Clinical Trials Register

Summary
EudraCT Number:	2017-000937-30
Sponsor's Protocol Code Number:	ABX464-101
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2017-09-19
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

France - ANSM

A.2

EudraCT number

2017-000937-30

A.3

Full title of the trial

A Phase IIa study to evaluate the safety and efficacy of ABX464 50 mg once daily versus Placebo in subjects with Moderate to Severe Active Ulcerative Colitis who have failed or are intolerant to immunomodulators, Anti-TNFα, vedolizumab and/or corticosteroids.

Etude de phase IIa comparant la tolérance et l’efficacité d’ABX464 administré à la dose quotidienne de 50 mg à un placebo chez des sujets présentant une rectocolite hémorragique active modérée à sévère résistants ou intolérants aux traitements immunomodulateurs, aux Anti-TNFα, au vedolizumab et/ou aux corticoïdes.

A.3.1

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

Investigate the efficacy and safety of study drug ABX464 50 mg once daily versus placebo with patients with moderate to severe Active Ulcerative Colitis.

Evaluer la tolérance et l’efficacité de l’ABX464 50 mg une fois par jour par rapport au placebo chez des patients atteints de colite ulcéreuse active modérée à sévère.

A.3.2

Name or abbreviated title of the trial where available

Safety and efficacy study of ABX464 in patients with moderate to severe Active Ulcerative Colitis.

Etude de tolérance et d’efficacité de l’ABX464 chez des patients atteints de colite ulcéreuse active

A.4.1

Sponsor's protocol code number

ABX464-101

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	ABIVAX
B.1.3.4	Country	France
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	Abivax
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Abivax
B.5.2	Functional name of contact point	Head of Clinical Operations
B.5.3	Address:
B.5.3.1	Street Address	5 Rue dela Baume
B.5.3.2	Town/ city	Paris
B.5.3.3	Post code	75008
B.5.3.4	Country	France
B.5.4	Telephone number	+33 153830961
B.5.6	E-mail	paul.gineste@abivax.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.3.2	Product code	ABX464
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ABX464
D.3.9.2	Current sponsor code	ABX464
D.3.9.3	Other descriptive name	ABX464
D.3.9.4	EV Substance Code	SUB184487
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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	No
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule, hard
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Moderate to severe Ulcerative Colitis.

Colite ulcéreuse modérée à sévère.

E.1.1.1

Medical condition in easily understood language

In Ulcerative Colitis the lining of the colon becomes inflamed and develops tiny open sores that produce pus and mucous.This causes abdominal discomfort and frequent emptying of the colon (diarrhoea).

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	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10066678
E.1.2	Term	Acute ulcerative colitis
E.1.2	System Organ Class	100000016670

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of the study is to evaluate safety of ABX464 given at 50 mg once daily versus Placebo in subjects with Moderate to Severe Active Ulcerative Colitis who have failed or are intolerant to immunomodulators, Anti-TNFα, vedolizumab and/or corticosteroids.

E.2.2

Secondary objectives of the trial

To evaluate the effect of ABX464 :
-on the expression of IL-22 in serum and rectal/sigmoidal tissue compared to placebo in subjects with Moderate to Severe Active Ulcerative Colitis.
-on miR-124 expression in whole blood (PAXgene®) and in tissue (RNA later) vs placebo in subjects with Moderate to Severe Active Ulcerative Colitis.
-on the rectal/sigmoidal infiltrates (Geboes score) vs placebo in subjects with Moderate to Severe Active Ulcerative Colitis.
-on the rectal microbiome compared to placebo in subjects with Moderate to Severe Active Ulcerative Colitis
-on endoscopic remission vs placebo in subjects with Moderate to Severe Active Ulcerative Colitis.
-on clinical remission and response vs placebo in subjects with Moderate to Severe Active Ulcerative Colitis.
-on Quality of Life (QoL) measured by the SF-36 questionnaire vs placebo in subjects with Moderate to Severe Active Ulcerative Colitis.
- to assess pharmacokinetic parameters in subjects.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

-Men or women age 18 - 75 years;

