Clinical Trials Register

Summary
EudraCT Number:	2011-000241-21
Sponsor's Protocol Code Number:	BEL114870
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2011-05-25
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

UK - MHRA

A.2

EudraCT number

2011-000241-21

A.3

Full title of the trial

A clinical and mechanistic proof of efficacy study with belimumab in chronic immune thrombocytopenia (ITP) patients

A.3.1

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

A study to investigate belimumab for the treatment of chronic immune thrombocytopenia

A.4.1

Sponsor's protocol code number

BEL114870

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	GlaxoSmithKline Research & Development Limited
B.1.3.4	Country	United Kingdom
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	GlaxoSmithKline Research & Development Limited
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	GlaxoSmithKline
B.5.2	Functional name of contact point	GSK Clinical Support Helpdesk
B.5.3	Address:
B.5.3.1	Street Address	Iron Bridge Road, Stockley Park West
B.5.3.2	Town/ city	Uxbridge, Middlesex
B.5.3.3	Post code	UB11 1BT
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+44(0)208990 4466
B.5.5	Fax number	+44(0)208990 4968
B.5.6	E-mail	GSKClinicalSupportHD@gsk.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	BENLYSTA® (belimumab)
D.2.1.1.2	Name of the Marketing Authorisation holder	Human Genome Sciences Inc.
D.2.1.2	Country which granted the Marketing Authorisation	United States
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	belimumab
D.3.2	Product code	GSK1550188
D.3.4	Pharmaceutical form	Powder 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	belimumab
D.3.9.1	CAS number	356547-88-1
D.3.9.2	Current sponsor code	GSK1550188
D.3.9.3	Other descriptive name	Lymphostat B
D.3.9.4	EV Substance Code	SUB25607
D.3.10	Strength
D.3.10.1	Concentration unit	mg/kg milligram(s)/kilogram
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)	Yes
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Chronic Immune Thrombocytopenia

E.1.1.1

Medical condition in easily understood language

Immune thrombocytopenia (ITP)

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	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10051057
E.1.2	Term	Idiopathic thrombocytopenia
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 whether belimumab can demonstrate clinical efficacy in ITP
- To evaluate whether belimumab can modulate anti-platelet autoantibodies in patients with detectable baseline levels of these antibodies

E.2.2

Secondary objectives of the trial

- To evaluate the safety and tolerability of belimumab 10mg/kg in ITP
- To assess the pharmacokinetics of belimumab 10mg/kg in ITP
- To evaluate whether belimumab can modulate antigen specific lymphocyte responses, general serum autoantibody levels, serum cytokine/chemokine levels and transcriptomic profiling
- To evaluate whether any demonstrated modulation of B cells and the immune system can, through selected pharmacodynamic (PD) assays, be directly linked to clinical efficacy such that the PD assays could be used as biomarkers

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Age & gender: Male or female between 18 and 75 years of age inclusive, at the time of signing the informed consent
2. Disease severity: Diagnosis of chronic ITP for a minimum of 6 months with a platelet count of ≤75,000/μL at screening and a historical platelet count of ≤75,000/μL 2 to 6 months prior to screening.
3. ITP treatment: ITP patients stable either on no treatment or on a stable dose of corticosteroids (10mg/day prednisone or prednisone equivalent or less) and/or azathioprine (100mg/day or less) for a minimum of 30 days before screening.
4. ECG: Single QTc, < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block.
5. Female subject: A female subject is eligible to participate if she is not pregnant or nursing and at least one of the following conditions apply:
a. Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol < 40 pg/ml (<147 pmol/L) is confirmatory]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods in Section 8.1.1 if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.
b. Child-bearing potential and agrees to use one of the contraception methods listed in Section 8.1.1 for one month (2 weeks for abstinence) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until 16 weeks after the last dose.
6. Informed consent: Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

