Clinical Trials Register

Summary
EudraCT Number:	2020-003880-24
Sponsor's Protocol Code Number:	ACT16832
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-12-14
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Germany - PEI

A.2

EudraCT number

2020-003880-24

A.3

Full title of the trial

A multicenter, open-label, non-randomized, Phase 1b/2 study to evaluate the safety, pharmacokinetics,and efficacy of subcutaneous isatuximab in adults with warm autoimmune hemolytic anemia

A.3.1

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

Safety, pharmacokinetics, and efficacy of subcutaneous isatuximab in adults with warm autoimmune
hemolytic anemia

A.4.1

Sponsor's protocol code number

ACT16832

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1255-5350

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	Sanofi-Aventis Recherche & Developpement
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	Sanofi-Aventis Recherche & Développement
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	Sanofi-Aventis Deutschland GmbH
B.5.2	Functional name of contact point
B.5.3.4	Country	Germany
B.5.6	E-mail	medinfo.de@sanofi.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	Isatuximab
D.3.2	Product code	SAR650984
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Isatuximab
D.3.9.3	Other descriptive name	SAR650984
D.3.9.4	EV Substance Code	SUB119676
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	140
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)	Yes
	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	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

Warm autoimmune hemolytic anemia

E.1.1.1

Medical condition in easily understood language

Blood and lymphatic diseases

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	PT
E.1.2	Classification code	10047822
E.1.2	Term	Warm type haemolytic anaemia
E.1.2	System Organ Class	10005329 - Blood and lymphatic system disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

• Part A: To evaluate the safety and tolerability of subcutaneous injections of isatuximab in adults
with wAIHA
• Part B: To evaluate the efficacy of the selected dose in adults with wAIHA

E.2.2

Secondary objectives of the trial

Part A (Cohorts 2 and 3 only)
-To evaluate the efficacy of isatuximab in adults with wAIHA
-To evaluate the durability of response to isatuximab and time to response
-To evaluate the impact of isatuximab treatment on fatigue
• Part B
-To evaluate the safety and tolerability of isatuximab in adults with wAIHA
-To evaluate the durability of response to isatuximab and time to response
-To evaluate the impact of isatuximab treatment on fatigue
• Parts A (all Cohorts) and B
-To evaluate the effect of isatuximab on markers of hemolysis
-To characterize the pharmacokinetic profile of isatuximab in adults with wAIHA
-To evaluate the immunogenicity of isatuximab

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Participant must be ≥18 to years of age, inclusive, at the time of signing the informed
consent.
- Males and females with a confirmed diagnosis of primary w AIHA or systemic lupus
erythematosus (SLE)-associated w AIHA (without other SLE-related manifestations apart
from cutaneous and musculoskeletal manifestations) who meet the following criteria:
a) Hemoglobin level <10 g/dL at screening.
b) Hemolysis (haptoglobin ≤40 mg/dL and total bilirubin above the
upper limit of normal).
c) Positive direct antiglobulin test (DAT) (IgG or IgG + complement C3d pattern or IgM
warm autoantibodies (positive dual DAT)).
- Participants who have previously failed to maintain a sustained response after treatment
with corticosteroids (corticosteroid-refractory or corticosteroid-dependent primary wAIHA).
- Part A only: Participants who have previously failed to maintain a sustained response
after treatment with rituximab (or other anti-CD20 monoclonal antibodies). The last dose
of the anti-CD20 antibody must have been administered at least 12 weeks before
enrollment.
- Part B: Participants who have had an insufficient response to at least 1 prior therapy in
addition to corticosteroids (splenectomy is regarded as a prior therapy).
- Contraceptive use by men and women

E.4

Principal exclusion criteria

Participants are excluded from the study if any of the following criteria apply:
- Clinically significant medical history or ongoing chronic illness that
would jeopardize the safety of the participant or compromise the quality of the data derived from his or her participation in the study as determined by the Investigator.
- Serious infection that required hospitalization within 3 months prior to enrollment.
- Secondary wAIHA from any cause including drugs, lymphoproliferative disorders, infectious or autoimmune disease (SLE without other SLE related manifestations apart from cutaneous and musculoskeletal manifestations is allowed), or active hematologic malignancies.
Participants with positive antinuclear antibodies but without a definitive diagnosis of an autoimmune disease are allowed.
- History of coagulation or bleeding disorders (Evans Syndrome is
allowed).
- Uncontrolled or active HBV or HCV infection
- HIV infection.
- Serum gammaglobulin levels <3 g/L.
- Females who are pregnant, lactating, or considered unreliable with
respect to contraceptive practice.
- Concurrent treatment with corticosteroids, unless the participant has been on a stable daily dose for = 30 days prior to enrollment.
- Treatment with cyclophosphamide within 4 weeks prior to enrollment.
- Treatment with cytotoxic drugs (other than cyclophosphamide) within 12 weeks prior to enrollment.

