Clinical Trials Register

Summary
EudraCT Number:	2015-005238-23
Sponsor's Protocol Code Number:	MCA-896
National Competent Authority:	Denmark - DHMA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2016-08-03
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

Denmark - DHMA

A.2

EudraCT number

2015-005238-23

A.3

Full title of the trial

A phase 2a, randomized study of the combination of romidepsin and 3BNC117 to evaluate the effects on the HIV-1 reservoir (ROADMAP)

A.3.1

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

The effect of anti-latency reversing therapy and broadly neutralizing antibodies on the HIV-1 reservoir in patients on antiretroviral therapy - a randomized trial (ROADMAP)

Effekten af et latensreverterende lægemiddel og neutraliserende antistoffer på HIV-1 reservoiret blandt personer i antiretroviral behandling – et randomiseret studie (ROADMAP)

A.3.2

Name or abbreviated title of the trial where available

ROADMAP

A.4.1

Sponsor's protocol code number

MCA-896

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	Rockefeller University
B.1.3.4	Country
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	amfAR
B.4.2	Country
B.4.1	Name of organisation providing support	Bill and Melinda Gates Foundation
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Dept. of Infectious Diseases
B.5.2	Functional name of contact point	Ole Søgaard
B.5.3	Address:
B.5.3.1	Street Address	Palle Juul-Jensens Boulevard 99
B.5.3.2	Town/ city	Aarhus
B.5.3.3	Post code	8200
B.5.6	E-mail	olesoega@rm.dk

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	Istodax
D.2.1.1.2	Name of the Marketing Authorisation holder	Celgene Corporation
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	Romidepsin
D.3.4	Pharmaceutical form	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	ROMIDEPSIN
D.3.9.2	Current sponsor code	MCA-0896
D.3.9.3	Other descriptive name	Istodax
D.3.9.4	EV Substance Code	SUB26362
D.3.10	Strength
D.3.10.1	Concentration unit	mg/m2 milligram(s)/square meter
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
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	3BNC117
D.3.4	Pharmaceutical form	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	3BNC117
D.3.9.2	Current sponsor code	MCA-0896
D.3.9.3	Other descriptive name	Roadmap
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	20
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)	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

HIV infection

HIV infektion

E.1.1.1

Medical condition in easily understood language

HIV infection

HIV infektion

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	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10020180
E.1.2	Term	HIV positive
E.1.2	System Organ Class	100000004848

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
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

Evaluate the effects of romidepsin plus 3BNC117 or romidepsin alone on delaying or preventing viral rebound in HIV-1-infected individuals during an analytical interruption of ART.

Vurdere effekten af romidepsin plus 3BNC117 eller romidepsin alene på tiden til genopblussen af virus hos HIV-1 patienter under en monitoreret behandlingspause af HIV behandlingen.

E.2.2

Secondary objectives of the trial

1) Evaluate the safety of romidepsin plus 3BNC117 or romidepsin alone in ART-treated HIV-1 infected individuals
2) Evaluate the effects of romidepsin plus 3BNC117 or romidepsin alone on the size of the replication competent HIV-1 reservoir in ART-treated HIV-1-infected individuals;
3) Evaluate the immunomodulatory effects of romidepsin plus 3BNC117 or romidepsin alone in ART-treated HIV-1-infected individuals.

1) Vurdere sikkerheden af romidepsin plus 3BNC117 eller romidepsin alene hos HIV-1 patienter, som er i HIV-behandling
2) Vurdere effekten af romidepsin plus 3BNC117 eller romidepsin alene på størrelsen af det replikationskompetente reservoir hos HIV-1 patienter, som er i HIV-behandling
3) Vurdere de immunomodulatoriske effekter af romidepsin plus 3BNC117 eller romidepsin alene hos HIV-1 patienter, som er i HIV-behandling

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1) Adults age 18-65 years with documented HIV-1 infection
2) CD4+ T-cell count >500 cells/mm3 at screening
3) On ART for a minimum of 18 months and HIV-1 RNA plasma level of < 50 copies/ml by standard assays for at least 12 months (a single viral load measurement > 50 but < 500 copies/ml during this time period is allowable).
4) Individuals on protease inhibitor or NNRTI-based regimens must be willing to switch to an integrase-inhibitor-based regimen (raltegravir or dolutegravir) prior to enrollment.

1) Alder mellem 18 og 65 år med dokumenteret HIV-1 infektion
2) CD4+ T celletal >500 celler/mm3 ved screening
3) HIV-behandlet i minimum 18 måneder med HIV-1 RNA i blodet <50 kopier/ml for minimum 12 måneder (et enkelt virus-blip >50, men <500 kopier/ml i periosden er tilladt)
4) HIV-1 patienter, som får behandlingsregimen baseret på enten proteasehæmmer eller NNRTI, skal skiftes til et integrasehæmmer-baseret (raltegravir eller dolutegravir) forud for inklusion

