Clinical Trials Register

Summary
EudraCT Number:	2011-004693-29
Sponsor's Protocol Code Number:	IFNHIV
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2012-03-02
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2011-004693-29

A.3

Full title of the trial

Pegylated interferon alfa-2a USE FOR CONTROLLING virological rebound after suspension of antiretroviral treatment IN PATIENTS WITH CHRONIC HIV INFECTION

USO DELL’INTERFERONE ALFA-2A PEGHILATO PER CONTROLLARE IL REBOUND VIROLOGICO DOPO SOSPENSIONE DEL TRATTAMENTO ANTORETROVIRALE IN PAZIENTI CON INFEZIONE DA HIV CRONICA

A.3.1

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

use of interferon to control the virological rise after discontinuation of antiretroviral treatment in patients with chronic HIV

uso di interferone per controllare il rialzo virologico dopo sospensione del trattamento antiretrovirale in pazienti con infezione da HIV

A.3.2

Name or abbreviated title of the trial where available

IFNHIV

A.4.1

Sponsor's protocol code number

IFNHIV

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	ISTITUTO NAZIONALE DELLE MALATTIE INFETTIVE LAZZARO SPALLANZANI
B.1.3.4	Country	Italy
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	ISS
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	INMI Lazzaro Spallanzani
B.5.2	Functional name of contact point	DIpartimento Clinico
B.5.3	Address:
B.5.3.1	Street Address	Via Portuense 292
B.5.3.2	Town/ city	Roma
B.5.3.3	Post code	00149
B.5.3.4	Country	Italy
B.5.4	Telephone number	0655170360
B.5.5	Fax number	0655170407
B.5.6	E-mail	gianpiero.doffizi@inmi.it

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	PEGASYS*SC 1FL 180MCG/1ML
D.2.1.1.2	Name of the Marketing Authorisation holder	ROCHE SpA
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	NA
D.3.9.1	CAS number	NA
D.3.9.2	Current sponsor code	IFNHIV
D.3.9.3	Other descriptive name	NA
D.3.9.4	EV Substance Code	NA
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	180
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	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

HIV-1 infected patients

Pazienti con infezione cronica da HIV-1

E.1.1.1

Medical condition in easily understood language

HIV infected patients

Pazienti affetti da HIV

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10020161
E.1.2	Term	HIV infection
E.1.2	System Organ Class	10021881 - Infections and infestations

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 effectiveness of 'pegylated interferon alfa-2a (180 μg) once a week as a simplification of HAART, to keep the HIV viral load suppressed when started 1 week before the suspension of HAART in patients with stably suppressed viremia (HIV RNA <40 copies / mL)

Comparare l’efficacia dell’ interferone alfa-2a peghilato (180 μg) una volta la settimana come semplificazione della HAART, per mantenere la carica virale di HIV soppressa quando iniziato 1 settimana prima della sospensione della HAART in pazienti con viremia stabilmente soppressa (HIV RNA <40 copie/mL).

E.2.2

Secondary objectives of the trial

- evaluation of toxicity and tollerability of peg-IFN alpha-2a - evaluate if peg-IFN alpha-2a is able to decrease CD4+ latently infected cells - to evaluate the effect of peg-IFN alpha-2a on the innate and specific immunitary response

verranno inoltre analizzati: - Valutazione della tossicità e tollerabilità dell’interferone alfa-2a peghilato - se l’interferone alfa-2a peghilato è capace di diminuire il numero delle cellule CD4+ latentemente infette da HIV - l’effetto dell’ interferone alfa-2a peghilato sulla risposta immunitaria innata e specifica

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Will be enrolled only patients who require interruption of HAART for toxicity or who spontaneously decide to suspend the anti-HIV therapy. • Patients male and female with age between 18 and 65 years. • Aware of providing informed consent • Patients with HIV infection with ELISA and Western Blot documented, with a stable viral load suppressed by at least 18 months in the course of antiretroviral treatment effective. • HIV RNA <40 copies / mL and CD4> 500 cells / mL (nadir ≥ 250 cells / mL) conscription • HIV RNA> 10,000 copies / mL before the antiretroviral treatment • For female patients negative pregnancy test (Beta HCG) and use of effective contraception during the study • Karnofsky score ≥ 80% • Adherence to treatment regimen and the planned study • Abstention from the use of immunomodulatory drugs during the study • Thyroid function in the norm

• Verranno arruolati esclusivamente pazienti che richiedono l’interruzione della HAART per tossicità o che spontaneamente decidono di sospendere la terapia anti HIV. • Pazienti di sesso maschile e femminile con età compresa tra i 18 e 65 anni. • Consapevoli di fornire un consenso informato • Pazienti con infezione da HIV con test ELISA e Western Blot documentato, con carica virale stabilmente soppressa da almeno 18 mesi in corso di trattamento antiretrovirale efficace. • HIV RNA < 40 copie/mL e CD4+ > 500 cellule/mL (nadir ≥ 250 cellule/mL) all’arruolamento • HIV RNA > 10.000 copie/mL prima del trattamento antiretrovirale • Per pazienti di sesso femminile test di gravidanza negativo (Beta HCG) e uso di metodi contraccettivi efficaci durante lo studio • Karnofsky score ≥ 80% • Astensione dall’uso di farmaci immunomodulatori durante lo studio • Funzione tiroidea nella norma