- Diagnosis of moderate to severe active UC confirmed by endoscopy and histology at least 12 weeks prior to screening visit. Moderate to severe active UC defined by Mayo Clinic Score (MCS) of 6 to 12 inclusive (on a scale of 0-12). Moderate to severe active UC should be confirmed at screening visit with a centrally read MCS endoscopy score of at least 2 (on a scale of 0-3);

-Subjects receiving oral corticosteroids must have been on a stable dose of prednisone or prednisone equivalent ≤20 mg/day) or on beclomethasone diproprionate (≤5mg/day) or on budesonide MMX (≤9mg/day), for ≥2 weeks before the screening visit;

-Topical corticosteroids and topical 5-aminosalicylic acid preparations must have been withdrawn ≥2 weeks before the screening visit;
-Subjects who are on oral 5-aminosalicylic acid must have been on a stable dose ≥4 weeks before the screening visit;

-Subjects who are receiving immunosuppressants in the form of azathioprine, 6-mercaptopurine, or methotrexate needed to be on a stable dose for 4 weeks before the screening visit. Subjects taking methotrexate also are advised to take folic acid 1 mg/day (or equivalent) supplementation if there is no contraindication;

-Subjects on probiotics (e.g., Culturelle® [Lactobacillus GG, i-Health, Inc.], Saccharomyces boulardii) must be on stable doses for 2 weeks before the screening visit;

-Subjects on antidiarrheals (e.g., loperamide, diphenoxylate with atropine) must be on stable doses for 2 weeks before the screening visit;

-Subjects who have previously received anti-tumor necrosis factor (TNF) therapy or vedolizumab must have discontinued therapy ≥8 weeks before the screening visit;

-Subjects previously treated with cyclosporine or tacrolimus must have discontinued therapy ≥4 weeks before the screening visit;
-Subjects previously treated with tube feeding, defined formula diets, or parenteral alimentation/nutrition must have discontinued treatment 3 weeks before the screening visit;

-Subjects with hematological and biochemical laboratory parameters as follows and within 14 days of baseline:
o Hemoglobin > 9.0 g dL-1;
o Absolute neutrophil count ≥ 750 mm-3;
o Platelets ≥ 100,000 mm-3;
o Total serum creatinine ≤ 1.3 x ULN (upper limit of normal);
o Creatinine clearance > 50 mL min-1 by the
Cockcroft-Gault equation within 60 days of entry;
o Total serum bilirubin < 1.5 x ULN;
o Alkaline phosphatase, AST (SGOT) and ALT (SGPT) < 1.5 x
ULN;

-Subjects should be able and willing to comply with study visits and procedures as per protocol;

-Subjects should understand, sign and date the written voluntary informed consent form at the screening visit prior to any protocol-specific procedures being performed;

-Subjects should be affiliated to a social security regimen (for French sites only);

-Females and males receiving the study treatment and their partners must agree to use a highly effective contraceptive method during the study and for 3 months after end of study or early termination. Contraception should be in place at least 2 weeks prior to study participation. Women must be surgically sterile or if of childbearing potential must use a highly effective contraceptive method. Women of childbearing potential (WOCBP) will enter the study after confirmed menstrual period and a negative pregnancy test. Highly effective methods of contraception include true abstinence, intrauterine device (IUD) or hormonal contraception associated with inhibition of ovulation, intrauterine hormone releasing system, bilateral tubal occlusion, vasectomized partner. True abstinence is defined when this is in line with the preferred and usual lifestyle of the subject. In each case of delayed menstrual period (over one month between menstruations) confirmation of absence of pregnancy is required. This recommendation also applies to WOCBP with infrequent or irregular menstrual cycle.

E.4

Principal exclusion criteria

-Subject with Crohn's Disease (CD), indeterminate colitis (IC) or presence or history of fistula with CD;

-History of toxic megacolon, abdominal abscess, symptomatic colonic stricture or stoma; history or is at imminent risk of colectomy;

-History or current evidence of colonic dysplasia or adenomatous colonic polyps. Subject with severe gastrointestinal complications; e.g., short bowel syndromes, obstructing strictures, recent or planned bowel surgery, Ileostomy and/or colostomy, recent bowel perforation;
-Subject with significant and known active infections at screening such as Infected abscess, positive for Clostridium difficile (stool antigen and toxin), CMV, TB and recent infectious hospitalization;

- Acute, chronic or history of clinically relevant pulmonary, cardiovascular, hepatic, pancreatic or renal functional abnormality, encephalopathy, neuropathy or unstable CNS pathology, angina or cardiac arrhythmias, or any other clinically significant medical problems as determined by physical examination and/or laboratory screening tests and/or medical history;

-Acute, chronic or history of immunodeficiency or autoimmune disease;

- History of malignancy unless there has been surgical excision that is considered to have achieved cure;

- Active malignancy that may require chemotherapy or radiation therapy;

- Seizure disorder or any history of prior seizure;

- Serious illness requiring systemic treatment and/or hospitalization within 3 weeks prior to baseline;

- Pregnant or breast-feeding woman;

- Active drug or alcohol abuse or dependence;

- Use of any investigational or non-registered product within 3 months preceding baseline;

- Any condition, which in the opinion of the investigator, could compromise the subject's safety or adherence to the study protocol.

E.5 End points

E.5.1

Primary end point(s)

Number of incidences of treatment-emergent adverse events in the ABX464 treated subjects compared to placebo.

E.5.1.1

Timepoint(s) of evaluation of this end point

Timepoint of evaluation of this end point from day 0 to EoS.

E.5.2

Secondary end point(s)

1.The change from screening in IL-22 expression levels in serum and rectal/sigmoidal tissue at week 8 compared to placebo.
2.The change from baseline in microRNA-124 levels in whole blood (PAXgene®) and in tissue (RNA later) at week 4 and week 8 compared to placebo.
3.The change from baseline in fecal calprotectin levels at week 4 and week 8 compared to placebo.
4.The change from screening in the histopathology/infiltrate (rectal/sigmoidal biopsies) assessed by the Geboes score at week 8 compared to placebo.
5.The change from screening in rectal microbiota using taxonomic markers at week 8 compared to placebo
6.The change from screening in Total Mayo Score in subjects receiving ABX464 at week 8 compared to placebo.
7.The change from baseline in Partial Mayo Score in subjects receiving ABX464 at week 4 and week 8 compared to placebo.
8.The proportion of subjects receiving ABX464 with clinical remission according to the Total Mayo Score at week 8 compared to placebo. Remission exclude friability and is based on total Mayo score ≤ 2 with no individual sub-score > 1.
9.The proportion of subjects achieving endoscopic remission at week 8. Endoscopic remission is defined as a Mayo endoscopic sub-score of 0.
10.The proportion of subjects achieving improvement in endoscopic appearance at week 8. Improvement of endoscopic appearance is defined as a Mayo endoscopic sub-score of ≤ 1.
11.The proportion of subjects achieving a symptomatic remission at week 8. Symptomatic remission is defined as a total Mayo Score ≤ 2 with no individual sub-score > 1 and rectal bleeding and stool frequency sub-scores of 0.
12.The time to UC worsening after week 8.
13.The serum concentration evaluation of ABX464 and its metabolites levels.
14.The scores and changes from baseline in SF-36 Questionnaire scores at week 4 and week 8.
15.The number of incidences of treatment-emergent serious adverse events.
16.The number of incidences of treatment-emergent adverse events of special interest.
17.The number of incidences of adverse events leading to investigational product discontinuation.
18.The number of incidences of specific laboratory abnormalities.

E.5.2.1

Timepoint(s) of evaluation of this end point

1. At week 8 compared to placebo.
2. At week 4 and week 8 compared to placebo.
3. At week 4 and week 8 compared to placebo.
4. At week 8 compared to placebo.
5. At week 8 compared to placebo.
6. At week 8 compared to placebo.
7.At week 4 and week 8 compared to placebo.
8.At week 8 compared to placebo.
9.At week 8.
10. At week 8.
11. At week 8.
12. After week 8.
13. As per metabolite levels.
14. At week 4 and week 8.
15. Throughout the study.
16. Throughout the study.
17. Throughout the study.
18. Throughout the study.

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

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

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

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

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

E.8.6.2

Trial being conducted completely outside of the EEA

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

LVLS

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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)

Normal standard of care.

Norme normale de soins.

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

2017-09-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-11-07

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2018-07-25

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