 59.7% vs. 56.3%).

End point type

Primary

End point timeframe

108 weeks

End point values	Golimumab & celecoxib	Golimumab alone
Number of subjects analysed	54	55
Units: Score
arithmetic mean (standard deviation)
mSASSS change	1.1 ( 3 )	1.7 ( 3.5 )
mSASSS year 2	12.9 ( 17.9 )	12.4 ( 14.5 )

The radiographic progression

Comparison groups

Golimumab alone v Golimumab & celecoxib

Number of subjects included in analysis

109

Analysis specification

Pre-specified

Analysis type

superiority

P-value

≤ 0.05 ^[1]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[1] - The difference in mSASSS progression did not achieve statistical significance (p=0.79, Mann-Whitney U-test).

Secondary: Change Bath Ankylosing Spondylitis

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End point title

Change Bath Ankylosing Spondylitis

End point description

End point type

Secondary

End point timeframe

108 weeks

End point values	Golimumab & celecoxib	Golimumab alone
Number of subjects analysed	45	52
Units: Score
arithmetic mean (standard deviation)
BASDAI	6.2 ( 1 )	6.2 ( 1.2 )
BASFI	5.6 ( 1.4 )	4.6 ( 1.8 )

No statistical analyses for this end point

Secondary: CRP

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End point title

CRP

End point description

End point type

Secondary

End point timeframe

108 weeks

End point values	Golimumab & celecoxib	Golimumab alone
Number of subjects analysed	45	52
Units: milligram(s)/cubic metre
arithmetic mean (full range (min-max))	9.1 (0.4 to 115.5)	9.1 (0.5 to 146.7)

No statistical analyses for this end point

Secondary: New syndesmophytes, growth of syndesmophytes

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End point title

New syndesmophytes, growth of syndesmophytes

End point description

patients with development of new syndesmophytes and of growth of syndesmophytes and combination of both scored by >= 2 readers or three readers

End point type

Secondary

End point timeframe

108 Weeks

End point values	Golimumab & celecoxib	Golimumab alone
Number of subjects analysed	45	52
Units: Subjects
New syndesm. >=2reader	13	17
New syndesm. 3 reader	5	13
Growth of synd. >=2reader	4	8
Growth of synd. 3 reader	1	4
New/ growth of synd. >=2reader	15	18
New/ growth of synd. 3 reader	5	14

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

108 weeks

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

21.1

Reporting group title

golimumab + celecoxib

Reporting group description

Reporting group title

golimumab alone

Reporting group description

Serious adverse events	golimumab + celecoxib	golimumab alone
Total subjects affected by serious adverse events
subjects affected / exposed	7 / 54 (12.96%)	5 / 55 (9.09%)
number of deaths (all causes)	0	0
number of deaths resulting from adverse events	0	0
Injury, poisoning and procedural complications
Electric injury
subjects affected / exposed	1 / 54 (1.85%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Surgical and medical procedures
Meniscus operation
subjects affected / exposed	1 / 54 (1.85%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nervous system disorders
Chronic focal encephalitis
subjects affected / exposed	1 / 54 (1.85%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Facial nerve paresis
subjects affected / exposed	1 / 54 (1.85%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
subjects affected / exposed	0 / 54 (0.00%)	1 / 55 (1.82%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Psychiatric disorders
Depression
subjects affected / exposed	1 / 54 (1.85%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Meniscopathy
subjects affected / exposed	0 / 54 (0.00%)	1 / 55 (1.82%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Erysipelas
subjects affected / exposed	1 / 54 (1.85%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	0 / 54 (0.00%)	1 / 55 (1.82%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Tendon infection
subjects affected / exposed	0 / 54 (0.00%)	1 / 55 (1.82%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Acute gastroenteritis
subjects affected / exposed	0 / 54 (0.00%)	1 / 55 (1.82%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 1.5%

Non-serious adverse events	golimumab + celecoxib	golimumab alone
Total subjects affected by non serious adverse events
subjects affected / exposed	51 / 54 (94.44%)	48 / 55 (87.27%)
Investigations
Transaminases increased
subjects affected / exposed	10 / 54 (18.52%)	9 / 55 (16.36%)
occurrences all number	11	12
Injury, poisoning and procedural complications
Injection site reaction
subjects affected / exposed	1 / 54 (1.85%)	1 / 55 (1.82%)
occurrences all number	7	1
Vascular disorders
Arterial hypertension
subjects affected / exposed	7 / 54 (12.96%)	5 / 55 (9.09%)
occurrences all number	8	7
Nervous system disorders
Headache
subjects affected / exposed	5 / 54 (9.26%)	7 / 55 (12.73%)
occurrences all number	6	7
Immune system disorders
Axial spondyloarthritis
subjects affected / exposed	5 / 54 (9.26%)	4 / 55 (7.27%)
occurrences all number	5	5
Eye disorders
Conjunctivitis
subjects affected / exposed	1 / 54 (1.85%)	5 / 55 (9.09%)
occurrences all number	1	6
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	4 / 54 (7.41%)	5 / 55 (9.09%)
occurrences all number	5	5
Diarrhoea
subjects affected / exposed	6 / 54 (11.11%)	4 / 55 (7.27%)
occurrences all number	7	4
Gastroenteritis
subjects affected / exposed	5 / 54 (9.26%)	7 / 55 (12.73%)
occurrences all number	7	7
Skin and subcutaneous tissue disorders
Atopic eczema
subjects affected / exposed	3 / 54 (5.56%)	0 / 55 (0.00%)
occurrences all number	8	0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	1 / 54 (1.85%)	5 / 55 (9.09%)
occurrences all number	1	6
Joint pain
subjects affected / exposed	0 / 54 (0.00%)	6 / 55 (10.91%)
occurrences all number	0	7
Infections and infestations
Herpes labialis
subjects affected / exposed	3 / 54 (5.56%)	5 / 55 (9.09%)
occurrences all number	11	6
Pharyngitis
subjects affected / exposed	5 / 54 (9.26%)	0 / 55 (0.00%)
occurrences all number	8	0
Rhinitis
subjects affected / exposed	5 / 54 (9.26%)	6 / 55 (10.91%)
occurrences all number	8	8
Sinusitis
subjects affected / exposed	6 / 54 (11.11%)	7 / 55 (12.73%)
occurrences all number	8	8
Tonsillitis
subjects affected / exposed	5 / 54 (9.26%)	1 / 55 (1.82%)
occurrences all number	7	2
Urinary tract infection
subjects affected / exposed	2 / 54 (3.70%)	3 / 55 (5.45%)
occurrences all number	8	6
Acute upper respiratory tract infection
subjects affected / exposed	35 / 54 (64.81%)	38 / 55 (69.09%)
occurrences all number	73	92
Bronchitis
subjects affected / exposed	8 / 54 (14.81%)	4 / 55 (7.27%)
occurrences all number	10	4

More information

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Were there any global substantial amendments to the protocol? Yes

07 Mar 2017

Protocol clarifications concerning inclusion and exclusion criteria, safety assessment and specification of study related procedures

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

http://www.ncbi.nlm.nih.gov/pubmed/28601821

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Clinical trials

Clinical Trial Results:
Comparison of the effect of treatment with NSAIDs added to anti-TNF therapy versus anti-TNF therapy alone on progression of structural damage in the spine over two years in patients with ankylosing spondylitis: a randomized controlled multicentre trial (CONSUL)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: mSASSS progression and mSASSS at year 2

Primary: mSASSS progression and mSASSS at year 2

Secondary: Change Bath Ankylosing Spondylitis

Secondary: Change Bath Ankylosing Spondylitis

Secondary: CRP

Secondary: CRP

Secondary: New syndesmophytes, growth of syndesmophytes

Secondary: New syndesmophytes, growth of syndesmophytes

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

Online references

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Clinical trials

Clinical Trial Results: Comparison of the effect of treatment with NSAIDs added to anti-TNF therapy versus anti-TNF therapy alone on progression of structural damage in the spine over two years in patients with ankylosing spondylitis: a randomized controlled multicentre trial (CONSUL)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: mSASSS progression and mSASSS at year 2

Primary: mSASSS progression and mSASSS at year 2

Secondary: Change Bath Ankylosing Spondylitis

Secondary: Change Bath Ankylosing Spondylitis

Secondary: CRP

Secondary: CRP

Secondary: New syndesmophytes, growth of syndesmophytes

Secondary: New syndesmophytes, growth of syndesmophytes

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

Online references

More information

Clinical Trial Results:
Comparison of the effect of treatment with NSAIDs added to anti-TNF therapy versus anti-TNF therapy alone on progression of structural damage in the spine over two years in patients with ankylosing spondylitis: a randomized controlled multicentre trial (CONSUL)