Clinical Trials Register

Summary
EudraCT Number:	2019-003202-27
Sponsor's Protocol Code Number:	FAST-TOT401-19
National Competent Authority:	Bulgarian Drug Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-07-06
Trial 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

Bulgarian Drug Agency

A.2

EudraCT number

2019-003202-27

A.3

Full title of the trial

Assessment of the eFficacy, the onset-of-Action and the Safety of Tot'héma ® in adults with moderate iron deficiency anaemia

Оценка на ефикасността, началото на действие и безопасността на Тотема при възрастни с умерено тежка желязодефицитна анемия

A.3.1

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

Assessment of the eFficacy, the onset-of-Action and the Safety of Tot'héma ® in adults with moderate iron deficiency anaemia

A.3.2

Name or abbreviated title of the trial where available

FAST

A.4.1

Sponsor's protocol code number

FAST-TOT401-19

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	Laboratoire Innotech Internationnal
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	Laboratoire Innotech Internationnal
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	ICTA PM
B.5.2	Functional name of contact point	Clinical Trials information
B.5.3	Address:
B.5.3.1	Street Address	11 rue du Bocage
B.5.3.2	Town/ city	FONTAINE LES DIJON
B.5.3.3	Post code	21121
B.5.3.4	Country	France
B.5.4	Telephone number	+33380534096
B.5.6	E-mail	fast@icta.fr

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	Yes
D.2.1.1.1	Trade name	Tot'héma
D.2.1.1.2	Name of the Marketing Authorisation holder	LABORATOIRE INNOTECH INTERNATIONAL
D.2.1.2	Country which granted the Marketing Authorisation	Bulgaria
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.3.4	Pharmaceutical form	Oral solution in single-dose container
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Moderate iron deficiency anaemia

E.1.1.1

Medical condition in easily understood language

Moderate iron deficiency anemia

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

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	10002062
E.1.2	Term	Anaemia iron deficiency
E.1.2	System Organ Class	100000004851

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 assess, in patients with moderate IDA, the Onset-of-Action of a daily treatment with Tot'héma®.
The onset of action is defined as the time required for a mean increase of at least 0.5 g/dL from baseline in the haemoglobin level.

E.2.2

Secondary objectives of the trial

Assessment in patients with moderate IDA treated with Tot'héma:
-of the Onset-of-Action of Tot'héma, defined as the time required for a mean increase of at least 0.5g/dL from baseline in the haemoglobin (Hb) level, in each of the 2 geographic zones
-of the Onset-of-Action of Tot'héma®, defined as the time required for a mean increase of at least 2 g/dL from baseline in the Hb level
-of the proportion of patients achieving different levels of improvement and a normalization of Hb level
-of the time course of the increase and the normalization of Hb level
-of the evolution of biological markers of anaemia
-of the evolution of the mean level of C CRP
-of the evolution of fatigue in patients
-of the evolution of quality of life of patients
-performance of conjunctival pallor for detecting mIDA and its evolution during treatment
-of patient compliance with treatment
-of treatment safety
-of the overall level of investigators’ satisfaction with the treatment

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Selection criterion
1. Patient with moderate anaemia defined as 8 g/dL ≤ haemoglobin level ≤ 10 g/dL on the last hematological test performed within 7 days before screening visit

Inclusion criteria
1. Adult men and women (≥18 years)
2. Patient with a confirmation of moderate anaemia defined as 8 g/dL ≤ haemoglobin level ≤ 10 g/dL on the last hematological test performed within 7 days before inclusion visit
3. Patient with ferritin blood level < lower limit of laboratory standard for this biological parameter on the last hematological test performed within 7 days before inclusion visit
4. Patient who has read, understood, dated and signed the informed consent form
5. Patient agreeing to comply with protocol requirements, including visits and blood samples at specifically defined dates

E.4

Principal exclusion criteria

1. Patient for whom an oral iron supplementation is not indicated or not recommended according to Investigator’s opinion
2. C-Reactive Protein > 10 mg/L on the last hematological test performed within 7 days before inclusion visit
3. Patient with malignant neoplastic tumour
4. Patient presenting gastrointestinal disorders incompatible with study treatment compliance
5. Pregnant or breastfeeding woman
6. Woman with childbearing potential who does not agree to use an accepted highly effective method of contraception – per investigator’s judgment
7. Patient with surgery scheduled to occur during the treatment period
8. Patient allergic or hypersensitive to any of the components of Tot'héma® ampoule
9. Patient with chronic inflammatory disease, including chronic inflammatory bowel syndrome and/or chronic heart failure and/or chronic renal failure and/or inflammatory rheumatism
10. Patient with active digestive bleeding (such as digestive ulcer)
11. Patient having taken iron supplementation, iron-based IV therapy or mineral supplementation with iron within the 15 days prior to the inclusion visit (V2)
12. Patient with fructose intolerance, glucose-galactose malabsorption syndrome or sucrase-isomaltase deficiency
13. Patient with acute malaria crisis within 15 days prior to inclusion
14. Patient with a positive Faecal Occult Blood Test (FOBT)
15. Patient with HIV infection
16. Unreliable patients, including non-observant patients, patients with known alcoholism or drug abuse, or with a history of a serious psychiatric disorder, as well as patients who are reluctant to give informed consent or to comply with protocol requirement.
17. Patient with a family relationship to a person at the investigator’s site or at the Sponsor or at the CRO.
18. Participant involved in another interventional or observational clinical trial or who participated in another interventional clinical trial within four weeks before inclusion.

