Clinical Trials Register

Summary
EudraCT Number:	2013-005487-26
Sponsor's Protocol Code Number:	AI468-038
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:	2015-07-20
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

2013-005487-26

A.3

Full title of the trial

A Phase 2b Randomized, Active-Controlled, Double-Blind Trial to Investigate Safety, Efficacy and Dose-response of BMS-955176, Given on a Backbone of Tenofovir/Emtricitabine, in Treatment-Naive HIV-1 Infected Adults

A.3.1

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

Study to find at least one dose of BMS-955176 that will be safe, effective and tolerable in HIV-1 infected treatment naive adults

A.3.2

Name or abbreviated title of the trial where available

Dose-finding study of BMS-955176 in HIV-1 Infected treatment-naive adults

A.4.1

Sponsor's protocol code number

AI468-038

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1161-2094

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	Bristol-Myers Squibb International Corporation
B.1.3.4	Country	Belgium
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	Bristol-Myers Squibb International Corporation
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	Bristol-Myers Squibb International Corporation
B.5.2	Functional name of contact point	GCT-SU
B.5.3	Address:
B.5.3.1	Street Address	Parc de l'Alliance - Avenue de Finlande, 4
B.5.3.2	Town/ city	Braine-l'Alleud
B.5.3.3	Post code	1420
B.5.3.4	Country	Belgium
B.5.6	E-mail	clinical.trials@bms.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	NA
D.3.2	Product code	BMS-955176
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	N/A
D.3.9.2	Current sponsor code	BMS-955176-03
D.3.9.4	EV Substance Code	SUB33206
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	60
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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	No
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	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	NA
D.3.2	Product code	BMS-955176
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	N/A
D.3.9.2	Current sponsor code	BMS-955176-03
D.3.9.4	EV Substance Code	SUB33206
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	120
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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	No
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: 3
D.1.2 and D.1.3	IMP Role	Comparator
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	Sustiva
D.2.1.1.2	Name of the Marketing Authorisation holder	Bristol-Myers Squibb Pharma EEIG
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	Sustiva
D.3.2	Product code	BMS-561525
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Efavirenz
D.3.9.1	CAS number	154598-52-4
D.3.9.3	Other descriptive name	EFAVIRENZ
D.3.9.4	EV Substance Code	SUB06463MIG
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	600
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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	No
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	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 3
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

HIV

E.1.1.1

Medical condition in easily understood language

HIV

E.1.1.2

Therapeutic area

Diseases [C] - Virus Diseases [C02]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.0
E.1.2	Level	LLT
E.1.2	Classification code	10068341
E.1.2	Term	HIV-1 infection
E.1.2	System Organ Class	100000004862

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate antiviral efficacy of 3 doses (60, 120 and 180 mg) of BMS-955176, and EFV, each when given in combination with TDF/FTC in treatment-naïve subjects by determining the proportion of treatment-naïve subjects with plasma HIV-1 RNA < 40 c/mL at Week 24

E.2.2

Secondary objectives of the trial

- To assess the antiviral efficacy of BMS-955176 and EFV by determining the proportion of subjects with plasma
HIV-1 RNA < 40 c/mL at Weeks 48, and 96
- To assess the antiviral efficacy of BMS-955176 and EFV by determining the proportion of subjects with plasma
HIV-1 RNA < 200 c/mL at Weeks 24, 48, and 96
- To assess the emergence of HIV drug resistance among samples selected for drug resistance testing
- To assess efficacy of BMS-955176 and EFV, by using mean changes from baseline in log10 HIV-1 RNA, CD4+ T-cell counts, and percentage of CD4+ T-cells
- To assess the safety and tolerability of BMS-955176 in treatment-naïve subjects by measuring frequency of SAEs and AEs leading to discontinuation
- To assess disease progression as measured by the occurrence of new AIDS defining events (CDC Class C events)
- To characterize the pharmacokinetics of BMS-955176 when co-administered with TDF and FTC in treatment-naïve HIV-1 infected subjects.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

1- Pharmacogenetics Blood Sample Amendment 01 dated 28-January-2015, version 1.0:
The objective of this Amendment is to permit the collection and storage of blood samples for use in future exploratory pharmacogenetic research. Bristol-Myers Squibb will use DNA obtained from the blood sample and health information collected from the main clinical trial, AI468038 to study the association between genetic variation and drug response. Bristol-Myers Squibb may also use the DNA to study the causes and further progression of HIV. Samples from this study may also be used in conjunction with pharmacogenetic research results from other clinical studies to accomplish this objective.

