Impact of Doravirine in Liver Steatosis and Fibrosis in PLWH. A pilot, proof of concept study (DORALI Study)

2023-504952-87-00 Protocol DORALI Therapeutic use (Phase IV) Ongoing, recruitment ended

Start 13 Jan 2025 · Status Ongoing, recruitment ended · 1 EU/EEA countries · 3 sites · Protocol DORALI

Overview

Sponsor-declared trial summary

Phase Therapeutic use (Phase IV)
Status Ongoing, recruitment ended
Participants planned 50
Countries 1
Sites 3

Human Immunodeficiency Virus

Determine changes in liver steatosis measured by CAP (Controlled Attenuation Parameter, expressed in db/m) and liver fibrosis measured by transient elastography (expressed in Kpa) in HIV asymptomatic individuals who present with some degree of confirmed liver steatosis (>=S1-238 a 260 dB/m) or liver fibrosis (>=F2->7Kp…

Key facts

Sponsor
Fundacion Fls De Lucha Contra El Sida Las Enfermedades Infecciosas Y La Promocion De La Salud Y La Ciencia
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Virus Diseases [C02], Diseases [C] - Immune System Diseases [C20]
Trial duration
13 Jan 2025 → ongoing
Decision date (initial)
2024-03-11
Transition trial
No
Low-intervention
Yes
Rare-disease indication
No
Vulnerable population
No
Funding sources
Merck & Co. (Merck Sharp and Dohme)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety

Determine changes in liver steatosis measured by CAP (Controlled Attenuation Parameter, expressed in db/m) and liver fibrosis measured by transient elastography (expressed in Kpa) in HIV asymptomatic individuals who present with some degree of confirmed liver steatosis (>=S1-238 a 260 dB/m) or liver fibrosis (>=F2->7Kpa) who switch to a regimen based in Doravirine. Changes in HIV general outcomes as well as metabolic results will be evaluated at baseline and week 48.

Secondary objectives 2

  1. Determine changes in fat liver content by MRI in a subset of 40 PLWH included in the study who change to a regimen based in Doravirine.
  2. Determine changes in lipoprotein particles at week 48.

Conditions and MedDRA coding

Human Immunodeficiency Virus

Study design 1 period

#TitleAllocationBlindingRoles blindedArms
1 Switch Or Continue
The participate in this study where they will be randomly assigned to one of the three groups.
Randomised Controlled None Control Arm: Bictegravir 50mg / Emtricitabine 200mg / Tenenofovir alafanamide 25 mg Oral Every Day
Experimental Arm One: Doravirine 100 mg Oral Every Day + Emtricitabine / Tenofovir Alafanamide 200/25 mg Oral Every Day
Experimental Arm Two: Doravirine 100 mg / Lamivudine 300 mg / Tenofovir disoproxilo 245 mg Oral Every Day

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

  1. Eligible subjects need to present some degree of liver steatosis (Fibroscan: >=S1-238 a 260 dB/m) or liver fibrosis (>=F2->7Kpa).

Exclusion criteria 1

  1. Any evidence of current or previous Hepatitis B or C [Active Surface Hepatitis B Ag (HBAgS) OR negative HBAgS and negative hepatitis B surface antibody (anti-HBs) with positive anti-core antibody (anti-HBc) and positive HBV DNA. Hepatitis C IgG positive]

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Liver steatosis measured and liver fibrosis measured by CAP (Controlled Attenuation-Parameter, expressed in db/m) and transient elastography respectively

Secondary endpoints 2

  1. Fat liver content by MRI
  2. Lipoprotein particles at week 48

Investigational products

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

Test 3

Delstrigo 100 mg/300 mg/245 mg film-coated tablets

PRD6778264 · Product

Active substance
Lamivudine
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL
Max daily dose
1 U unit(s)
Max total dose
1 U unit(s)
Max treatment duration
48 Week(s)
Authorisation status
Authorised
ATC code
J05AR24 — -
Marketing authorisation
EU/1/18/1333/001
MA holder
MERCK SHARP & DOHME BV
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Pifeltro 100 mg film-coated tablets

PRD6790340 · Product

Active substance
Doravirine
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL
Max daily dose
1 U unit(s)
Max total dose
1 U unit(s)
Max treatment duration
48 Week(s)
Authorisation status
Authorised
ATC code
J05AG06 — -
Marketing authorisation
EU/1/18/1332/001
MA holder
MERCK SHARP & DOHME BV
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Descovy 200 mg/25 mg film-coated tablets

PRD4052394 · Product

Active substance
Emtricitabine
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL
Max daily dose
1 U unit(s)
Max total dose
1 U unit(s)
Max treatment duration
48 Week(s)
Authorisation status
Authorised
ATC code
J05AR17 — -
Marketing authorisation
EU/1/16/1099/003
MA holder
GILEAD SCIENCES IRELAND UC
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Comparator 1

Biktarvy 50 mg/200 mg/25 mg film-coated tablets

PRD6357588 · Product

Active substance
Emtricitabine
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL
Max daily dose
1 U unit(s)
Max total dose
1 U unit(s)
Max treatment duration
48 Week(s)
Authorisation status
Authorised
ATC code
J05AR20 — -
Marketing authorisation
EU/1/18/1289/001
MA holder
GILEAD SCIENCES IRELAND UC
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacion Fls De Lucha Contra El Sida Las Enfermedades Infecciosas Y La Promocion De La Salud Y La Ciencia

6 Total trials 5 Ended
Academic / Non-commercial
Sponsor organisation
Fundacion Fls De Lucha Contra El Sida Las Enfermedades Infecciosas Y La Promocion De La Salud Y La Ciencia
Address
Carretera Canyet S/n
City
Badalona
Postcode
08916
Country
Spain

Scientific contact point

Organisation
Fundacion Fls De Lucha Contra El Sida Las Enfermedades Infecciosas Y La Promocion De La Salud Y La Ciencia
Contact name
Juan Manuel Tiraboschi, PhD

Public contact point

Organisation
Fundacion Fls De Lucha Contra El Sida Las Enfermedades Infecciosas Y La Promocion De La Salud Y La Ciencia
Contact name
Silvia Gel

Locations

1 EU/EEA country · 3 investigational sites

By country

CountryMS statusPlanned subjectsSites
Spain Ongoing, recruitment ended 50 3
Rest of world 0

Investigational sites

Spain

3 sites · Ongoing, recruitment ended
Hospital De La Santa Creu I Sant Pau
Infecciosas, Calle De San Antonio Maria Claret 167, 08025, Barcelona
Hospital Del Mar
Infecciosas, Passeig Maritim De La Barceloneta 25-29, 08003, Barcelona
Bellvitge University Hospital
Infecciosas, Carrer De La Feixa Llarga Sn, 08907, L'hospitalet De Llobregat

Country notifications

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

Country Trial startTrial end Recruitment startRecruitment end Early termination
Spain 2025-01-13 2025-03-03 2026-04-30

Results and documents

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

Documents 6 files

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

TypeTitleVersion
Protocol (for publication) Protocol DORALI_v1_7_16-02-2024 1.7
Summary of Product Characteristics (SmPC) (for publication) Biktarvy_SmPC 1
Summary of Product Characteristics (SmPC) (for publication) Descovy_SmPC 1
Summary of Product Characteristics (SmPC) (for publication) G2_SmPC_Delstrigo_for pub 01MAY2023
Summary of Product Characteristics (SmPC) (for publication) Pifeltro_SmPC 1
Synopsis of the protocol (for publication) Resumen Protocolo DORALI_v1_4_08_11_2023 1.4

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2023-11-15 Spain Acceptable with conditions
2024-02-29
2024-03-11
2 SUBSTANTIAL MODIFICATION SM-1 2024-07-02 Spain Acceptable
2024-09-18
2024-09-18