Clinical Trial to Evaluate the Efficacy and Safety of Codivir® in Addition to Standard Antiretroviral Treatment for HIV Infection in Antiretroviral-naïve Participants

NCT ID: NCT06676410

Last Updated: 2024-11-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-07-20

Study Completion Date

2024-12-31

Brief Summary

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The study will begin with a two-week lead-in period (W-2 and W-1), when participants randomized to Codivir® will receive Codivir® 2 mL, 1 subcutaneous injection every day. Participants randomized to Standard Antiretroviral Treatment will wait for the next step.

At V0 (W0, D0) all participants will start the antiretroviral treatment described above.

From V0 (W0, D0) to V6 (W12, D84) participants randomized to Codivir® will receive Codivir® as complementary therapy to the above antiretrovirals on alternate days (every other day).

At V6 (W12, D84) treatment with Codivir® will end. At V7 (W24, D168) participation in the study will end. Viral load will be monitored during the study. In case of failure, participation in the study will be discontinued and the participant will be referred to receive the best treatment available for their case.

Detailed Description

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Conditions

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HIV HIV Infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Randomization

Forty participants with a recent diagnosis of HIV infection, without previous antiretroviral treatment and indication to start antiretroviral treatment, will be randomized as follows:

* 20 participants will receive Standard Antiretroviral Treatment + Codivir
* 20 participants will only receive Standard Antiretroviral Treatment A randomization will be balanced by sex and age.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Codivir®

The study will begin with a two-week lead-in period (W-2 and W-1), when participants randomized to Codivir® will receive Codivir® 2 mL, 1 subcutaneous injection every day. Participants randomized to Standard Antiretroviral Treatment will wait for the next step.

In Weeks 0-24, all participants will receive:

* Single solid formulation (in 1 tablet) 1x/day with:

* Tenofovir (TDF) 300 mg
* Lamivudine (3TC) 300 mg
* Darunavir (DRV) 800 mg, 1x/day
* Ritonavir (RTV) 100 mg, 1x/day From V0 (W0, D0) to V6 (W12, D84) participants randomized to Codivir® will receive Codivir® as complementary therapy to the above antiretrovirals on alternate days (every other day).

At V6 (week 12) treatment with Codivir® will end.

Group Type EXPERIMENTAL

ICF

Intervention Type OTHER

Application of Informed Consent Form.

Eligibility Assessment

Intervention Type BEHAVIORAL

Assessment of inclusion, exclusion and discontinuation criteria.

Demographic data

Intervention Type OTHER

Collection of demographic data.

Weight, height and BMI

Intervention Type DIAGNOSTIC_TEST

Weight and height measurement and body mass index calculation.

Vital Signs

Intervention Type OTHER

HR, BP and FR and T°, in addition to oximetry.

Medical evaluation

Intervention Type DIAGNOSTIC_TEST

Medical history and physical examination at screening. In other consultations, the medical evaluation is focused on viral load, CD4+ and new complaints.

Safety exam

Intervention Type DIAGNOSTIC_TEST

Blood collection for safety laboratory exams. Blood count, Na, K, U, C, amylase, total cholesterol and fractions, triglycerides, coagulation tests (TTTP, TT, platelets), TGO, TGP, AP, GGT, glycated hemoglobin, total bilirubin and fractions, creatine kinase and CKmB and urine I.

Pregnancy test

Intervention Type DIAGNOSTIC_TEST

β-HCG in urine in non-sterile women

Serology

Intervention Type DIAGNOSTIC_TEST

HBV (HBsAg, Anti-HBc) and HCV (anti-HCV-Ab).

Randomization

Intervention Type OTHER

Assignment to the Standard Antiretroviral Treatment + Codivir® group or the Standard Antiretroviral Treatment only group

Apoptosis markers

Intervention Type DIAGNOSTIC_TEST

Caspases and Annexin V.

Cell activation markers

Intervention Type DIAGNOSTIC_TEST

PBMCs will be isolated by density gradient centrifugation. The cells will then be tested for CD4+, CD8+, CD38 and HLA DR

Inflammation markers

Intervention Type DIAGNOSTIC_TEST

ultrasensitive CRP, D-dimer.

Proviral DNA:

Intervention Type DIAGNOSTIC_TEST

Total HIV DNA will be measured to estimate the size of the viral reservoir throughout the preparation.

HIV-specific antibodies

Intervention Type DIAGNOSTIC_TEST

Anti-HIV-1 specific antibody titers in plasma.

HIV viral load (RNA)

Intervention Type DIAGNOSTIC_TEST

Performed on plasma.

Codivir® Training

Intervention Type BEHAVIORAL

The participant is trained to self-inject Codivir®

Dispensing Codivir®

Intervention Type DRUG

the participant receives Codivir®

Codivir® Accounting

Intervention Type OTHER

The Codivir® used since the last visit is accounted for

Concomitant medication

Intervention Type OTHER

Record of concomitant medications used.