E.5 End points

E.5.1

Primary end point(s)

First time (in days) associated with a mean increase of the haemoglobin level of at least 0.5 g/dL (versus mean haemoglobin level at D0). This primary endpoint will be assessed by modelling the evolution during the treatment of the mean haemoglobin level between Day 0 and Week 12

E.5.1.1

Timepoint(s) of evaluation of this end point

Day0 (baseline), Day3, Day5, Day7, Day10, Day14, Day21, Day28, Day56, Day84

E.5.2

Secondary end point(s)

•First time (in days) associated with an increase in the mean haemoglobin level of at least 0.5 g/dL in patients of each geographic zone (versus mean haemoglobin level at baseline in Europe and Kenya) (Cf primary endpoint)
•First time (in days) associated with an increase in the mean haemoglobin level of at least 2 g/dL (versus mean haemoglobin level at baseline)
•Percentage of patients presenting an increase in Hb level ≥ 0.5g/dL (vs. baseline - D0) at each scheduled sampling time point
•Percentage of patients presenting an increase in Hb level ≥ 1 g/dL (vs. baseline - D0) at each scheduled sampling time point
•Percentage of patients presenting an increase in Hb level ≥ 2 g/dL (vs. baseline - D0) at each scheduled sampling time point
•Percentage of patients with a normalization of Hb levels at each scheduled sampling time point (Hb ≥ 12 g/dL for women, Hb ≥ 13 g/dL for men)
•Time to onset (in days) of a 0.5 g/dL increase in haemoglobin level (vs. baseline - D0)
•Time to onset (in days) of a 1 g/dL increase in haemoglobin level (vs. baseline - D0)
•Time to onset (in days) of a 2 g/dL increase in haemoglobin level (vs. baseline - D0)
•Time (in days) to normalization of haemoglobin levels (Hb ≥ 12 g/dL in women and Hb ≥ 13 g/dL in men)
•Mean haemoglobin level at each scheduled sampling time point and its evolution during treatment compared to baseline (D0)
•Mean reticulocytes level at each scheduled sampling time point and its evolution during treatment compared to baseline (D0)
•Mean levels of other relevant biological markers assayed at scheduled sampling time point (ferritin blood level, MCV, serum iron, T-SAT) and their evolution during treatment compared to baseline (D0)
•Mean CRP level at each scheduled sampling time point and its evolution during treatment compared to baseline (D0)
•Patient’s fatigue assessed by a Visual Analogue Scale (VAS) and by the FACIT-fatigue questionnaire, and its evolution during treatment compared to patient’s fatigue at baseline (D0)
•Patient’s quality of life (SF-36 questionnaire completed at baseline (D0) and at the end of the study (D84) and its evolution during treatment compared to questionnaire completed at baseline (D0)
•Cut-off value of haemoglobin level for conjunctival pallor accuracy in ruling in or out moderate IDA and evolution of conjunctival pallor during treatment
•Compliance with study treatment
•Treatment Emergent Adverse events (TEAE): Number of TEAE with relationship to treatment, severity, and seriousness,
•Number and percentage of patients experiencing each subtype of TEAE
•Percentage of patients with a dose reduction of the study treatment due to an adverse event
•Overall level of satisfaction of the investigators (satisfaction scale completed at V3, V4 and V5) and its evolution during treatment

E.5.2.1

Timepoint(s) of evaluation of this end point

D0: Hb, ferritin, MCV, serum iron, T-SAT, CRP, fatigue, FACIT-fatigue, SF-36, conjunctival pallor, safety
D3: Hb, MCV, serum iron, T-SAT, CRP
D5: Hb, MCV, serum iron, T-SAT, CRP
D7: Hb, ferritin, MCV, serum iron, T-SAT, CRP
D10: Hb, MCV, serum iron, T-SAT, CRP
D14: Hb, ferritin, MCV, serum iron, T-SAT, CRP, fatigue, FACIT-fatigue, conjunctival pallor, compliance, safety, investigators satisfaction
D21: Hb, ferritin, MCV, serum iron, T-SAT, CRP
D28: Hb, ferritin, MCV, serum iron, T-SAT, CRP, fatigue, FACIT-fatigue, conjunctival pallor, compliance, safety, investigators satisfaction
D56: Hb, ferritin, MCV, serum iron, T-SAT, CRP
D84: Hb, ferritin, MCV, serum iron, T-SAT, CRP, fatigue, FACIT-fatigue, SF-36, conjunctival pallor, compliance, safety, investigators satisfaction

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

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)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

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

E.8.2.3

Other

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

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

Kenya

France

Bulgaria

E.8.7

Trial has a data monitoring committee

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

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

121

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)

None

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

2020-07-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-06-02

P. End of Trial
P.	End of Trial Status	Completed

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