Clinical Trials Register

Summary
EudraCT Number:	2018-000930-37
Sponsor's Protocol Code Number:	M15-722
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2021-06-14
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2018-000930-37

A.3

Full title of the trial

A Multicenter, Single-Arm, Open-Label Study to Investigate the Efficacy and Safety of Ravagalimab (ABBV-323) in Subjects with Moderate to Severe Ulcerative Colitis Who Failed Prior Therapy

Studio multicentrico, in aperto e a braccio singolo per valutare l’efficacia e la sicurezza di Ravagalimab (ABBV-323) in soggetti con colite ulcerosa da moderata a severa che hanno fallito la precedente terapia

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A Study to Investigate safety and how well Ravagalimab (ABBV-323) works and how safe it is in Subjects with Moderate to Severe Ulcerative Colitis Who Failed Prior Therapy

Studio clinico per studiare la sicurezza e verificare l’azione di Ravagalimab (ABBV-323) e la sua sicurezza in soggetti affetti da colite ulcerosa di grado da moderato a grave per cui sia fallita una precedente terapia

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

M15-722

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	ABBVIE DEUTSCHLAND GMBH & CO. KG
B.1.3.4	Country	Germany
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	AbbVie INC
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	AbbVie Ltd
B.5.2	Functional name of contact point	EU clinical trials helpdesk
B.5.3	Address:
B.5.3.1	Street Address	AbbVie house, Vanwell business park
B.5.3.2	Town/ city	Maidenhead
B.5.3.3	Post code	SL6 4UB
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	00441628561090
B.5.5	Fax number	00441628461153
B.5.6	E-mail	eu-clinical-trials@abbvie.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Ravagalimab
D.3.2	Product code	[ABBV-323]
D.3.4	Pharmaceutical form	Powder for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	ABBV-323
D.3.9.4	EV Substance Code	SUB192927
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Ulcerative Colitis

Colite Ulcerosa

E.1.1.1

Medical condition in easily understood language

A long-term (chronic) condition where the colon and rectum (large intestine or large bowel) become inflamed.

Una condizione a lungo termine (cronica) in cui il colon e il retto (intestino crasso o intestino crasso) si infiammano.

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10045365
E.1.2	Term	Ulcerative colitis
E.1.2	System Organ Class	100000004856

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To characterize the efficacy, safety, and tolerability of Ravagalimab (ABBV-323) as induction treatment in subjects with moderately to severely active UC.

Esplorare l’efficacia, la sicurezza e la tollerabilità di Ravagalimab (ABBV-323) come terapia di induzione in soggetti con Colite Ulcerosa attiva da moderata a severa.

E.2.2

Secondary objectives of the trial

1. To assess pharmacokinetics (PK) and receptor occupancy (RO) of ABBV-323 in subjects with moderately to severely active UC.
2. To characterize the efficacy, safety, and tolerability of ABBV-323 as maintenance therapy in subjects with clinical response to ABBV-323 following induction therapy.

2. Valutare la farmacocinetica (PK) e l’occupazione del recettore (RO) di ABBV-323 in soggetti con Colite Ulcerosa attiva da moderata a severa.
3. Caratterizzare l’efficacia, la sicurezza e la tollerabilità di ABBV-323 come terapia di mantenimento in soggetti che rispondono a ABBV-323 a seguito della terapia di induzione.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

·Subjects must voluntarily sign and date an informed consent, approved by an independent ethics committee (IEC)/institutional review board (IRB), prior to the initiation of any screening or study-specific procedures.
·Adult male or female, between 18 and 75 years of age, inclusive, at time of the Baseline visit.
·Diagnosis of UC for at least 3 months prior to Baseline. Appropriate documentation of biopsy results consistent with the diagnosis of UC or in the assessment of the Investigator, must be available.
·Subject meets the following disease activity criteria: Active UC with an Adapted Mayo score of 5 to 9 points and endoscopic subscore of 2 to 3 (confirmed by central review).
·History of inadequate response, loss of response, or intolerance to one or more of the approved biologic therapies: infliximab, adalimumab, golimumab, vedolizumab, and/or tofacitinib (Note: If tofacitinib was received in a clinical trial, subject must have received open-label drug).
·Laboratory values that meet the following criteria:
- Serum aspartate transaminase (AST) and alanine transaminase (ALT) < o = 2 × upper limit of normal (ULN);Total white blood cell (WBC) count > o = 3.0 × 10^9 /L;
Confirmed COVID-19: the Baseline visit must be at least 14 days from onset of signs/symptoms or positive SARS-CoV-2 test; symptomatic subjects must have recovered, defined as resolution of fever without use of antipyretics and improvement in symptoms;
Suspected COVID-19: subjects with signs/symptoms suggestive of COVID-19, known exposure, or high risk behavior should undergo molecular (e.g., PCR) testing to rule out SARS-CoV-2 infection or must be asymptomatic for 14 days from a potential exposure.