2- Optional Week 2 Intensive PK Substudy:
Subjects with anemia, defined as Hemoglobin < 11.0 g/dL, should be excluded from participation in the Week 2 Intensive PK Substudy.
Subjects in all arms will have the opportunity to participate in an elective Intensive PK Substudy visit at Week 2 (window for visit: Day 12-16). Approximately 48 subjects, 12 subjects from each arm, are expected to participate in the substudy; BMS may allow the substudy to over-enroll in an effort to have a sufficient number of complete datasets.

E.3

Principal inclusion criteria

- Men and non-pregnant women, at least 18 years of age
- Antiretroviral treatment-naïve; defined as no current or previous exposure to > 1 week of an antiretroviral drug
Plasma HIV-1 RNA > or = to 1000 copies/mL
- CD4 T-cell count > 200 cells/mm3

E.4

Principal exclusion criteria

- Resistance or partial resistance to any study drug determined by tests at Screening
- Current or historical genotypic and/or phenotypic drug resistance testing showing certain resistance mutations to EFV, TDF, FTC, Protease Inhibitors, (Please see protocol for further information on these exclusionary mutations)
- Chronic HBV/HCV
- Blood tests that inidcate normal liver function (see protocol)
- Hemoglobin < 8.0 g/dL and Platelets < 50,000 cells/mm3

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is the proportion of subjects with plasma HIV-1 RNA < 40 c/mL at Week 24. This will be conducted as a sensitivity
analysis that compliments the snapshot analysis. This uses the last on treatment plasma HIV-1 RNA measurement within an FDA-specified visit window to determine response.

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 24

E.5.2

Secondary end point(s)

1- The antiviral efficacy will be determined by the proportion of subjects with plasma HIV-1 RNA < 40 c/mL at Weeks 48 and 96 using a
sensitivity analysis that compliments the snapshot analysis.
2- The antiviral efficacy will also be assessed by the proportion of subjects with plasma HIV-1 RNA < 200 c/mL at Weeks 24, 48, and 96
using the FDA snapshot algorithm approach with positive response
defined as HIV-1 RNA < 200 c/mL
3- The emergence of HIV drug resistance among samples selected for drug resistance testing will be assessed using the most recent version of the IAS-USA list of HIV-1 drug resistance mutations
4- Changes from baseline in log10 HIV-1 RNA and in CD4+ T-cell counts, and changes in the percentage of CD4+ T-cells over time will be
assessed using on-treatment laboratory results and pre-specified visit windows
5- The frequency of SAEs and AEs leading to discontinuation (DC) will be tabulated directly from the case report forms (CRFs). The summary will count the number of subjects that have at least one event
6- The occurrence of new AIDS defining events (CDC Class C events) will be tabulated from the CRFs. The summary will count the number of subjects that have at least one event
7- The steady-state plasma PK of BMS-955176 will be assessed using the intensive PK data, collected at Week 2 from a subset of subjects

E.5.2.1

Timepoint(s) of evaluation of this end point

1. at Weeks 48 and 96
2. at Weeks 24, 48 and 96
3. at Weeks 24, 48 and 96
4. at Weeks 24, 48 and 96
5. at Weeks 24, 48 and 96
6. at Weeks 24, 48 and 96
7. at Week 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

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

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)

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)

Yes

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

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

Argentina

Canada

Chile

Mexico

South Africa

Thailand

United States

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

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

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:

278

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

150

F.4.2.2

In the whole clinical trial

300

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)

At the conclusion of the study, subjects who continue to demonstrate clinical benefit will be eligible to receive BMS supplied study drug. Study drug will be provided via an extension of the study, a rollover study requiring approval by responsible HA and EC or through another mechanism at the discretion of BMS. BMS reserves the right to terminate access to BMS supplied study drug in the situations listed in section 3.2 of the protocol.

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

2015-06-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-05-22

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2016-11-30

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