The Late Presenter Treatment Optimisation Study (LAPTOP)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

NEAT ID Foundation

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

5 Aug 2019 → 17 Jun 2024

Decision date (initial)

2023-11-06

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Janssen Pharmaceutica NV · Giliead Sciences Inc

External identifiers

EU CT number

2023-505167-36-00

EudraCT number

2018-003481-13

ClinicalTrials.gov

NCT03696160

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To demonstrate an Integrase Inhibitor containing regimen is no better than a boosted Protease Inhibitor regimen in patients with advanced HIV infection. If the integrase inhibitor regimen is proved to be no better then, we would like to demonstrate whether the Integrase inhibitor regime is superior to the Protease Inhibitor containing regimen.

Secondary objectives 2

1. 1. To investigate the incidence of the following clinical events; immunological and virological response, tolerability, resistance development, discontinuation of therapy due to tolerability, quality of life and Immune Reconstitution Inflammatory Syndrome (IRIS).
2. 2. To assess whether virological response is better predicted by next generation deep sequencing rather than the standard population sequencing currently performed.

Conditions and MedDRA coding

Patients who present late on during their acquisition of the HIV-1 (Human Immunodeficiency Virus)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Ability to understand and sign a written informed consent form (ICF) and must be willing to comply with all study requirements
2. ≥ 18 years
3. HIV-1 infected AIDS except active tuberculosis (TB) or cryptococcal meningitis with any CD4 cell count, or; severe bacterial infection (BI) and must have a CD4 cell count < 200/μL within 28 days prior to study entry, or; any symptoms or no symptoms with CD4 cell count < 100/μL within 28 days prior to study entry and must have an entry HIV viral load > 1000 copies/mL, or; currently being treated for opportunistic infections (OI)
4. Have an entry HIV viral load > 1000 copies/mL
5. Able to take oral medications
6. ART-naïve prior to study enrolment
7. Willing to use acceptable methods of contraception

Exclusion criteria 12

1. Any therapeutic ARV which commenced less than 2 weeks prior to screening and which was taken for more than 48 hours
2. Systemic cancer chemotherapy within 30 days prior to study entry, or current treatment for cancer (with the exception of Kaposi’s sarcoma) or lymphoma.
3. Current or anticipated use of contraindicated medications (see Summary of Product Characteristics (SmPC) for Symtuza® and Biktarvy®) or anticipated systemic chemotherapy during study enrolment (administration of any contraindicated medication must be discontinued at least 30 days prior to the baseline visit and for the duration of the study).
4. Known resistance to the components of study medications
5. History or symptoms of advanced renal and/or hepatic impairment. Such as, kidney failure requiring dialysis; eGFR <30 mL/min; hepatic transaminases (AST and ALT) > 5 x upper limit of normal (ULN); or, platelet count <50,000.
6. Current drug or alcohol use that, in the opinion of the Investigator, would cause interference with the study.
7. Cryptococcal meningitis or active TB, or current or expected treatment requiring Rifampicin or Rifabutin (patients with expected latent TB will have a TB test (IGRAs e.g. ELISPOT, QuantiFERON etc.) at their screening visit).
8. History or presence of allergy to the study drugs or their components, or drugs of their class.
9. Using any concomitant therapy disallowed as per the product labelling for the study drugs.
10. Any investigational drug within 30 days prior to the study drug administration.
11. Patients with severe (Child Pugh class C) hepatic impairment.
12. Women who are pregnant, breastfeeding or plan to become pregnant or breastfeed during the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Time to failure, as the first occurrence of specified virological or clinical reasons.

Secondary endpoints 12

1. Proportion of patients with HIV-RNA viral load < 50 copies/mL at week 24, 36, 48
2. HIV-1 drug resistance at confirmed virological failure (genotype)
3. Time to reach CD4 count > 200/μL (first measurement)
4. Proportion of patients with CD4 cell count < 200 μL and < 350μL at week 4, 8, 12, 24, 36, 48
5. CD4/CD8 ratio at week 4, 8, 12, 24, 36, 48
6. Incidence of IRIS in the two arms through week 48
7. Incidence and duration of hospitalisation, rate of relapse of specific OI/BI through week 48
8. Safety and tolerability, measured by Grade 2, 3 and 4 signs and symptoms and laboratory toxicities through week 48
9. ART and OI/BI treatment changes and dose modifications due to toxicities and DDI with ART, and IRIS through week 48
10. Health care resource use, including total inpatient days and emergency room visits through week 48
11. QOL and functional status outcomes, including overall self-reported QOL and functional status compared in the two groups at week 48
12. Discontinuation or modification of study medication due to insufficient virological response, resistance mutations at baseline, or resistance mutation development before week 48

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

NEAT ID Foundation

Sponsor organisation

NEAT ID Foundation

Address

Hoogstraat 322, Pl 709 Pl 709

City

Brussels

Postcode

1000

Country

Belgium

Scientific contact point

Organisation

NEAT ID Foundation

Contact name

Project Manager

Public contact point

Organisation

NEAT ID Foundation

Contact name

Project Manager

Locations

6 EU/EEA countries · 39 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 2 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications