Clinical Trial Results:
Prospective, open-label, single-arm, single-center phase IV clinical trial to evaluate efficacy and safety of the adalimumab biosimilar Amgevita in subjects with moderate to severe active chronic inflammatory bowel diesease (Crohn's disease and ulcerative colitis)

Trial information Top of page
Trial identification
Sponsor protocol code	UKER-AMGEVITA-CED-NOVO-01
Additional study identifiers
ISRCTN number	-
US NCT number	-
WHO universal trial number (UTN)	-
Sponsors
Sponsor organisation name	Universitätsklinikum Erlangen
Sponsor organisation address	Maximiliansplatz 2, Erlangen, Germany, 91054
Public contact	Medizinische Klinik 1, Universitätsklinikum Erlangen, raja.atreya@uk-erlangen.de
Scientific contact	Medizinische Klinik 1, Universitätsklinikum Erlangen, raja.atreya@uk-erlangen.de
Paediatric regulatory details
Is trial part of an agreed paediatric investigation plan (PIP)	No
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Results analysis stage
Analysis stage	Final
Date of interim/final analysis	07 Mar 2022
Is this the analysis of the primary completion data?	Yes
Primary completion date	07 Mar 2022
Global end of trial reached?	Yes
Global end of trial date	07 Mar 2022
Was the trial ended prematurely?	Yes
General information about the trial
Main objective of the trial	To investigate efficacy of adalimumab biosimilar (Amgevita) in subjects with moderate to severe active chronic inflammatory bowel disease (Crohn's disease and ulcererative colitis)
Protection of trial subjects	To limit the risk of side effects, amgevita was used according to its SmPC, furthermore the patients on drug were closely monitored during trial participation.
Background therapy	-
Evidence for comparator	-
Actual start date of recruitment	16 Dec 2019
Long term follow-up planned	No
Independent data monitoring committee (IDMC) involvement?	No
Population of trial subjects
Number of subjects enrolled per country
Country: Number of subjects enrolled	Germany: 20
Worldwide total number of subjects	20
EEA total number of subjects	20
Number of subjects enrolled per age group
In utero	0
Preterm newborn - gestational age < 37 wk	0
Newborns (0-27 days)	0
Infants and toddlers (28 days-23 months)	0
Children (2-11 years)	0
Adolescents (12-17 years)	0
Adults (18-64 years)	20
From 65 to 84 years	0
85 years and over	0

Trial information Top of page

Subject disposition Top of page
Recruitment
Recruitment details	-
Pre-assignment
Screening details	male or female subjects, 18-80 years of age, diagnosis of chronic inflammatory bowel disease with indication for initial treatment with adalimumab in subjects with moderate to high grade disease activity and clinically insufficient response to or contraindication for systematic therapy with corticosteroids and/or immunosuppressants
Period 1
Period 1 title	Treatment period (overall period)
Is this the baseline period?	Yes
Allocation method	Not applicable
Blinding used	Not blinded
Blinding implementation details	no blinding
Arms
Arm title	All subjects
Arm description	All subjects who have received Amgevita at least once
Arm type	Experimental
Investigational medicinal product name	Amgevita
Investigational medicinal product code
Other name	biosimilar adalimumab
Pharmaceutical forms	Solution for injection in pre-filled pen, Solution for injection in pre-filled syringe
Routes of administration	Subcutaneous use
Dosage and administration details	induction: day 1: 160 mg s.c., day 15: 80 mg s.c. maintainance: 40 mg s.c. every 14 days (starting from day 29)
Number of subjects in period 1 All subjects Started 20 Completed 5 Not completed 15      Adverse event, non-fatal 1      early study termination 13      Lack of efficacy 1

Subject disposition Top of page

Baseline characteristics Top of page
Baseline characteristics reporting groups
Reporting group title	Treatment period
Reporting group description	-
Reporting group values Treatment period Total Number of subjects 20 20 Age categorical Units: Subjects     In utero 0 0     Preterm newborn infants (gestational age < 37 wks) 0 0     Newborns (0-27 days) 0 0     Infants and toddlers (28 days-23 months) 0 0     Children (2-11 years) 0 0     Adolescents (12-17 years) 0 0     Adults (18-64 years) 20 20     From 65-84 years 0 0     85 years and over 0 0 Gender categorical Units: Subjects     Female 11 11     Male 9 9

Baseline characteristics Top of page

End points Top of page
End points reporting groups
Reporting group title	All subjects
Reporting group description	All subjects who have received Amgevita at least once

End points Top of page

Primary: Clinical response to Amgevita in patients with moderate to severe CED Top of page
End point title	Clinical response to Amgevita in patients with moderate to severe CED [1]
End point description
End point type	Primary
End point timeframe	at week 13 after onset of therapy
Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: no statistical analyses due to small number of study participants (early termination after enrollment of 20 [planned 87] subjects due to poor recruitment)
End point values All subjects Number of subjects analysed 20 Units: subject     Responder 18     Non-Responder 2
No statistical analyses for this end point

Primary: Clinical response to Amgevita in patients with moderate to severe CED Top of page

Adverse events Top of page
Adverse events information
Timeframe for reporting adverse events	from Day 1 (visit 2) until week 52 (visit 7, EoS)
Assessment type	Systematic
Dictionary used for adverse event reporting
Dictionary name	MedDRA
Dictionary version	27
Reporting groups
Reporting group title	Safety Analysis Set
Reporting group description	all subjects who have received the IMP at least once
Serious adverse events Safety Analysis Set Total subjects affected by serious adverse events      subjects affected / exposed 1 / 20 (5.00%)      number of deaths (all causes) 0      number of deaths resulting from adverse events 0 Gastrointestinal disorders Ileus      subjects affected / exposed 1 / 20 (5.00%)      occurrences causally related to treatment / all 0 / 2      deaths causally related to treatment / all 0 / 0
Frequency threshold for reporting non-serious adverse events: 1%
Non-serious adverse events Safety Analysis Set Total subjects affected by non serious adverse events      subjects affected / exposed 16 / 20 (80.00%) Vascular disorders Hypertension      subjects affected / exposed 1 / 20 (5.00%)      occurrences all number 1 General disorders and administration site conditions Application site reaction      subjects affected / exposed 1 / 20 (5.00%)      occurrences all number 1 Fatigue      subjects affected / exposed 1 / 20 (5.00%)      occurrences all number 1 Influenza like illness      subjects affected / exposed 2 / 20 (10.00%)      occurrences all number 2 Respiratory, thoracic and mediastinal disorders Cough      subjects affected / exposed 2 / 20 (10.00%)      occurrences all number 2 Rhinorrhoea      subjects affected / exposed 1 / 20 (5.00%)      occurrences all number 1 Psychiatric disorders Insomnia      subjects affected / exposed 1 / 20 (5.00%)      occurrences all number 1 Investigations C-reactive protein increased      subjects affected / exposed 2 / 20 (10.00%)      occurrences all number 2 Faecal calprotectin increased      subjects affected / exposed 3 / 20 (15.00%)      occurrences all number 4 Injury, poisoning and procedural complications Anastomotic ulcer      subjects affected / exposed 1 / 20 (5.00%)      occurrences all number 1 Rib fracture      subjects affected / exposed 1 / 20 (5.00%)      occurrences all number 1 Skin laceration      subjects affected / exposed 1 / 20 (5.00%)      occurrences all number 1 Nervous system disorders Headache      subjects affected / exposed 1 / 20 (5.00%)      occurrences all number 2 Intercostal neuralgia      subjects affected / exposed 1 / 20 (5.00%)      occurrences all number 2 Migraine      subjects affected / exposed 1 / 20 (5.00%)      occurrences all number 1 Paraesthesia      subjects affected / exposed 1 / 20 (5.00%)      occurrences all number 1 Sciatica      subjects affected / exposed 1 / 20 (5.00%)      occurrences all number 1 Blood and lymphatic system disorders Lymphadenitis      subjects affected / exposed 1 / 20 (5.00%)      occurrences all number 1 Ear and labyrinth disorders Vertigo      subjects affected / exposed 1 / 20 (5.00%)      occurrences all number 2 Gastrointestinal disorders Abdominal pain      subjects affected / exposed 1 / 20 (5.00%)      occurrences all number 1 Crohn's disease      subjects affected / exposed 1 / 20 (5.00%)      occurrences all number 1 Diarrhoea      subjects affected / exposed 1 / 20 (5.00%)      occurrences all number 1 Dysphagia      subjects affected / exposed 1 / 20 (5.00%)      occurrences all number 1 Nausea      subjects affected / exposed 1 / 20 (5.00%)      occurrences all number 1 Vomiting      subjects affected / exposed 1 / 20 (5.00%)      occurrences all number 1 Skin and subcutaneous tissue disorders Alopecia      subjects affected / exposed 1 / 20 (5.00%)      occurrences all number 1 Cutaneous symptom      subjects affected / exposed 1 / 20 (5.00%)      occurrences all number 1 Drug eruption      subjects affected / exposed 1 / 20 (5.00%)      occurrences all number 1 Eczema      subjects affected / exposed 1 / 20 (5.00%)      occurrences all number 1 Musculoskeletal and connective tissue disorders Arthralgia      subjects affected / exposed 2 / 20 (10.00%)      occurrences all number 2 Pain in extremity      subjects affected / exposed 1 / 20 (5.00%)      occurrences all number 1 Infections and infestations COVID-19      subjects affected / exposed 2 / 20 (10.00%)      occurrences all number 2 Cystitis      subjects affected / exposed 1 / 20 (5.00%)      occurrences all number 1 Gastroenteritis      subjects affected / exposed 1 / 20 (5.00%)      occurrences all number 1 Nasopharyngitis      subjects affected / exposed 2 / 20 (10.00%)      occurrences all number 2 Oral herpes      subjects affected / exposed 1 / 20 (5.00%)      occurrences all number 1 Tonsillitis      subjects affected / exposed 1 / 20 (5.00%)      occurrences all number 1 Vaginal infection      subjects affected / exposed 1 / 20 (5.00%)      occurrences all number 1

Adverse events Top of page

More information Top of page
Substantial protocol amendments (globally)
Were there any global substantial amendments to the protocol? Yes
Date	Amendment
11 May 2021	A01-SAM-CSP-AMGEVITA: IC: endoscopic diagnostic also accepted if more than 6 (up to 12) weeks prior to screening
Interruptions (globally)
Were there any global interruptions to the trial? No
Limitations and caveats
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
Early termination due to poor recruitment after 20 (instead of 87) subjects

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