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    The EU Clinical Trials Register currently displays   43871   clinical trials with a EudraCT protocol, of which   7290   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Summary
    EudraCT Number:2022-001677-31
    Sponsor's Protocol Code Number:AMB-001
    National Competent Authority:Denmark - DHMA
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2022-10-28
    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
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedDenmark - DHMA
    A.2EudraCT number2022-001677-31
    A.3Full title of the trial
    Administration of the BCL-2 antagonist, venetoclax, to promote apoptosis of HIV-infected cells and reduce the size of the HIV reservoir: An investigator-initiated phase I/IIb clinical trial in people living with HIV on antiretroviral therapy
    (The AMBER Study)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Promoting cell death of HIV-infected cells and reducing the size of the HIV reservoir: An investigator-initiated phase I/IIb clinical trial in people living with HIV on antiretroviral therapy
    (The AMBER Study)
    A.3.2Name or abbreviated title of the trial where available
    AMBER
    A.4.1Sponsor's protocol code numberAMB-001
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorAarhus University Hospital
    B.1.3.4CountryDenmark
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportThe Independent Research Fund Denmark
    B.4.2CountryDenmark
    B.4.1Name of organisation providing supportVilhelm Pedersen og Hustrus Mindelegat
    B.4.2CountryDenmark
    B.4.1Name of organisation providing supportThe Melbourne HIV Cure Consortium
    B.4.2CountryAustralia
    B.4.1Name of organisation providing supportThe Australian National Health and Medical Research Council (NHMRC)
    B.4.2CountryAustralia
    B.4.1Name of organisation providing supportWalter and Eliza Hall Institute of Medical Research
    B.4.2CountryAustralia
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAarhus University Hospital
    B.5.2Functional name of contact pointDanish Inclusion Site
    B.5.3 Address:
    B.5.3.1Street AddressPalle Juul-Jensens Boulevard 99
    B.5.3.2Town/ cityAarhus N
    B.5.3.3Post code8200
    B.5.3.4CountryDenmark
    B.5.6E-mailjesdam@rm.dk
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Venetoclax
    D.2.1.1.2Name of the Marketing Authorisation holderAbbvie
    D.2.1.2Country which granted the Marketing AuthorisationDenmark
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNVenetoclax
    D.3.9.1CAS number 1257044-40-8
    D.3.9.2Current sponsor codeAMB-001
    D.3.9.3Other descriptive nameAMBER
    D.3.9.4EV Substance CodeSUB176260
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboTablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    HIV-1 infection
    E.1.1.1Medical condition in easily understood language
    HIV-1 infection
    E.1.1.2Therapeutic area Diseases [C] - Immune System Diseases [C20]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level LLT
    E.1.2Classification code 10068341
    E.1.2Term HIV-1 infection
    E.1.2System Organ Class 100000004862
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To determine the safety of venetoclax in PLWH on ART
    E.2.2Secondary objectives of the trial
    To determine the effect of venetoclax on HIV persistence in PLWH on ART
    To determine the effect of venetoclax on proapoptotic pathways in PLWH on ART
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Documented HIV-1 infection
    • Age 18-65 years, both included
    • Receiving combination ART for at least 2 years and being on the same ART regimen for at least 4 weeks at the screening visit
    • HIV-1 plasma RNA <50 copies/mL for >2 years (documented on at least 2 occasions within the 2 years) and <20 copies/mL at screening. Episodes of a single HIV plasma RNA 50-500 copies/mL will not exclude participation if the subsequent HIV plasma RNA was <50 copies/mL
    • CD4+ T cell count >500 cells/L at screening and at least two CD4+ T cell counts >500 cells/L in the 24 months prior to screening
    • Ability and willingness to provide informed consent and to continue ART throughout the study
    • For potential study participants who anticipate receiving a SARS-CoV-2 vaccine within the study period, enrolment and commencement of study therapy will be postponed until 4 weeks after completing SARS-CoV-2 vaccination, whereas screening procedures can be initiated before or concurrently with SARS-CoV-2 vaccination.
    • A female, may be eligible to enter and participate in the study if she:
    o Is of non-child-bearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and ≥ 45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy or,
    o Is of child-bearing potential with a negative pregnancy test at both Screening and Day 1 and agrees to use one of the following methods of contraception to avoid pregnancy:
     Complete abstinence from penile-vaginal intercourse from 2 weeks prior to administration of IP, throughout the study, and for at least 2 weeks after discontinuation of all study medications
     Double barrier method (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide)
     Any intrauterine device (IUD) with published data showing that the expected failure rate is <1% per year
     Male partner sterilization confirmed prior to the female subject’s entry into the study, and this male is the sole partner for that subject
     Approved hormonal contraception (Where other medications to be used in the study (e.g., efavirenz and darunavir) are known, or are likely, to significantly interact with systemic contraceptives, resulting in decreased efficacy of the contraceptive, then alternative methods of non-hormonal contraception are recommended)
     Any other method with published data showing that the expected failure rate is <1% per year
     Any contraception method must be used consistently, in accordance with the approved product label and for at least 2 weeks after discontinuation of study therapy.
    • All participants must agree not to participate in a conception process (e.g. active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization, egg donation) during the study
    • Heterosexually active male if they are
    o willing to use an effective method of contraception (anatomical sterility in self that is confirmed prior to study entry) or
    o agree on the use of an effective method of contraception with an effective failure rate of < 1% by his partner (hormonal contraception, intra-uterine device (IUD), or anatomical sterility) from the day of the first vaccination until 7 months after the last vaccination.
    E.4Principal exclusion criteria
    An individual who meets any of the following criteria will be excluded from participation in this study. Study participants receiving cobicistat or a protease inhibitor may opt to switch their ART regimen away from those drugs to allow study participation if this is deemed reasonable by their treating physician but will need to maintain their new regimen for at least 4 weeks prior to enrolling in the study.
    • Current or previous use of a BCL-2 antagonist or other pro-apoptotic agent used as cancer therapy
    • Any concomitant disease where venetoclax treatment is indicated
    • Current use of any strong CYP3A4 inhibitors (such as ketoconazole, voriconazole, posaconazole, itraconazole, ritonavir, cobicistat and clarithromycin)
    • Current use of any HIV protease inhibitor (due to CYP3A4 inhibition)
    • Current use of any strong inhibitor of the P-gp drug efflux pump (this includes cobicistat, ritonavir, azithromycin and clarithromycin)
    o current use of drugs that are P-gp substrates (such as TDF, TAF and dolutegravir) is allowed but will require venetoclax dosing at least 6 hours after intake of those drugs
    o for study participants receiving TDF or TAF we will perform enhanced renal monitoring by quantifying estimated glomerular filtration rate (eGFR) at each study visit during venetoclax administration
    • Current use of strong CYP3A4 inducers (such as carbamazepine, phenytoin, rifampicin and St. John’s wort); moderate CYP3A4 inducers (such as bosentan, efavirenz, etravirine, modafinil and nafcillin) may be used but should be avoided as much as possible
    • Receipt of immunomodulating agents (excluding immunisation) or systemic chemotherapeutic agents within 28 days prior to study entry
    • Any other current or prior therapy which, in the opinion of the investigators, would make the individual unsuitable for the study or influence the results of the study
    • Known hypersensitivity to the components of venetoclax or its analogues
    • Any significant acute medical illness in the past 4 weeks
    • Any evidence of an active AIDS-defining opportunistic infection
    • Individuals who intend to modify their ART regimen within the study period
    • Current or recent gastrointestinal disease or gastrointestinal surgery that may impact the absorption of the investigational drug
    • Active alcohol or substance use that, in the Investigator's opinion, will prevent adequate compliance with study therapy or procedures
    • Unable or unwilling to adhere to protocol procedures
    • History of malignancy or transplantation, excluding adequately treated basal cell carcinoma
    • Co-infection with hepatitis B or C (Individuals with prior hepatitis C infection that is now cleared are eligible for enrolment)
    • Impaired liver function with AST or ALT >3 times upper limit of normal
    • Severe hepatic impairment (Class C) as determined by Child-Pugh classification
    • Impaired renal function with estimated creatinine clearance (eGFR) <50 mL/min
    • Significant cardiac dysfunction
    • Currently pregnant, breastfeeding or unwilling to use barrier contraception
    • Women who are pregnant or breastfeeding or Women of Child Bearing Potential (WOCBP) who are unwilling or unable to use an acceptable method of contraception to avoid pregnancy as specified in the inclusion criteria
    • The following laboratory values at screening (lab tests may be repeated, as clinically indicated, to obtain acceptable values before failure at screening is concluded but supportive therapies are not to be administered within the week prior to screening tests)
    o Hepatic transaminases (AST or ALT) ≥3 x upper limit of normal (ULN)
    o eGFR <50 mL/min
    o Platelet count ≤100 x109/L
    o Absolute neutrophil count ≤1.5x109/L
    o Haemoglobin <10,0 g/dL
    o Total lymphocyte count <800 cells/L
    o CD4+ T cell count <500 cells/L
    E.5 End points
    E.5.1Primary end point(s)
    • Safety defined as treatment-emerging adverse events (AEs) grade 3 (as cited as dose limiting toxicities section 4.2) probably or definitely related to study treatment
    • Safety defined as all other treatment-emerging AEs, graded according to severity and assessed as either not related or possibly, probably or definitely related to study treatment
    E.5.1.1Timepoint(s) of evaluation of this end point
    2Q2025
    E.5.2Secondary end point(s)
    • The frequency of peripheral blood CD4+ T cells containing total and intact HIV-DNA using real-time PCR and the Intact Proviral DNA Assay (IPDA)
    • The proportion of cells containing constitutive and inducible cell-associated multiply spliced HIV RNA (MS HIV-RNA) using the tat/rev induced limiting dilution assay (TILDA)
    • The level of cell-associated unspliced HIV RNA (CA-US HIV RNA) in peripheral blood CD4+ T cells using real-time PCR
    • Numbers and proportions of B cells, total lymphocytes, CD8+ T cells and CD4+ T cells including memory subsets
    • Plasma levels of venetoclax
    • The maximal tolerated dose of venetoclax as determined in the dose-escalation cohorts A-C
    E.5.2.1Timepoint(s) of evaluation of this end point
    2Q2025
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy No
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    Dose-escalation (cohorts A-C) and expansion cohort (cohort D) with 2 arms (staggered dose start)
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    Dose-escalation (cohorts A-C) and expansion cohort (cohort D) with 2 arms (staggered dose start)
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA1
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    Denmark
    E.8.7Trial 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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months2
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months2
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 27
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state27
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 27
    F.4.2.2In the whole clinical trial 27
    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
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2022-10-28
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2022-07-20
    P. End of Trial
    P.End of Trial StatusOngoing
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