Clinical Trials Register

Summary
EudraCT Number:	2010-022413-26
Sponsor's Protocol Code Number:	IDEAL-Study
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2011-04-20
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

Germany - BfArM

A.2

EudraCT number

2010-022413-26

A.3

Full title of the trial

Immediate versus deferred antiretroviral therapy in HIV-infected patients presenting with acute AIDS-defining events (IDEAL-Study)

A.3.1

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

Immediate versus deferred anti-HIV-therapy in patients presenting acute AIDS-defining events.

A.4.1

Sponsor's protocol code number

IDEAL-Study

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	University Medical Center Hamburg-Eppendorf
B.1.3.4	Country	Germany
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	University Medical Center Hamburg-Eppendorf
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	CTC North GmbH & Co. KG
B.5.2	Functional name of contact point	Dr. Silke Schrum
B.5.3	Address:
B.5.3.1	Street Address	Martinistrasse 64
B.5.3.2	Town/ city	Hamburg
B.5.3.3	Post code	20251
B.5.3.4	Country	Germany
B.5.4	Telephone number	+4940524719210
B.5.5	Fax number	+4940524719129
B.5.6	E-mail	s.schrum@ctc-north.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	Reyataz® 300mg-Hartkapseln
D.2.1.1.2	Name of the Marketing Authorisation holder	Bristol-Myers Squibb
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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.3.4	Pharmaceutical form	Capsule, hard
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	ATAZANAVIR
D.3.9.1	CAS number	198904-31-3
D.3.9.4	EV Substance Code	SUB16398MIG
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	300
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	Yes
D.2.1.1.1	Trade name	Norvir® 100mg-Filmtabletten
D.2.1.1.2	Name of the Marketing Authorisation holder	Abbott
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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.3.4	Pharmaceutical form	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	RITONAVIR
D.3.9.1	CAS number	155213-67-5
D.3.9.4	EV Substance Code	SUB10342MIG
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	100
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Patients in late stage of HIV-infection, treatment naive or without ART for the last 6 month with an acute AIDS-defining illness, namely PCP or TE.

E.1.1.1

Medical condition in easily understood language

HIV-infected and treatment naive patients or without ART treatment for the last 6 month suffering from acute AIDS-defining illness, namely special kind of pneumonia or encephalitis.

E.1.1.2

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutic techniques [E02]

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	10001509
E.1.2	Term	AIDS
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 compare the rates of clinical progression between both groups. Progression is defined as death, all new/relapsing opportunistic infections (OI), and other grade 4 clinical endpoints (evaluated by standardized toxicity tables) within 24 weeks after randomization.

E.2.2

Secondary objectives of the trial

•to evaluate and to compare hospitalization days after completion of initial OI treatment between both groups.
•to evaluate the incidence of immune reconstitution inflammatory syndrome (IRIS, definition see Objectives) in both groups during the first 24 weeks.
•to evaluate and to compare the virological outcome proportion in both groups. Virological outcome is assessed by HIV-1 plasma viral load at Week 24 (proportion of patients achieving HIV RNA < 400/<50 copies/mL). For definition of virological failure, see below.
•to evaluate and to compare the frequency changes in ART regimen for lack of efficacy or of toxicity in both groups.
•to evaluate the quality of life (QOL) and the adherence to the ARV regimen in subjects starting tenofovir, emtricitabine and atazanavir/ritonavir at late stages of HIV-1-infection.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

•No prior antiretroviral therapy for at least 6 month and an acute AIDS defining event, namely PCP or TE.

•Naïve to antiretroviral therapy. No prior antiretroviral therapy for at least 6 month (patients without evidence for prior virological failure and without evidence of resistance mutation against the planned ART therapy may be allowed)and an and an

•Acute AIDS defining event, namely PCP or TE. Prior ART for mother to child transmission (MTCT) prophylaxis is allowed.

•Ability to take oral medications

•>= 18 years old

•Adequate renal function by calculated creatinine clearance < 60 mL/min according to the Cockcroft–Gault formula.

•Negative serum pregnancy test (females of childbearing potential only i.e., not surgically sterile or at least 2 years post-menopausal).

•Women of childbearing potential (WOCBP) must be using a highly effective method of contraception to avoid pregnancy throughout the study and for up to 30 days after the last dose of study drugs in such a manner that the risk of pregnancy is minimized – refer to Section x for the definition of highly effective method of birth control.

