Clinical Trials Register

Summary
EudraCT Number:	2020-000761-16
Sponsor's Protocol Code Number:	ALXN1210-TMA-314
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:
Date on which this record was first entered in the EudraCT database:	2020-08-19
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

UK - MHRA

A.2

EudraCT number

2020-000761-16

A.3

Full title of the trial

A Phase 3, Open-label, Single Arm, Multicenter Study of Ravulizumab in
Addition to Best Supportive Care in Pediatric Participants (from 1 month to < 18 years of age)
with Thrombotic Microangiopathy (TMA) after Hematopoietic Stem Cell Transplantation
(HSCT)

A.3.1

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

Study of ravulizumab in pediatric participants with HSCT-TMA

A.3.2

Name or abbreviated title of the trial where available

Ravulizumab in Pediatric Participants with TMA after HSCT

A.4.1

Sponsor's protocol code number

ALXN1210-TMA-314

A.5.4

Other Identifiers

Name:

IND

Number:

128367

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	Alexion Pharmaceuticals, Inc.
B.1.3.4	Country	United States
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	Alexion Pharmaceuticals, 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	Alexion Europe SAS
B.5.2	Functional name of contact point	European Clinical Trial Information
B.5.3	Address:
B.5.3.1	Street Address	103-105 Rue Anatole France
B.5.3.2	Town/ city	Levallois-Perret
B.5.3.3	Post code	92300
B.5.3.4	Country	France
B.5.4	Telephone number	+33 147100615
B.5.5	Fax number	+33 147100611
B.5.6	E-mail	clinicaltrials.eu@alexion.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	Ultomiris
D.2.1.1.2	Name of the Marketing Authorisation holder	Alexion Europe SAS
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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Ultomiris
D.3.2	Product code	ALXN1210
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
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	RAVULIZUMAB
D.3.9.1	CAS number	1803171-55-2
D.3.9.2	Current sponsor code	ALXN1210
D.3.9.3	Other descriptive name	Ravulizumab
D.3.9.4	EV Substance Code	AS1
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	10
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

hematopoietic stem cell transplant-associated thrombotic microangiopathy

E.1.1.1

Medical condition in easily understood language

HSCT-TMA

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	10043645
E.1.2	Term	Thrombotic microangiopathy
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 assess the efficacy of ravulizumab plus BSC in the treatment of HSCT-TMA

E.2.2

Secondary objectives of the trial

Safety and tolerability of ALXN1210 and additional efficacy measures

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. 1 month of age up to < 18 years of age at the time of signing the informed consent
2. Participants who received HSCT within the past 6 months at the time of Screening
3. A TMA diagnosis, based on all of the following criteria occurring simultaneously:
• De novo thrombocytopenia or platelet transfusion refractoriness, where:
• De novo anemia or increase in transfusion requirements
• Either one of the following markers of hemolysis:
−Lactate dehydrogenase > 1.5 × ULN or,
− Presence of schistocytes ≥ 2 high power field (HPF)
• Proteinuria on spot urinalysis
• Presence of hypertension
4. Participants must have HSCT-TMA that persists for at least 72 hours after initial management of any triggering agent/condition
5.Body weight ≥ 5 kg at Screening
6. Male or female Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
7. Vaccinated against meningococcal infections if clinically feasible, according to institutional guidelines for immune reconstitution after HSCT. Participants must be re-vaccinated against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae if clinically feasible, according to institutional guidelines for immune reconstitution after HSCT. All participants should be administered coverage with prophylactic antibiotics according to institutional posttransplant infection prophylaxis guidances including coverage against N. meningiditis for at least 2 weeks after meningococcal vaccination. Participants who cannot receive meningococcal vaccine should receive antibiotic prophylaxis coverage against N. meningiditis the entire Treatment Period and for 8 months following the final dose of ravulizumab.
8. Participants or their legally authorized representative must be capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent or assent form and in this protocol

E.4

Principal exclusion criteria

1. Known familial or acquired ‘a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13’ (ADAMTS13) deficiency (activity < 5%)
2. Known Shiga toxin-related hemolytic uremic syndrome (ST-HUS)
3. Positive direct Coombs test
4. Diagnosis or suspicion of disseminated intravascular coagulation (DIC)
5. Known bone marrow/graft failure
6. Diagnosis of veno-occlusive disease (VOD)
7. Human immunodeficiency virus (HIV) infection (evidenced by HIV-1 or HIV-2 antibody titer,
8. Unresolved meningococcal disease
9. Presence or suspicion of sepsis (treated or untreated) within 7 days prior to Screening
10. Pregnancy or breastfeeding
11. Hypersensitivity to murine proteins or to 1 of the excipients of ravulizumab
12. Previously or currently treated with a complement inhibitor

E.5 End points

E.5.1

Primary end point(s)

TMA response

E.5.1.1

Timepoint(s) of evaluation of this end point

Throughout 26 Weeks

E.5.2

Secondary end point(s)

1. Time to TMA response
2. Change from baseline in TMA-associated organ dysfunctiond in renal system, cardiovascular system, pulmonary system, CNS, and GI system at 6 months and 1 year
3. TMA relapse during the study
4. Overall survival at 6 months and 1 year
5. Non-relapse mortality (
6. Platelet response
7. Hematologic response

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 26 and Week 52

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

Yes

E.6.13.1

Other scope of the trial description

Immunogenicity, biomarker, characterization

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.8.2.4

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

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

France

Germany

Italy

Japan

Korea, Republic of

Spain

United Kingdom

United States

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

Yes

F.1.1