Clinical Trials Register

Summary
EudraCT Number:	2022-001177-31
Sponsor's Protocol Code Number:	EFC16521
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2022-07-29
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

Belgium - FPS Health-DGM

A.2

EudraCT number

2022-001177-31

A.3

Full title of the trial

An open-label, single-arm, multicenter study to evaluate the efficacy and safety of caplacizumab and immunosuppressive therapy without first line therapeutic plasma exchange in adults with immune-mediated thrombotic thrombocytopenic purpura

A.3.1

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

Caplacizumab and immunosuppressive therapy without first line therapeutic plasma exchange in adults with immune-mediated thrombotic thrombocytopenic purpura

A.4.1

Sponsor's protocol code number

EFC16521

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1244-0426

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 et Développement
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	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Sanofi-Aventis Recherche & Développement
B.5.2	Functional name of contact point	Esther Beeks
B.5.3	Address:
B.5.3.1	Street Address	1 avenue Pierre Brossolette
B.5.3.2	Town/ city	Chilly-Mazarin
B.5.3.3	Post code	91385
B.5.3.4	Country	France
B.5.4	Telephone number	+31 (020)245 4000
B.5.6	E-mail	CTA.Belgium@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	Yes
D.2.1.1.1	Trade name	Cablivi®
D.2.1.1.2	Name of the Marketing Authorisation holder	Ablynx NV
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/09/629
D.3 Description of the IMP
D.3.1	Product name	Cablivi®
D.3.2	Product code	ALX0081
D.3.4	Pharmaceutical form	Powder and solvent for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Caplacizumab
D.3.9.1	CAS number	915810-67-2
D.3.9.2	Current sponsor code	ALX0081
D.3.9.3	Other descriptive name	Nanobody directed towards the human A1 domain of von Willebrand factor
D.3.9.4	EV Substance Code	SUB181150
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	12.5
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	Yes
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.IMP: 2
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	Cablivi®
D.2.1.1.2	Name of the Marketing Authorisation holder	Ablynx NV
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/09/629
D.3 Description of the IMP
D.3.1	Product name	Cablivi®
D.3.2	Product code	ALX0081
D.3.4	Pharmaceutical form	Powder and solvent for 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	Caplacizumab
D.3.9.1	CAS number	915810-67-2
D.3.9.2	Current sponsor code	ALX0081
D.3.9.3	Other descriptive name	Nanobody directed towards the human A1 domain of von Willebrand factor
D.3.9.4	EV Substance Code	SUB181150
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	12.5
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	Yes
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

Thrombotic Thrombocytopenic Purpura

E.1.1.1

Medical condition in easily understood language

Thrombotic Thrombocytopenic Purpura

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	10043648
E.1.2	Term	Thrombotic thrombocytopenic purpura
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

To evaluate the efficacy of caplacizumab in combination with immunosuppressive therapy (IST) without therapeutic plasma exchange (TPE) in adults with immune mediated thrombotic thrombocytopenic purpura (iTTP)

E.2.2

Secondary objectives of the trial

To evaluate:
- the need for therapeutic plasma exchange in adult participants with an episode of iTTP treated with caplacizumab and IST
- the safety of caplacizumab in combination with IST without 1st line TPE in adults with iTTP
- the effect of treatment with caplacizumab and IST without 1st line TPE on clinical response
- the effect of treatment with caplacizumab and IST without 1st line TPE on restoring platelet counts
- the effect of treatment with caplacizumab and IST without 1st line TPE on refractory disease
- the effect of treatment with caplacizumab and IST without 1st line TPE on clinically relevant iTTP-related events consisting of iTTP-related mortality
- the effect of treatment with caplacizumab and IST without 1st line TPE on clinically relevant iTTP-related events consisting of exacerbation of iTTP
- the effect of treatment with caplacizumab and IST without 1st-line TPE on clinically relevant iTTP-related events consisting of relapse of iTTP

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Participants with a clinical diagnosis of iTTP (initial or recurrent), which includes thrombocytopenia, microangiopathic hemolytic anemia (eg, presence of schistocytes in peripheral blood smear) and relatively preserved renal function. The iTTP diagnosis should be confirmed by ADAMTS13 testing within 48 hours (2 days).
Participants with a clinical diagnosis of iTTP and a French TMA score of 1 or 2.

A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:
Is a woman of nonchildbearing potential (WONCBP),
OR
Is a woman of childbearing potential (WOCBP) and agrees to use an acceptable contraceptive method during the overall treatment period and for at least 2 months after the last study drug administration.

Male participants with female partners of childbearing potential must agree to follow the contraceptive guidance as per protocol during the overall treatment period and for at least 2 months after last study drug administration.

E.4

Principal exclusion criteria

Platelet count ≥100 × 10^9/L..

Serum creatinine level >2.26 mg/dL (200 μmol/L) in case platelet count is >30 × 10^9/L. (to exclude possible cases of atypical HUS).

Known other causes of thrombocytopenia including but not limited to:
• Clinical evidence of enteric infection with E. coli 0157 or related organism.
• Atypical HUS.
• Hematopoietic stem cell, bone marrow or solid organ transplantation-associated thrombotic microangiopathy.
• Known or suspected sepsis.
• Diagnosis of disseminated intravascular coagulation.

Congenital TTP (known at the time of study entry).

Clinically significant active bleeding or known co-morbidities associated with high risk of bleeding (excluding thrombocytopenia).

Inherited or acquired coagulation disorders.

Malignant arterial hypertension.

Participants requiring or expected to require invasive procedures immediately (eg, stroke requiring thrombolytic therapy, those who need mechanical ventilation, etc.).

Those presenting with severe neurological or cardiac disease.

Clinical condition other than that associated with TTP, with life expectancy <6 months, such as end-stage malignancy.

Known chronic treatment with anticoagulants and anti-platelet drugs that cannot be stopped (interrupted) safely, including but not limited to:
• vitamin K antagonists.
• direct-acting oral anticoagulants.
• heparin or low molecular weight heparin (LMWH).
• non-steroidal anti-inflammatory molecules other than acetyl salicylic acid.

Participants who were previously enrolled in this clinical study (study EFC16521).

Participants who received an investigational drug, or device, other than caplacizumab, within 30 days of anticipated IMP administration or 5 half-lives of the previous investigational drug, whichever is longer.

Positive result on COVID test.

E.5 End points

E.5.1

Primary end point(s)

Proportion of participants achieving Remission without requiring therapeutic plasma exchange (TPE); Remission is defined as sustained Clinical Response (sustained platelet count ≥150 × 10^9/L and lactate dehydrogenase [LDH] <1.5 × upper limit of normal [ULN] and no clinical evidence of new or progressive ischemic organ injury for at least 2 consecutive visits) with either (a) no TPE and no anti- von Willebrand factor (anti-vWF) therapy for ≥30 days (Clinical Remission), or (b) with attainment of a disintegrin and metalloproteinase with a thrombospondin type 1 motif13 (ADAMTS13) ≥50% (Complete ADAMTS13 remission), whichever occurs first.

E.5.1.1

Timepoint(s) of evaluation of this end point

Overall study period from day 1 to day 168 (treatment period + 12 weeks of follow-up)

E.5.2

Secondary end point(s)

1. Proportion of participants achieving Remission
2. Proportion of participants who require TPE
3. The occurrence of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESIs)
4. Proportion of participants achieving Clinical Response; Clinical Response is defined as sustained platelet count ≥150 × 10^9/L and LDH <1.5 × ULN and no clinical evidence of new or progressive ischemic organ injury for at least 2 consecutive visits.
5. Proportion of participants achieving Clinical Response
6. Time to platelet count response; Platelet count response defined as time from start of treatment to initial platelet count ≥150 × 10^9/L that is sustained for ≥2 days
7. Proportion of participants refractory to therapy; Refractory to therapy defined as lack of sustained platelet count increment (over 2 consecutive days) or platelet counts <50 × 10^9/L and persistently elevated LDH (>1.5 × ULN) despite 5 days of treatment
8. Proportion of participants with TTP-related death
9. Proportion of participants with TTP-related death
10. Proportion of participants with a clinical exacerbation of iTTP; Clinical Exacerbation is defined as after a Clinical Response and before a Clinical Remission, platelet count decreases to <150 × 10^9/L (with other causes of thrombocytopenia excluded), with or without clinical evidence of new or progressive ischemic organ injury, within 30 days of stopping TPE or anti vWF therapy.
11. Proportion of participants with a clinical exacerbation of iTTP
12. Proportion of participants with a clinical relapse of iTTP; Clinical Relapse is defined as after a Clinical Remission, platelet count decreases to <150 × 10^9/L (with other causes of thrombocytopenia ruled out), with or without clinical evidence of new ischemic organ injury. A Clinical Relapse must be confirmed by documentation of severe ADAMTS13 deficiency (<10%).
13. Proportion of participants with a clinical relapse of iTTP

E.5.2.1

Timepoint(s) of evaluation of this end point

1. Overall study period from day 1 to day 168
2. On-treatment period from day 1 to day 84
3. Treatment-emergent (TE) period from day 1 to day 112
4. On-treatment period from day 1 to day 84
5. Overall study period from day 1 to day 168
6. From day 1 to day 168
7. On-treatment period from day 1 to day 84
8. On-treatment period from day 1 to day 84
9. Overall study period from day 1 to day 168
10. On-treatment period from day 1 to day 84
11. Overall study period from day 1 to day 168
12. On-treatment period from day 1 to day 84
13. Overall study period from day 1 to day 168

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

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)

Yes

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

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

Canada

Japan

United States

Switzerland

Austria

Belgium

Czechia

France

Germany

Greece

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

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

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

2022-08-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-10-20

P. End of Trial
P.	End of Trial Status	Trial now transitioned

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