•Male subjects who are heterosexually active must be willing to use effective barrier contraception (e.g. condom with spermicide) from screening through completion of the study and continuing for up to 30 days after the last dose of study drugs

•The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures. In the case the patient is not able to give informed consent his legal representative has to give informed consent for the patient. This can be done after the incompetence of given consent was confirmed by a psychiatric specialist.

E.4

Principal exclusion criteria

•Pregnant or lactating subjects

•Prior antiretroviral treatment for the last six month

•Known hypersensitivity to atazanavir/ritonavir

•Documented resistance to any of the study drugs (either genotypic or phenotypic)

•Severe hepatic impairment

•Hepatic transaminases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) >/= 5 x upper limit of normal (ULN)

•Subjects receiving ongoing therapy with any of the medications that are contraindicated with any of the study drugs. Administration of any of these medications must be discontinued at least 14 days prior to the Baseline visit and for the duration of the study period. The full list of disallowed medications can be found in Appendix IV.

•Other AIDS-defining events (see Appendix VIII for definition of AIDS-defining events) than PCP or TE present at screening, except for oesophageal candidiasis and Kaposi sarcoma (KS) not requiring systemic chemotherapy.

•Prior history of significant renal disease

•Any current known clinical or symptomatic laboratory parameter of Grade 4 (see Appendix ). Asymptomatic Grade 4 abnormalities will be permitted at the discretion of the investigator if deemed clinically appropriate (excluding adverse events and laboratory parameters mentioned elsewhere in the inclusion/exclusion criteria). Abnormalities deemed insignificant by the investigator must be discussed with the Medical Monitor prior to enrollment.

•Malignancies requiring any systemic therapy within 30 days of baseline

•Current alcohol or substance use judged by the investigator to potentially interfere with subject study compliance

•Subjects currently taking part in any other clinical trial using an investigational product, with the exception of studies where the treatment studied has been stopped for more than 1 month prior to baseline

•Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for the study or unable to comply with the dosing requirements

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is clinical progression including death, all new or relapsing OI, and other G4 clinical endpoint within 24 weeks. For G4 events standardized toxicity grading tables will be used (http://www.ucdmc.ucdavis.edu/clinicaltrials/documents/vaccine_toxicity _grading _table.pdf). For abnormalities not found in the Toxicity Tables, a Grade 4 event will be defined as potentially life-threatening (extreme limitation in activity, significant assistance required; significant medical intervention/therapy required, hospitalization or hospice care probable). Patients who drop out of study observation before end of week 12 are counted as clinical progression.

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline, week 4, 8, 12, 16, 20, 24

E.5.2

Secondary end point(s)

•Hospitalization days after completion of OI treatment

•Incidence of immune reconstitution inflammatory syndrome (IRIS) as judged by the site investigator compared in the two groups during the first 24 weeks.

•Virological outcome at week 24 (proportion of patients achieving HIV RNA < 400 (<50 copies/mL).

•Immunological outcome at week 24 (CD4 T-cell counts and change from baseline at week 24 (absolute, relative, CD4/CD8 ratio)

•Proportion of patients with changes in ARV regimen for lack of efficacy or of toxicity

•Quality of life (QOL), including overall self-reported QOL at Week 24

E.5.2.1

Timepoint(s) of evaluation of this end point

Baseline, week 4, 8, 12, 16, 20, 24 with a main focus on week 24

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

E.6.5

Efficacy

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

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)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

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

Information not present in EudraCT

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

Yes

E.8.2.3.1

Comparator description

early versus deferred treatment

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

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

last patient last phone contact

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

F. Population of Trial Subjects
F.1 Age Range
F.1.1	Trial has subjects under 18	No
F.1.1.1	In Utero	Information not present in EudraCT
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	Information not present in EudraCT
F.1.1.3	Newborns (0-27 days)	Information not present in EudraCT
F.1.1.4	Infants and toddlers (28 days-23 months)	Information not present in EudraCT
F.1.1.5	Children (2-11years)	Information not present in EudraCT
F.1.1.6	Adolescents (12-17 years)	Information not present in EudraCT
F.1.2	Adults (18-64 years)	Yes
F.1.2.1	Number of subjects for this age range:	170
F.1.3	Elderly (>=65 years)	Yes
F.1.3.1	Number of subjects for this age range:	40
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	210

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

2011-05-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-07-29

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2015-04-28

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