E.5 End points

E.5.1

Primary end point(s)

Part A:To assess safety and tolerability
Standard clinical and laboratory parameters and adverse events
Part B
-To evaluate overall response rate (R) or complete response (CR) at Day 85.
R is defined as an increase in hemoglobin by =2 g/dL from baseline and an absence of transfusion in the last 7 days and absence of rescue medications in the past 4 weeks. Biochemical evidence of hemolysis may still be present.
CR is defined as hemoglobin =11 g/dL (women) or =12 g/dL (men), no
evidence of hemolysis (normal bilirubin, LDH, haptoglobin, and
reticulocytes), absence of transfusion in the last 7 days and absence of rescue medication in the past 4 weeks

E.5.1.1

Timepoint(s) of evaluation of this end point

Part A:Through Day 169
PartB:Through Day 85

E.5.2

Secondary end point(s)

1 - Part A (Cohorts 2 and 3 Only) : To evaluate overall response rate (R) or complete response (CR) at Day 85 ; R is defined as an increase in hemoglobin by =2 g/dL from baseline and an absence of transfusion in the last 7 days and absence of rescue medications in the past 4 weeks.
Biochemical evidence of hemolysis may still be present.
CR is defined as hemoglobin =11 g/dL (women) or =12 g/dL(men), no
evidence of hemolysis (normal bilirubin, LDH, haptoglobin, and
reticulocytes), and absence of transfusion in the last 7 days and absence of rescue medication in the past 4 weeks.
2 - Part A (Cohorts 2 and 3 Only) and Part B : Proportion of participants with durable hemoglobin response by Day 169 ; Durable response is defined as Hb level =10 g/dL with an increase from baseline of =2 g/dL on three consecutive evaluable visits during the study period; with absence of transfusion and no rescue medication during the period of 3 consecutive visits and for at least 7 days (transfusions) and 4 weeks (rescue medication) prior to the first consecutive visit.
3 - Part A (Cohorts 2 and 3 Only) and Part B : Overall response rate at
Day 169, median time to R or CR, median time to loss of R or CR,
proportion of participants requiring rescue therapy (any wAIHA-directed therapy other than prednisone or transfusion) or splenectomy ; Overall response rate at Day 169, median time to R or CR, median time to loss of R or CR (loss of R defined as hemoglobin <10 g/dL at two consecutive visits at least 7 days apart and initiation of new treatment for anemia or increase in steroid dose; loss of CR is defined as hemoglobin <11 g/dL (women) or <12 g/dL (men) at two consecutive visits at least 7 days apart), proportion of participants requiring rescue therapy (any wAIHAdirected therapy other than prednisone or transfusion) or splenectomy
4 - Part A (Cohorts 2 and 3 Only) and Part B : FACIT-fatigue scale score
5 - Part B : To assess safety and tolerability ; Standard clinical and
laboratory parameters and adverse events.
6 - Part A (All Cohorts) and B : Change from baseline in LDH
7 - Part A (All Cohorts) and B: Change from baseline in haptoglobin,
8 - Part A (All Cohorts) and B : Change from baseline in reticulocytes
9 - Part A (All Cohorts) and B : Change from baseline in total bilirubin
10 - Part A (All Cohorts) and B : PK parameters after subcutaneous
administrations (Cmax) ; Maximum concentration received after
injection (Cmax) and area under the plasma concentration versus time curve calculated over the dosing interval T (336 h) (AUC0-2week)
11 - Part A (All Cohorts) and B : PK parameters after subcutaneous
administrations (AUC0-2week) ; Area under the plasma concentration
versus time curve calculated over the dosing interval T (336 h) (AUC0-
2week)
12 - Part A (All Cohorts) and B : Incidence of anti-isatuximab antibodies
13 - Part A (All Cohorts) and B : Titer (if relevant) of anti-isatuximab
antibodies

E.5.2.1

Timepoint(s) of evaluation of this end point

Part A (Cohorts 2 and 3 Only):
1)Through Day 85
2 to 13 : Through Day 169

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

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

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)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

Phase I/II study

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

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.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the 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

United States

Belgium

France

Germany

Hungary

Italy

Netherlands

United Kingdom

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

Last Subject Last Visit

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

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)

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

2021-03-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-03-24

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2023-06-26

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials