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

NCT06676410 | Recruiting Phase 2

• 1 other identifier: CP-22-03
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HIV; HIV Infection

Keywords

HIV; AIDS

Outcome Measures

Primary Outcomes (2)

• Variation between V-2 (baseline) and V6 (W12) in relation to the following parameter: • Estimated viral reservoir size by total blood proviral DNA.

  12 weeks

• Variation between V-2 (baseline) and V6 (W12) in relation to the following parameter: CD4+ blood count

  12 weeks

Secondary Outcomes (9)

• Variation between baseline visit and visit 7 (W24) in relation to the following parameter : Estimated viral reservoir size by total proviral DNA

  24 weeks

• Variation between baseline visit and visit 7 (W24) in relation to the following parameter : CD4+ count.

  24 weeks

• Variation between baseline visit and visit 7 (W24) in relation to the following parameter: apoptosis markers

  24 weeks

• Variation between baseline visit and visit 7 (W24) in relation to the following parameter : Cell activation markers

  24 weeks

• Variation between baseline visit and visit 7 (W24) in relation to the following parameter: Inflammation markers

  24 weeks

Study Arms (2)

Codivir®

EXPERIMENTAL

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.

Other: ICF; Behavioral: Eligibility Assessment; Other: Demographic data; Diagnostic Test: Weight, height and BMI; Other: Vital Signs; Diagnostic Test: Medical evaluation; Diagnostic Test: Safety exam; Diagnostic Test: Pregnancy test; Diagnostic Test: Serology; Other: Randomization; Diagnostic Test: Apoptosis markers; Diagnostic Test: Cell activation markers; Diagnostic Test: Inflammation markers; Diagnostic Test: Proviral DNA:; Diagnostic Test: HIV-specific antibodies; Diagnostic Test: HIV viral load (RNA); Behavioral: Codivir® Training; Drug: Dispensing Codivir®; Other: Codivir® Accounting; Other: Concomitant medication; Other: Adverse events

Antiretrovirals (ARTs)

ACTIVE COMPARATOR

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

Other: ICF; Behavioral: Eligibility Assessment; Other: Demographic data; Diagnostic Test: Weight, height and BMI; Other: Vital Signs; Diagnostic Test: Medical evaluation; Diagnostic Test: Safety exam; Diagnostic Test: Pregnancy test; Diagnostic Test: Serology; Other: Randomization; Diagnostic Test: Apoptosis markers; Diagnostic Test: Cell activation markers; Diagnostic Test: Inflammation markers; Diagnostic Test: Proviral DNA:; Diagnostic Test: HIV-specific antibodies; Diagnostic Test: HIV viral load (RNA); Other: Concomitant medication; Other: Adverse events; Drug: Antiretrovirals

Interventions

ICF OTHER

Application of Informed Consent Form.

Antiretrovirals (ARTs); Codivir®

Eligibility Assessment BEHAVIORAL

Assessment of inclusion, exclusion and discontinuation criteria.

Antiretrovirals (ARTs); Codivir®

Demographic data OTHER

Collection of demographic data.

Antiretrovirals (ARTs); Codivir®

Weight, height and BMI DIAGNOSTIC_TEST

Weight and height measurement and body mass index calculation.

Antiretrovirals (ARTs); Codivir®

Vital Signs OTHER

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

Antiretrovirals (ARTs); Codivir®

Medical evaluation DIAGNOSTIC_TEST

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

Antiretrovirals (ARTs); Codivir®

Safety exam 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.

Antiretrovirals (ARTs); Codivir®

Pregnancy test DIAGNOSTIC_TEST

β-HCG in urine in non-sterile women

Antiretrovirals (ARTs); Codivir®

Serology DIAGNOSTIC_TEST

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

Antiretrovirals (ARTs); Codivir®

Randomization OTHER

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

Antiretrovirals (ARTs); Codivir®

Apoptosis markers DIAGNOSTIC_TEST

Caspases and Annexin V.

Antiretrovirals (ARTs); Codivir®

Cell activation markers DIAGNOSTIC_TEST

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

Antiretrovirals (ARTs); Codivir®

Inflammation markers DIAGNOSTIC_TEST

ultrasensitive CRP, D-dimer.

Antiretrovirals (ARTs); Codivir®

Proviral DNA: DIAGNOSTIC_TEST

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

Antiretrovirals (ARTs); Codivir®

HIV-specific antibodies DIAGNOSTIC_TEST

Anti-HIV-1 specific antibody titers in plasma.

Antiretrovirals (ARTs); Codivir®

HIV viral load (RNA) DIAGNOSTIC_TEST

Performed on plasma.

Antiretrovirals (ARTs); Codivir®

Codivir® Training BEHAVIORAL

The participant is trained to self-inject Codivir®

Codivir®

Dispensing Codivir® DRUG

the participant receives Codivir®

Codivir®

Codivir® Accounting OTHER

The Codivir® used since the last visit is accounted for

Codivir®

Concomitant medication OTHER

Record of concomitant medications used.

Antiretrovirals (ARTs); Codivir®

Adverse events OTHER

Collection and recording of adverse events.

Antiretrovirals (ARTs); Codivir®

Antiretrovirals 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

Antiretrovirals (ARTs)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Pregnancy, lactation or plan to become pregnant;
• BMI \< 18.5 kg/m2 at screening;
• Coinfection with HBV (HBSAg +) or HCV;
• Any Grade 3 or 4 clinically significant abnormality according to the Division of AIDS (DAIDS)\* rating scale;
• Any significant acute illness within 1 week before V0.
• Use of any immunomodulatory therapy (including interferon), systemic steroids, or systemic chemotherapy within 4 weeks of screening;
• Active malignancy or ongoing malignancy;
• 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;
• Potential allergy or hypersensitivity to components of the Codivir® formulation.
• Participation in another clinical trial within 12 months of screening.
• Any medical condition that makes the participant unsuitable for the study or increases the risk of participation at the discretion of the investigator.

Sponsors & Collaborators

• Code Pharma: lead
• Galilee CBR: collaborator

Study Sites (1)

RDSS Research Center

São Paulo, 04037-030, Brazil

RECRUITING

MeSH Terms

Conditions

HIV Infections; Acquired Immunodeficiency Syndrome

Interventions

Demography; Body Height; Body Mass Index; Pregnancy Tests; Random Allocation; Anti-Retroviral Agents

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases

Intervention Hierarchy (Ancestors)

Population Characteristics; Epidemiologic Measurements; Public Health; Environment and Public Health; Body Size; Body Weights and Measures; Body Constitution; Physical Examination; Diagnostic Techniques and Procedures; Diagnosis; Physical Appearance, Body; Anthropometry; Investigative Techniques; Physiological Phenomena; Growth; Growth and Development; Biometry; Clinical Laboratory Techniques; Diagnostic Techniques, Obstetrical and Gynecological; Epidemiologic Research Design; Epidemiologic Methods; Research Design; Methods; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Antiviral Agents; Anti-Infective Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Central Study Contacts

Nadya Lisovoder, MD

CONTACT

0524753435; nadyal@galilee-cbr.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: October 1, 2024
• First Posted: November 6, 2024
• Study Start: July 20, 2023
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: November 6, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)