• I soggetti devono firmare e datare volontariamente un consenso informato, approvato da un comitato etico indipendente, prima dell'inizio di qualsiasi procedura di screening o studio-specifica.
• Maschi o femmine adulti di età compresa tra i 18 ed i 75 anni compresi, al momento della visita di baseline.
• Diagnosi di CU di almeno 3 mesi prima della visita di Baseline. Deve essere disponibile un’ appropriata documentazione dei risultati della biopsia coerenti con la diagnosi di CU secondo il giudizio dello sperimentatore.
• Il soggetto soddisfa i seguenti criteri di attività della malattia: CU attiva con punteggio Mayo adattato da 5 a 9 punti e sottopungettio endoscopico da 2 a 3 (confermato da revisione centrale).
• Anamnesi di risposta inadeguata, perdita di risposta o intolleranza ad una o più terapie biologiche approvate: infliximab, adalimumab, golimumab, vedolizumab e/o tofacitinib (Nota: se il tofacitinib è stato ricevuto in una sperimentazione clinica, il soggetto deve aver ricevuto farmaco in aperto). I requisiti di dose e durata sono specificati nella Sezione 5.1.
• Valori di laboratorio che soddisfano i seguenti criteri:
- Siero aspartato transaminasi (AST) e alanina transaminasi (ALT) < o = 2 × limite superiore della norma (ULN); conteggio dei globuli bianchi totali (WBC) > o = 3,0 × 10^9 /L
COVID-19 confermato: la visita di baseline deve essere eseguita almento 14 giorni prima della comparsa di segni/sintomi o di tampone SARS-CoV-2 positivo; soggetti sintomatici devono essere andati incontro a guarigione, definita come la risoluzione della febbre senza uso di antipiretici e miglioramento dei sintomi;
COVID-19 sospetto: soggetti con segni/sintomi indicativi di COVID-19, esposizione a soggetto positivo o comportamento ad alto rischio devono essere sottoposti a tampone molecolare (es. PCR) per escludere una infezione da SARS-CoV-2 o devono essere asintomatici per 14 giorni dalla potenziale esposizione.

E.4

Principal exclusion criteria

- Subject must not have an active, chronic, or recurrent infection that based on the
Investigator's clinical assessment makes the subject an unsuitable candidate for the study
- Subject must not have any malignancy except for successfully treated non metastatic cutaneous
squamous cell or basal cell carcinoma or localized carcinoma in situ of the cervix.
- Subject must not have history of dysplasia of the gastrointestinal tract or evidence of dysplasia in any biopsy performed during the Screening endoscopy
- Confirmed COVID-19: the Baseline visit must be at least 14 days from onset of signs/symptoms or positive SARS-CoV-2 test; symptomatic subjects must have recovered, defined as resolution of fever without use of antipyretics and improvement in symptoms;
- Suspected COVID-19: subjects with signs/symptoms suggestive of COVID-19, known exposure, or high risk behavior should undergo molecular (e.g., PCR) testing to rule out SARS-CoV-2 infection or must be asymptomatic for 14 days from a potential exposure.

- Soggetto che non presenti alcuna infezione in fase attiva, cronica oppure ricorrente che in base al giudizio clinico dello sperimentatore renderebbe il soggetto non idoneo a partecipare allo studio clinico
- Soggetto che non presenti alcuna neoplasia maligna, ad eccezione del carcinoma cutaneo squamocellulare oppure basocellulare, oppure il carcinoma localizzato in situ della cervice uterina, trattati con successo e non metastatici
- Soggetto che non presenti storia di displasia del tratto gastrointestinale oppure evidenza di displasia rilevata da qualsiasi biopsia eseguita durante la procedura endoscopica allo Screening
- COVID-19 confermato: la visita di baseline deve essere eseguita almento 14 giorni prima della comparsa di segni/sintomi o di tampone SARS-CoV-2 positivo; i soggetti sintomatici devono essere andati incontro a guarigione, definita come la risoluzione della febbre senza uso di antipiretici e miglioramento dei sintomi;
- COVID-19 sospetto: soggetti con segni/sintomi indicativi di COVID-19, esposizione a soggetto positivo o comportamento ad alto rischio devono essere sottoposti a tampone molecolare (es. PCR) per escludere una infezione da SARS-CoV-2 o devono essere asintomatici per 14 giorni dalla potenziale esposizione.

E.5 End points

E.5.1

Primary end point(s)

The proportion of subjects with endoscopic improvement (Mayo endoscopic subscore of 0 or 1) at Week 8.

La proporzione di soggetti con miglioramento endoscopico (Sottopunteggio endoscopico Mayo di 0 o 1) alla settimana 8.

E.5.1.1

Timepoint(s) of evaluation of this end point

At week 8

Alla settimana 8

E.5.2

Secondary end point(s)

Secondary Endpoints (Weeks 0 to 12):
- Proportion of subjects with clinical remission per Adapted Mayo score at Week 8
- Proportion of subjects with clinical response per Adapted Mayo score at Week 8
- Proportion of subjects with clinical response per Partial Adapted Mayo score over time
- Proportion of subjects with clinical remission per Full Mayo score at Week 8 in subjects with a Full Mayo score of 6 to 12 at Baseline.
- Proportion of subjects with endoscopic remission at Week 8

Endpoint Secondari (dalla Settimana 0 alla Settimana 12):
- Percentuale di soggetti con remissione clinica in base al punteggio Adapted Mayo alla Settimana 8
- Percentuale di soggetti con risposta clinica in base al punteggio Adapted Mayo alla Settimana 8
- Percentuale di soggetti con risposta clinica in base al punteggio Partial Adapted Mayo nel tempo
- Percentuale di soggetti con remissione clinica in base al punteggio Full Mayo alla Settimana 8 in soggetti con punteggio Full Mayo al Baseline compreso fra 6 e 12.
- Percentuale di soggetti con remissione endoscopica alla Settimana 8

E.5.2.1

Timepoint(s) of evaluation of this end point

Time points provided in E.5.2

Tempo di rilevazione riportato in E.5.2

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Canada

Korea, Republic of

United States

France

Germany

Italy

Netherlands

Spain

United Kingdom

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

84 days after the last subject last dose of study drug

84 giorni dopo l'ultima dose dell'ultimo soggetto dell'ultimo farmaco di studio

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2019-04-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-11-26

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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