Clinical Trials Register

Summary
EudraCT Number:	2008-001241-26
Sponsor's Protocol Code Number:	Study 971
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:	2008-09-27
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

Bulgarian Drug Agency

A.2

EudraCT number

2008-001241-26

A.3

Full title of the trial

A randomized, placebo-controlled, double-blind, dose escalation study to evaluate the efficacy, safety and tolerability of the study drug BT971 in patients with rheumatoid arthritis receiving concomitant Methotrexate

A.4.1

Sponsor's protocol code number

Study 971

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Biotest AG
B.1.3.4	Country	Germany
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	BT061 (CD4 monoclonal antibody)
D.3.2	Product code	BT971
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Intravenous use Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	BT061
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	50
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	Yes
D.3.11.13.1	Other medicinal product type	biological product derived from recombinant organism

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 injection
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

Active rheumatoid arthritis, functional class II-III.

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	12.1
E.1.2	Level	LLT
E.1.2	Classification code	10039073
E.1.2	Term	Rheumatoid arthritis

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Efficacy, safety and tolerability of BT061 mab therapy in patients receiving concomitant Methotrexate (MTX)

E.2.2

Secondary objectives of the trial

N/A

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Female and male patients with active rheumatoid arthritis.
2. ACR criteria for diagnosis of RA, functional class II-III.
3. Active RA as defined by:
• ≥ 6 swollen joints on 66 joint count.
• ≥ 6 tender joints on 68 joint count.
• ≥ 2 of the following: Erythrocyte Sedimentation Rate (ESR) ≥ 28 mm/h, morning stiffness ≥ 45 min., C-reactive Protein (CRP) ≥ 20 mg/L.
4. Age limitations of ≥ 18 years and ≤ 75 years.
5. Body mass index (BMI) between 18 and 30 kg/m2 inclusive, with a body weight between 50 - 110 kg.
6. At least one traditional DMARD inadequate response despite ≥ 3 months of treatment.
7. Concurrent RA medications with stable doses of oral MTX for ≥ 6 months before enrollment (15 to 20 mg per week or as low as 10 mg per week for patients unable to tolerate higher doses). Dose of MTX must be kept constant during study duration (treatment period and follow-up period).
8. Concomitant medication with oral corticosteroids is allowed if stable dose of max. 10 mg (equivalent to prednisone) per day for ≥ 4 weeks prior to Screening.
9. Concomitant medication with NSAIDs is allowed if stable dose for ≥ 4 weeks prior to Screening.
10. No acute or relevant abnormalities in ECG.
11. Laboratory results:
• Hemoglobin: ≥ 8.5 g/Dl.
• Hematocrit: > 30%.
• White Blood Cells (WBC): ≥ 3.5 x 109 cells/L.
• CD4 count: > 0.4 x 109 cells/L.
• Neutrophils: ≥ 1.5 x 109 cells/L.
• Platelets: ≥ 150 x 109 cells/L.
• Serum transaminases (ALAT, ASAT): ≤ 3 times the upper limit of normal.
• Bilirubin: < 3 mg/Dl.
• Alkaline phosphatase: ≤ 2 times the upper limit of normal.
• Urea nitrogen: < 1.5 times the upper limit of normal.
12. B-cell count: ≥ 75% of the lower limit of normal.
13. Signed and dated written informed consent.

E.4

Principal exclusion criteria

1. Pre- and concomitant treatment with DMARDs other than Methotrexate, biological product(s), and intraarticular, intramuscular, or intravenous corticosteroids during the last 4 weeks prior to study inclusion and during the entire study.
2. Previous therapy with CD4 mab (note, that a patient who took participation in Step 1 should not be enrolled in Step 2, since this patient has already been treated with BT971).
3. Therapy with Adalimumab or Infliximab in the last 8 weeks and therapy with Etanercept in the last 4 weeks prior to study inclusion and during the entire study.
4. Therapy with Rituximab in the last 6 months prior to study inclusion and during the entire study.
5. Known therapy with Abatacept.
6. Kidney insufficiency as defined by creatinine clearance: < 60 ml/min (Cockcroft Gault equation).
7. History of severe allergic or anaphylactic reaction to proteins of human origin (e.g., vaccination reaction).
8. Known malignancy or history of malignancy within the previous 5 years with no evidence of recurrence.
9. History of clinically significant major disease, i.e., severe heart/lung disease NYHA ≥ 3 (New York Heart Association: class III: patients with marked limitation of activity; comfortable only at rest), autoimmune disease.
10. Serious local (e.g., abscess) or systematic infection (e.g., pneumonia, septicaemia) within previous 3 months.
11. Vaccinated with live, live attenuated, and/or killed vaccines in the previous 3 months prior to the first administration of the study drug.
12. Positive diagnosis for acute or chronic infections (i.e., HBV, HCV, HIV).
13. History of positive diagnosis for active tuberculosis.
14. History of or recurrent acute inflammatory joint disease other than RA.
15. Known immune deficiency.
16. History of lymphoproliferative disease, including lymphoma and lymphadenopathy.
17. History of clinically significant drug or alcohol abuse.
18. The patient, planned to be enrolled is an employee of any involved study investigator or any involved institution including the study sponsor.
19. Joint surgery within 2 months prior to Screening.
20. Pregnant or nursing women, or woman of childbearing potential who are not using an effective contraceptive method during the study and at least four months after the last administration of study drug (e.g., oral or injectable contraceptives, intrauterine devices, double-barrier method, contraceptive patch, female sterilization, or condoms). Male patients should also maintain reliable contraceptive methods during the entire study participation and at least four months after the last study drug administration.
21. Participation in another clinical trial within 90 days before entering the study or during the study.
22. Inability or lacking motivation to participate in the study.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint of this study is the ACR 20 response after 8 weeks (Week 9, Visit 9, Day 57±2) of treatment with:
1. 0.5 mg BT061 IV + MTX PO or parenteral, 2.0 mg BT061 IV + MTX PO or parenteral, or placebo IV + MTX PO or parenteral for Step 1
and
2. 50 mg BT061 SC + MTX PO or Placebo SC + MTX PO for Step 2

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

Yes

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

E.8.1.4

Double blind

Yes

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.8.3

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

Information not present in EudraCT

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

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

LPLV

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	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	13
F.4.2	For a multinational trial
F.4.2.1	In the EEA	110
F.4.2.2	In the whole clinical trial	110

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

2008-07-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2008-08-14

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

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