E.4

Principal exclusion criteria

1. Secondary ITP: If the diagnosis of ITP is secondary to other conditions.
2. B-cell Prior Therapy: Have received treatment with any B cell targeted therapy at any time.
3. 364 Day Prior Therapy: Have received any of the following within 364 days prior to Day 0:
• Abatacept.
• A biologic investigational agent other than B cell targeted therapy.
4. 180 Day Prior Therapy: Have received any of the following within 180 days prior to Day 0:
• Intravenous (IV) cyclophosphamide.
• 3 or more courses of systemic corticosteroids for concomitant conditions (eg, asthma, atopic dermatitis. Topical or inhaled steroids are permitted).
5. 90 Day Prior Therapy: Have received any of the following within 90 days prior to Day 0:
• High dose corticosteroid for treatment of ITP (> 100 mg/day prednisone or equivalent).
• Splenectomy, plasmapheresis.
6. 60 Day Prior Therapy: Have received any of the following within 60 days, 5 halflives or twice the duration of the biological effect of the investigational product (whichever is longer) prior to Day 0:
• A non-biologic investigational agent.
• Any other immunosuppressive/immunomodulatory agent with the exception of azathioprine and corticosteroids.
• Eltrombopag, romiplostim.
• Any steroid injection.
Note: Inhaled steroids and Topical immunosuppressive agents are allowed.
7. 30 Day Prior to Screening Therapy: Have received any of the following within 30 days prior to Screening:
• Intravenous immunoglobulin.
• Corticosteroids greater than 10mg/day or azathioprine more than 100 mg/day.
• Changes to corticosteroid or azathioprine therapy.
8. 30 Day Prior Therapy: Have received any of the following within 30 days prior to Day 0:
• A live vaccine.
9. Haemorrhage: Disease status where, in the opinion of the investigator, the subject could be at risk of haemorrhage that threatens a vital organ.
10. Transplantation: Have a history of a major organ transplant or hematopoietic stem cell/marrow transplant.
11. Cancer: Have a history of malignant neoplasm within the last 5 years, except for adequately treated cancers of the skin or carcinoma in situ of the uterine cervix.
12. Acute or chronic infection: Have required management of acute or chronic infections, as follows:
• Currently on any suppressive therapy for a chronic infection
• Hospitalisation for treatment of infection within 60 days prior to Day 0.
• Use of parenteral antibiotics within 60 days prior to Day 0.
13. Other diseases/conditions: Have clinical evidence of significant unstable or uncontrolled acute or chronic diseases not due to ITP which, in the opinion of the investigator, could confound the results of the study or put the subject at undue risk.
or
Have a planned surgical procedure or a history of any other medical disease, laboratory abnormality, or condition that, in the opinion of the investigator, makes the subject unsuitable for the study.
14. Hepatitis: A positive screening Hepatitis C antibody result or serologic evidence of
Hepatitis B (HB) infection based on the results of testing for HBsAg, anti-HBc and anti-HBs as follows:
• Patients positive for HBsAg are excluded.
• Patients negative for HBsAg and anti-HBc antibody but positive for anti-HBs antibody and with no history of Hepatitis B vaccination are excluded.
• Patients negative for HBsAg but positive for both anti-HBc and anti-HBs
antibodies are excluded.
• Patients negative for HBsAg and anti-HBs antibody but positive for anti-HBc antibody are excluded.
15. HIV: A positive test for HIV antibody at screening or historically.
16. Liver Function Tests: Aspartate aminotransferase (AST) and alanine
aminotransferase (ALT) ≥ 2x upper limit of normal (ULN); alkaline phosphatase and
bilirubin > 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
17. Immunodeficiency: Have an IgA deficiency (IgA < 10mg/dL).
18. Laboratory Abnormalities: Abnormal laboratory assessments which are judged clinically significant by the investigator.
19. Lymphopenia: Have a lymphocyte count <500 per mm3.
20. Drug Sensitivity: History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy including a previous anaphalactic reaction to parenteral administration contrast agents, human or murine
proteins or monoclonal antibodies, that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
21. Suicidality: Subjects, who have evidence of serious suicide risk including any history of suicidal behavior in the last 6 months and/or any suicidal ideation of type 4 or 5 on the C-SSRS in the last 2 months or who in the investigator's judgment, pose a significant suicide risk.
22. Substance Abuse: Evidence of current drug or alcohol abuse or dependence.
23. Blood donation: Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.

E.5 End points

E.5.1

Primary end point(s)

- Change from baseline in platelet count
- Change from baseline in serum and platelet-bound GPIIb/IIIa and/or GPIb/IX autoantibodies (in patients with detectable baseline levels of these antibodies)

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 28

E.5.2

Secondary end point(s)

Efficacy
- Time to first response (platelet count increase >20,000/µL from baseline)
- Incidence of response of platelet count increase >20,000/µL from baseline (Day 0) at week 28
- Incidence of complete response as defined by platelet count to >100,000 at week 28
- Incidence of subjects with ≥ 2 times baseline platelet count at week 28

Safety and tolerability
- Adverse Events (AEs)
- Change from baseline and number of subjects outside the normal range for blood pressure, heart rate, temperature
- Change from baseline in clinical chemistry and haematology parameters
- Immunogenicity

Pharmacokinetics
- Individual serum concentrations of belimumab and data permitting summary PK parameters

Pharmacodynamics/biomarkers
- Change in serum and/or platelet bound anti-platelet antibodies by visit
- Change in relevant B cell and T cell sub-populations and BLyS receptor expression (by FACS analysis) by visit
- Change in antigen-specific B cells and T cells by visit
- Serum cytokine/chemokine and autoantibody profile by visit
- Change in transcriptomic profile by visit

E.5.2.1

Timepoint(s) of evaluation of this end point

Weeks 0, 2, 4, 8, 12, 16, 20, 24, 28, 40, 52 (dependent on endpoint)

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

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

Yes

E.8.1.4

Double blind

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

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

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’s last safety visit (16 week post last dose)

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