E.4

Principal exclusion criteria

• Pregnancy in place and / or breastfeeding • CD4 + cell counts <500 cells or nadir CD4 <250 cells / mL. • History of immune-modulating therapies for over 2 weeks during the 6 months prior to enrollment as interferons, corticosteroids, cancer chemotherapy, cyclosporine, tacrolimus, OKT3, interleukins (IL2, IL7), cyclophosphamide, methotrexate, immunoglobulins, G/M- CSF hydroxyurea, thalidomide, pentoxifylline, timopentina, thymosin • Other concurrent medical conditions, anemia (Hgb <9.1), neutropenia (<1000), thrombocytopenia (platelets <50,000), citonecrosi liver (AST / ALT x5), renal insufficiency (creatinine> x2), drug addiction, alcohol abuse, uncontrolled diabetes mellitus • History of heart disease • History of depression and / or severe psychiatric disorders • Chronic hepatitis HBV co • History of autoimmune disorders including: Crohn's disease, ulcerative colitis the rectum, psoriasis, rheumatoid arthritis, myositis • History of trapaianto • Hypersensitivity to interferon

• Gravidanza in atto e/o allattamento materno • Conta delle cellule CD4+ < 500 cellule o nadir CD4+ <250 cellule/mL. • Storia di terapie immuno-modulanti per oltre 2 settimane durante i 6 mesi antecedenti all’arruolamento • anemia (Hgb <9,1) • neutropenia (<1000) • trombocitopenia (piastrine < 50.000) • Tossicodipendenza • abuso alcolico • diabete mellito non controllato • Storia di malattie cardiache • Storia di depressione e/o gravi disturbi psichiatrici • Epilessia e/o compromissione della funzionalità del sistema nervoso centrale • Malattia tiroidea preesistente non controllabile con terapia convenzionale • Grave disfunzione epatica(AST/ALT x5) e renale (creatinina > x2) • Epatite cronica con cirrosi avanzata e scompenso epatico • Epatite cronica da HBV concomitante • Storia di malattie autoimmuni inclusa: malattia di Chron, retto colite ulcerosa, psoriasi, artrite reumatoide, miosite • Storia di trapianto • Ipersensibilità all’interferone

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is the percentage of patients with viral load <400 copies / mL at the end of 12 weeks of discontinuation of HAART

L’endpoint primario dello studio è costituito dalla percentuale di pazienti con carica virale < 400 copie/mL alla fine delle 12 settimane di sospensione della HAART

E.5.1.1

Timepoint(s) of evaluation of this end point

12 weeks

12 settimane

E.5.2

Secondary end point(s)

• Adverse events and side effects • Phenotype of maturation and differentiation phenotype of CD4, CD8, NK, pDC, MDC, Treg and gamma / delta flow cytometry • Analysis of specific CD8 immune response against HIV antigens • NKR phenotype and cytotoxic activity against NK target cells for in vitro flow cytometry • Activities of the PCA MDC to recall antigen and HIV antigens by flow cytometry and ELISPOT • loads of HIV proviral DNA in PBMC and plasma HIV RNA zero time, 2 weeks, 4 weeks, 8 weeks and 12 weeks

•Eventi avversi e effetti collaterali •Fenotipo di maturazione e differenziamento del fenotipo delle cellule CD4, CD8, NK, pDC, mDC, Treg e gamma/delta in citometria a flusso •Analisi della risposta immunitaria CD8 specifica contro antigeni di HIV •Fenotipo NKR e l’attività citotossica contro cellule bersaglio per NK in vitro in citometria a flusso •Attività delle APC mDC ad antigeni di richiamo ed antigeni di HIV in citometria a flusso ed EliSpot •carica provirale di HIV DNA in PBMC e HIV RNA plasmatico a tempo zero, 2 settimane, 4 settimane, 8 settimane e alla 12a settimana.

E.5.2.1

Timepoint(s) of evaluation of this end point

- 12 weeks - Loads of HIV proviral DNA in PBMC and plasma HIV RNA at time zero, 2 weeks, 4 weeks, 8 weeks and 12 weeks

- 12 settimane - carica provirale di HIV DNA in PBMC e HIV RNA plasmatico a tempo zero, 2 weeks, 4 weeks, 8 weeks and 12 weeks

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

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

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

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

il gruppo di controllo non assumerà il farmaco

The control group did not take this medicine

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

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

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

F.1.1

Number of subjects for this age range:

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:

F.1.3

Elderly (>=65 years)

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

F.4.2.2

In the whole clinical trial

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)

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

2011-11-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-11-15

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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