E.4

Principal exclusion criteria

1) Use of systemic corticosteroids, immunosuppressive anti-cancer, or other medications considered significant by the investigators within the last 6 months
2) Pregnancy as determined by a positive urine beta-hCG.
3) Participant unwilling to use two reliable contraception methods (i.e. condom with spermicide, diaphragm with spermicide, hormone-eluting IUD, hormone-based contraceptive with condom) for the study duration.
4) Currently breast-feeding.
5) History of resistance to 2 or more classes of antiretroviral medication
6) Any medical, psychiatric, social, or occupational condition that, as judged by the investigators, would interfere with the evaluation of study objectives (such as severe alcohol or drug abuse, dementia).
7) Hepatitis B or C infection as indicated by the presence of Hepatitis B surface antigen (HBsAg) or hepatitis C virus RNA (HCV-RNA) in blood.
8) Receipt of an HDAC inhibitor or 3BNC117 in the past 2 years.
9) Have a history of AIDS-defining illness within 3 years prior to enrollment.
10) History of significant coronary artery disease, myocardial infarction, percutaneous coronary intervention with placement of cardiac stents.
11) ECG at screening that shows QTc >450 msec when calculated using the Fridericia formula from either lead V3 or V4.
12) Use of Coumadin or Coumadin derivatives
13) Laboratory abnormalities in the parameters listed below:
13a) Absolute neutrophil count ≤ 1,300
13b) Hemoglobin ≤ 10 gm/dL
13c) Platelet count ≤ 125,000
13d) ALT ≥ 2.0 x ULN
13e) AST ≥ 2.0 x ULN
13f) Total bilirubin ≥ 2.0 x ULN (for participants on atazanavir, a total bilirubin up to 3 x ULN is allowable)
13g) eGFR < 60 mL/min/1.73m2
14) Any vaccination within 14 days prior to 3BNC117 administration
15) Receipt of any therapeutic HIV vaccine in the past
16) Receipt of any monoclonal antibody therapy of any kind in the past 2 years
17) Participation in another clinical study of an investigational product currently or within past 12 weeks, or expected participation during this study.

1) Brug af immunmodulerende midler eller systemisk kemoterapi indenfor de seneste 6 måneder før inklusion
2) Gravid eller positiv graviditetstest under screening hos kvinder i den fødedygtige alder eller kvinder, der planlægger at blive gravide i forsøgsperioden, som ikke kan/vil benytte sikker antikonception (indeholde ikke-østrogener i henhold til Sundhedsstyrelsens retningslinjer) i hele studieperioden
3) Mænd eller kvinder, som ikke kan/vil bruge barriereprævention (kondom/femidom) i hele studieperioden
4) Ammende kvinde
5) Kendt resistens overfor >2 regimer af HIV behandling
6) Aktuel alkohol- eller stofmisbrug, som Investigator finder ensbetydende med manglende compliance i henhold til forsøgsplanen
7) Hepatitis B or C infektion ved tilstedeværelsen af hepatitis B overflade antigen (HBsAg) eller hepatitis C virus RNA (HCV-RNA) i blodet
8) Tidligere behandlet med: HDACi eller 3BNC117 indenfor de seneste 2 år
9) AIDS-definerende opportunistisk infektion seneste 3 år før screening
10) Medicinsk historie med: Alvorlig hjertesygdom, symptomatisk eller asymptomatisk arytmier, besvimmelsesepisoder, eller øget risiko for Torsades de pointes (ved f.eks. hjertesvigt)
11) Elektrokardiogram ved screening, som viser QTc >450 ms, når beregnet ved Fridericia formula fra enten afledning V3 eller V4
12) Brug af warfarin or warfarin-derivater
13) Laboratoriemæssig forhold ved screening:
13a) Antal neutrofile granolucytter ≤1.3 x109/L
13b) Hæmoglobin ≤ 10 gm/dL
13c) Antal blodplader ≤125 x109/L
13d+e) Leverenzymer (aspartat-aminotransferase eller alanin-aminotransferase) ≥2 x øvre normalgrænse (ULN)
13f) Total bilirubin ≥2 ULN (hvis behandles med atazanavir, da ≥3 ULN)
13g) Estimated glomerular filtration rate (eGFR) ≤60 mL/min (baseret på serum kreatinin eller anden valid markør)
14) Vaccineret indenfor 14 dage i forhold til 3BNC117 infusion
15) Tidligere behandlet med: HIV vaccine
16) Tidligere behandlet med: Monoklonale antistoffer mod HIV indenfor de seneste 2 år
17) Deltaget i andre interventionsstudier indenfor seneste 12 uger fra screening

E.5 End points

E.5.1

Primary end point(s)

Days to viral rebound during analytic treatment interruption or days to reinitiation of ART in participants who restart ART before viral rebound. Viral rebound is defined as HIV-1 RNA ≥ 200 on 2 consecutive measurements during ATI.

E.5.1.1

Timepoint(s) of evaluation of this end point

During analytic treatment interruption.

E.5.2

Secondary end point(s)

1) Safety evaluation, as measured by rate and severity of adverse events (AE), serious adverse events (SAE), and serious unexpected serious adverse reactions (SUSAR)
2) Size of the functional, latent HIV-1 reservoir as determined by the number of infectious units per 106 resting memory CD4+ T cells (IUPM) using a viral outgrowth assay before and after therapy. Post therapy measurements will occur after the second cycle, just before ATI. These measurements will be performed in Dr. Siliciano’s laboratory
3) Size of the proviral HIV-1 reservoir as determined by total HIV-1 DNA and episomal HIV-1 DNA (2-LTR) in circulating total CD4+ T cells.
4) Plasma HIV-1 RNA, as measured by a routine clinical assay (Cobas Taqman; detection limit 20 copies/mL) and a transcription mediated amplification (TMA)-based assay.

E.5.2.1

Timepoint(s) of evaluation of this end point

1) During trial
2) Before and after therapy
4) During trial

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

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

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)

Yes

E.8.2.2

Placebo

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

Denmark

Germany

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.

Sidste besøg sidste deltager

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

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:

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)

None.

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

2016-10-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-04-06

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2019-07-22

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