Adverse events

Intervention Type OTHER

Collection and recording of adverse events.

Antiretrovirals (ARTs)

In Weeks 0-24, all participants will receive:

* Single solid formulation (in 1 tablet) 1x/day with:

* Tenofovir (TDF) 300 mg
* Lamivudine (3TC) 300 mg
* Darunavir (DRV) 800 mg, 1x/day
* Ritonavir (RTV) 100 mg, 1x/day

Group Type ACTIVE_COMPARATOR

ICF

Intervention Type OTHER

Application of Informed Consent Form.

Eligibility Assessment

Intervention Type BEHAVIORAL

Assessment of inclusion, exclusion and discontinuation criteria.

Demographic data

Intervention Type OTHER

Collection of demographic data.

Weight, height and BMI

Intervention Type DIAGNOSTIC_TEST

Weight and height measurement and body mass index calculation.

Vital Signs

Intervention Type OTHER

HR, BP and FR and T°, in addition to oximetry.

Medical evaluation

Intervention Type DIAGNOSTIC_TEST

Medical history and physical examination at screening. In other consultations, the medical evaluation is focused on viral load, CD4+ and new complaints.

Safety exam

Intervention Type DIAGNOSTIC_TEST

Blood collection for safety laboratory exams. Blood count, Na, K, U, C, amylase, total cholesterol and fractions, triglycerides, coagulation tests (TTTP, TT, platelets), TGO, TGP, AP, GGT, glycated hemoglobin, total bilirubin and fractions, creatine kinase and CKmB and urine I.

Pregnancy test

Intervention Type DIAGNOSTIC_TEST

β-HCG in urine in non-sterile women

Serology

Intervention Type DIAGNOSTIC_TEST

HBV (HBsAg, Anti-HBc) and HCV (anti-HCV-Ab).

Randomization

Intervention Type OTHER

Assignment to the Standard Antiretroviral Treatment + Codivir® group or the Standard Antiretroviral Treatment only group

Apoptosis markers

Intervention Type DIAGNOSTIC_TEST

Caspases and Annexin V.

Cell activation markers

Intervention Type DIAGNOSTIC_TEST

PBMCs will be isolated by density gradient centrifugation. The cells will then be tested for CD4+, CD8+, CD38 and HLA DR

Inflammation markers

Intervention Type DIAGNOSTIC_TEST

ultrasensitive CRP, D-dimer.

Proviral DNA:

Intervention Type DIAGNOSTIC_TEST

Total HIV DNA will be measured to estimate the size of the viral reservoir throughout the preparation.

HIV-specific antibodies

Intervention Type DIAGNOSTIC_TEST

Anti-HIV-1 specific antibody titers in plasma.

HIV viral load (RNA)

Intervention Type DIAGNOSTIC_TEST

Performed on plasma.

Concomitant medication

Intervention Type OTHER

Record of concomitant medications used.

Adverse events

Intervention Type OTHER

Collection and recording of adverse events.

Antiretrovirals

Intervention Type DRUG

Tenofovir - inhibits HIV-1 reverse transcriptase activity by competing with the natural substrate, deoxyadenosine 5'-triphosphate and, upon incorporation into DNA, causes DNA chain termination.

* Lamivudine - potent selective inhibitor of HIV-1 and HIV-2 replication in vitro.
* Darunavir - prevents the formation of mature infective viral particles, indicated for the treatment of the human immunodeficiency virus (HIV), which causes AIDS.
* Ritonavir: antiretroviral protease inhibitor, widely used in combination with other protease inhibitors in the therapy and prevention of HIV infection, which causes the syndrome acquired immunodeficiency (AIDS).
* Single solid formulation (in 1 tablet) 1x/day with:
* Tenofovir (TDF) 300 mg
* Lamivudine (3TC) 300 mg
* Darunavir (DRV) 800 mg, 1x/day
* Ritonavir (RTV) 100 mg, 1x/day

Interventions

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ICF

Application of Informed Consent Form.

Intervention Type OTHER

Eligibility Assessment

Assessment of inclusion, exclusion and discontinuation criteria.

Intervention Type BEHAVIORAL

Demographic data

Collection of demographic data.

Intervention Type OTHER

Weight, height and BMI

Weight and height measurement and body mass index calculation.

Intervention Type DIAGNOSTIC_TEST

Vital Signs

HR, BP and FR and T°, in addition to oximetry.

Intervention Type OTHER

Medical evaluation

Medical history and physical examination at screening. In other consultations, the medical evaluation is focused on viral load, CD4+ and new complaints.

Intervention Type DIAGNOSTIC_TEST

Safety exam

Blood collection for safety laboratory exams. Blood count, Na, K, U, C, amylase, total cholesterol and fractions, triglycerides, coagulation tests (TTTP, TT, platelets), TGO, TGP, AP, GGT, glycated hemoglobin, total bilirubin and fractions, creatine kinase and CKmB and urine I.

Intervention Type DIAGNOSTIC_TEST

Pregnancy test

β-HCG in urine in non-sterile women

Intervention Type DIAGNOSTIC_TEST

Serology

HBV (HBsAg, Anti-HBc) and HCV (anti-HCV-Ab).

Intervention Type DIAGNOSTIC_TEST

Randomization

Assignment to the Standard Antiretroviral Treatment + Codivir® group or the Standard Antiretroviral Treatment only group

Intervention Type OTHER

Apoptosis markers

Caspases and Annexin V.

Intervention Type DIAGNOSTIC_TEST

Cell activation markers

PBMCs will be isolated by density gradient centrifugation. The cells will then be tested for CD4+, CD8+, CD38 and HLA DR

Intervention Type DIAGNOSTIC_TEST

Inflammation markers

ultrasensitive CRP, D-dimer.

Intervention Type DIAGNOSTIC_TEST

Proviral DNA:

Total HIV DNA will be measured to estimate the size of the viral reservoir throughout the preparation.

Intervention Type DIAGNOSTIC_TEST

HIV-specific antibodies

Anti-HIV-1 specific antibody titers in plasma.

Intervention Type DIAGNOSTIC_TEST

HIV viral load (RNA)

Performed on plasma.

Intervention Type DIAGNOSTIC_TEST

Codivir® Training

The participant is trained to self-inject Codivir®

Intervention Type BEHAVIORAL

Dispensing Codivir®

the participant receives Codivir®

Intervention Type DRUG

Codivir® Accounting

The Codivir® used since the last visit is accounted for

Intervention Type OTHER

Concomitant medication

Record of concomitant medications used.

Intervention Type OTHER

Adverse events

Collection and recording of adverse events.

Intervention Type OTHER

Antiretrovirals

Tenofovir - inhibits HIV-1 reverse transcriptase activity by competing with the natural substrate, deoxyadenosine 5'-triphosphate and, upon incorporation into DNA, causes DNA chain termination.

* Lamivudine - potent selective inhibitor of HIV-1 and HIV-2 replication in vitro.
* Darunavir - prevents the formation of mature infective viral particles, indicated for the treatment of the human immunodeficiency virus (HIV), which causes AIDS.
* Ritonavir: antiretroviral protease inhibitor, widely used in combination with other protease inhibitors in the therapy and prevention of HIV infection, which causes the syndrome acquired immunodeficiency (AIDS).
* Single solid formulation (in 1 tablet) 1x/day with:
* Tenofovir (TDF) 300 mg
* Lamivudine (3TC) 300 mg
* Darunavir (DRV) 800 mg, 1x/day
* Ritonavir (RTV) 100 mg, 1x/day

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Male or female sex;
2. Age ≥ 18 years;
3. HIV infection confirmed by serology (Ab for HIV1/HIV2) and HIV1/HIV2 RNA test;
4. Naive for antiretroviral treatment;
5. Viral load \> 1,000 and \< 50,000 copies/mL;
6. CD4 T lymphocyte (CD4) cell count \>350 cells/mm3;
7. Body weight at V -1 \> 50 Kg;
8. Signature of the ICF.

Exclusion Criteria

1. Pregnancy, lactation or plan to become pregnant;
2. BMI \< 18.5 kg/m2 at screening;
3. Coinfection with HBV (HBSAg +) or HCV;
4. Any Grade 3 or 4 clinically significant abnormality according to the Division of AIDS (DAIDS)\* rating scale;
5. Any significant acute illness within 1 week before V0.
6. Use of any immunomodulatory therapy (including interferon), systemic steroids, or systemic chemotherapy within 4 weeks of screening;
7. Active malignancy or ongoing malignancy;
8. Changes in safety tests: neutrophil count \< 1000 u/L; Hb \< 9.0 gm/dl; platelet \< 75,000 u/L; creatinine \> 1.5 mg/dl, direct bilirubin \> 85 μmol/l, AST or ALT \> 2.5 X ULN;
9. Potential allergy or hypersensitivity to components of the Codivir® formulation.
10. Participation in another clinical trial within 12 months of screening.
11. Any medical condition that makes the participant unsuitable for the study or increases the risk of participation at the discretion of the investigator.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Galilee CBR

INDUSTRY

Sponsor Role collaborator

Code Pharma

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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RDSS Research Center

São Paulo, , Brazil

Site Status RECRUITING

Countries

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Brazil

Central Contacts

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Nadya Lisovoder, MD

Role: CONTACT

0524753435

Facility Contacts

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Siderleny Martins

Role: primary

+55 19 98911-9721

Other Identifiers

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CP-22-03

Identifier Type: -

Identifier Source: org_study_id

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