Proof of Concept Treatment Study of Orally Administered VH4004280 or VH4011499 in HIV-1 Infected Adults (CINNAMON)

A Randomized, Double-Blind (Sponsor Unblinded), Placebo-Controlled, Phase 2a Trial to Investigate the Antiviral Effect, Safety, Tolerability and Pharmacokinetics of Orally Administered Investigational Capsid Inhibitor Monotherapy in HIV-1 Infected Treatment-Naïve Adults

The primary purpose of the study is to evaluate the antiviral activity of orally administered VH4004280 and VH4011499 monotherapy over 10 days in human immunodeficiency virus (HIV-1) infected Treatment-Naïve (TN) participants.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Antiretroviral therapy; Drug: VH4004280; Drug: VH4004280 Matching Placebo; Drug: VH4011499; Drug: VH4011499 Matching Placebo

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1023
    • GSK Investigational Site
  • Buenos Aires, Argentina, C1425AGC
    • GSK Investigational Site
  • Buenos Aires, Argentina, C1202ABB
    • GSK Investigational Site
  • Ciudad Autonoma de Bueno, Argentina, C1405CKC
    • GSK Investigational Site
• Canada
  • Quebec
    • Montreal, Quebec, Canada, H2L 4P9
      • GSK Investigational Site
• France
  • Marseille, France, 13003
    • GSK Investigational Site
  • Nantes, France, 44093
    • GSK Investigational Site
  • Paris, France, 75018
    • GSK Investigational Site
• Germany
  • Cologne, Germany, 50937
    • GSK Investigational Site
• Italy
  • Milan, Italy, 20157
    • GSK Investigational Site
• Mexico
  • Guadalajara, Mexico, 44160
    • GSK Investigational Site
  • Mexico City, Mexico, 06760
    • GSK Investigational Site
• Spain
  • Barcelona, Spain, 08907
    • GSK Investigational Site
  • Barcelona, Spain, 08916
    • GSK Investigational Site
  • Madrid, Spain, 28046
    • GSK Investigational Site
  • Madrid, Spain, 28034
    • GSK Investigational Site
• United Kingdom
  • London, United Kingdom, SE5 8RX
    • GSK Investigational Site
• United States
  • California
    • Bakersfield, California, United States, 93301
      • GSK Investigational Site
  • Florida
    • DeLand, Florida, United States, 32720
      • GSK Investigational Site
  • New Jersey
    • Newark, New Jersey, United States, 07102
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants who are overtly healthy (other than HIV-1 infection).
• Screening cluster of differentiation-4 (CD4+) T-cell count greater than or equal to (≥)200 cells/microliter (µL).
• Documented HIV-1 infection and Screening plasma HIV-1 RNA ≥3000 copies/milliliter (mL).
• Treatment-naïve: Defined as no antiretroviral therapy received after the diagnosis of HIV-1 infection. Prior use of oral pre-exposure prophylaxis (PreP) is permitted. Prior use of parenteral PreP is exclusionary.
• Has body mass index (BMI) within the range of 18.5-31.0 kilograms per meter square (kg/m^2).
• Participants male at birth must use male condoms and participants female at birth who are of childbearing potential must be using acceptable forms of birth control.
• Participants capable of giving signed informed consent.
• Participant must be willing and able to start locally accessible and commercially available combination antiretroviral therapy after the monotherapy period.

Exclusion Criteria:

• Women who are breastfeeding or plan to become pregnant or breast feed during the study.
• Participants with acute HIV infection.
• Any evidence of an active Centers for Disease Control and Prevention (CDC) Stage 3 disease.
• Untreated syphilis infection.
• Ongoing malignancy other than certain localised malignancies.
• Treatment with immunomodulating agents or any agent with known anti-HIV activity.
• Has exclusionary psychiatric, hepatic, cardiovascular gastrointestinal, renal condition.
• Participant having any condition which, in the opinion of the investigator, may interfere with the absorption, distribution, metabolism or excretion of the study drugs or render the participant unable to take oral medication.
• Participants having exclusionary electrocardiogram (ECG) findings.
• Participants who have been exposed to any prohibited medication or vaccine.
• Participant positive for hepatitis B or hepatitis C.
• Participants with exclusionary safety laboratory (e.g Grade 3 or greater abnormality).
• Participants who have positive results for illicit drug use, regular use of drugs of abuse and/or excessive alcohol use.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1a: VH4004280 Dose Level 1; Participants received a single dose of VH4004280 Dose Level 1 (low concentration) on Day 1 (evaluated for a 10-day period). On Day 11, participants switched to an open-label antiretroviral therapy (ART) up to day 39.	Drug: Antiretroviral therapy; Antiretroviral therapy was administered as available and as per investigator's recommendation.; Drug: VH4004280; VH4004280 was administered as tablets orally at Day 1.
Experimental: Part 1a: VH4004280 Dose Level 2; Participants received a single dose of VH4004280 Dose Level 2 (medium concentration) on Day 1 (evaluated for a 10-day period). On Day 11, participants switched to an open-label ART up to day 39.	Drug: Antiretroviral therapy; Antiretroviral therapy was administered as available and as per investigator's recommendation.; Drug: VH4004280; VH4004280 was administered as tablets orally at Day 1.
Experimental: Part 2a: VH4004280 pre-specified dose; Participants received a single pre-specified dose of VH4004280 (high concentration) on Day 1 (evaluated for a 10-day period). On Day 11, participants switched to an open-label ART up to day 39.	Drug: Antiretroviral therapy; Antiretroviral therapy was administered as available and as per investigator's recommendation.; Drug: VH4004280; VH4004280 was administered as tablets orally at Day 1.
Placebo Comparator: Matching placebo for VH4004280; Participants received a matching placebo for VH4004280 on Day 1 (evaluated for a 10-day period). On Day 11, participants switched to an open-label ART up to day 39.	Drug: Antiretroviral therapy; Antiretroviral therapy was administered as available and as per investigator's recommendation.; Drug: VH4004280 Matching Placebo; VH4004280 Matching Placebo was administered as tablets orally at Day 1.
Experimental: Part 1b: VH4011499 Dose Level 1; Participants received a single dose of VH4011499 Dose Level 1 (low concentration) on Day 1 and Day 6 (evaluated for a 10-day period). On Day 11, participants had the option to switch to an open-label ART up to day 39.	Drug: Antiretroviral therapy; Antiretroviral therapy was administered as available and as per investigator's recommendation.; Drug: VH4011499; VH4011499 was administered as tablets orally at Day 1 and Day 6.
Experimental: Part 1b: VH4011499 Dose Level 2; Participants received a single dose of VH4011499 Dose Level 2 (medium concentration) on Day 1 and Day 6 (evaluated for a 10-day period). On Day 11, participants switched to an open-label ART up to day 39.	Drug: Antiretroviral therapy; Antiretroviral therapy was administered as available and as per investigator's recommendation.; Drug: VH4011499; VH4011499 was administered as tablets orally at Day 1 and Day 6.; Drug: VH4011499 Matching Placebo; VH4011499 Matching Placebo was administered as tablets orally at Day 1 and Day 6.
Experimental: Part 2b: VH4011499 pre-specified dose; Participants received a single pre-specified dose of VH4011499 (high concentration) on Day 1 and Day 6 (evaluated for a 10-day period). On Day 11, participants switched to an open-label ART up to day 39.	Drug: Antiretroviral therapy; Antiretroviral therapy was administered as available and as per investigator's recommendation.; Drug: VH4011499; VH4011499 was administered as tablets orally at Day 1 and Day 6.
Placebo Comparator: Matching placebo for VH4011499; Participants received a matching placebo for VH4011499 on Day 1 and Day 6 (evaluated for a 10-day period). On Day 11, participants switched to an open-label ART up to day 39.	Drug: Antiretroviral therapy; Antiretroviral therapy was administered as available and as per investigator's recommendation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Monotherapy, VH4004280: Maximum Change From Baseline (Day 1) in Plasma HIV-1 Ribonucleic Acid (RNA) log10	Plasma samples were collected for quantitative analysis of plasma HIV-1 RNA. Maximum change from baseline was calculated by subtracting the baseline value from the post-dose visit value when the plasma HIV-1 RNA reached its minimum level up to Day 11 (inclusive). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. The results were expressed as log10 copies per milliliter (log10 c/mL).	From Baseline (Day 1) and up to Day 11
Monotherapy, VH4011499: Maximum Change From Baseline (Day 1) in Plasma HIV-1 RNA log10	Plasma samples were collected for quantitative analysis of plasma HIV-1 RNA. Maximum change from baseline was calculated by subtracting the baseline value from the post-dose visit value when the plasma HIV-1 RNA reached its minimum level up to Day 11 (inclusive). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.	From Baseline (Day 1) and up to Day 11

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Monotherapy: Number of Participants With Any Adverse Events (AEs)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any = occurrence of the event regardless of intensity grade or relation to the study intervention.	From Baseline (Day 1) and up to Day 11
Follow-up: Number of Participants With Any AEs	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any = occurrence of the event regardless of intensity grade or relation to the study intervention.	From Day 11 and up to Day 39
Monotherapy: Number of Participants With AEs by Severity	Severity was rated according to the Division of Acquired Immunodeficiency Syndrome (DAIDS) grading criteria, where Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = potentially life-threatening, Grade 5 = death.	From Baseline (Day 1) and up to Day 11
Follow-up: Number of Participants With AEs by Severity	Severity was rated according to the DAIDS grading criteria, where Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = potentially life-threatening, Grade 5 = death.	From Day 11 and up to Day 39
Monotherapy: Number of Participants With AEs Leading to Study Treatment Discontinuation	'Discontinuation' of study intervention refers to any participant who has not received all planned doses of study intervention.	From Baseline (Day 1) and up to Day 11
Monotherapy and Follow-up, VH4004280: Change From Baseline for Liver Panel Laboratory Parameters - Total Bilirubin and Direct Bilirubin	Change from Baseline values for liver panel laboratory parameters total bilirubin and direct bilirubin were summarised. Change from baseline was calculated by subtracting the baseline value from the post-dose visit value.Standard deviation (SD) = 0.0000 is defined as following: if all participants analyzed for a specific parameter at a specific time point have the same value, then SD is equal with 0.0000.	At Baseline (Day 1) and at Days 2, 4, 6, 7, 9, 11, 18, 25, 32 and 39
Monotherapy and Follow-up, VH4011499: Change From Baseline for Liver Panel Laboratory Parameters - Total Bilirubin and Direct Bilirubin	Change from Baseline values for liver panel laboratory parameters total bilirubin and direct bilirubin were summarised. Change from baseline was calculated by subtracting the baseline value from the post-dose visit value. SD = 0.0000 is defined as following: if all participants analyzed for a specific parameter at a specific time point have the same value, then SD is equal with 0.0000.	At Baseline (Day 1) and at Days 2, 4, 6, 7, 9, 11, 18, 25, 32 and 39
Monotherapy and Follow-up, VH4004280: Change From Baseline for Liver Panel Laboratory Parameters - Alanine Aminotransferace (ALT), Alkaline Phosphatase (ALP) and Aspartate Aminotransferase (AST)	Change from Baseline values for liver panel laboratory parameters ALT, ALP and AST were summarised. Change from baseline was calculated by subtracting the baseline value from the post-dose visit value.	At Baseline (Day 1) and at Days 2, 4, 6, 7, 9, 11, 18, 25, 32 and 39
Monotherapy and Follow-up, VH4011499: Change From Baseline for Liver Panel Laboratory Parameters - ALT, ALP and AST	Change from Baseline values for liver panel laboratory parameters ALT, ALP and AST were summarised. Change from baseline was calculated by subtracting the baseline value from the post-dose visit value.	At Baseline (Day 1) and at Days 2, 4, 6, 7, 9, 11, 18, 25, 32 and 39
Monotherapy and Follow-up, VH4004280: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Laboratory Parameters - Total Bilirubin and Direct Bilirubin	Laboratory abnormalities were graded according to DAIDS grading table Version 2.1 where grades were defined based on numeric criteria as follows Grade 0: participants with missing baseline values; Grade 1: Mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences.	From Baseline (Day 1) and up to Day 39
Monotherapy and Follow-up, VH4011499: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Laboratory Parameters - Total Bilirubin and Direct Bilirubin	Laboratory abnormalities were graded according to DAIDS grading table Version 2.1 where grades were defined based on numeric criteria as follows Grade 0: participants with missing baseline values; Grade 1: Mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences.	From Baseline (Day 1) and up to Day 39
Monotherapy and Follow-up, VH4004280: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Laboratory Parameters - ALT, ALP and AST	Laboratory abnormalities were graded according to DAIDS grading table Version 2.1 where grades were defined based on numeric criteria as follows Grade 0: participants with missing baseline values; Grade 1: Mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences.	From Baseline (Day 1) and up to Day 39
Monotherapy and Follow-up, VH4011499: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Laboratory Parameters - ALT, ALP and AST	Laboratory abnormalities were graded according to DAIDS grading table Version 2.1 where grades were defined based on numeric criteria as follows Grade 0: participants with missing baseline values; Grade 1: Mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences.	From Baseline (Day 1) and up to Day 39
Monotherapy, VH4004280: Maximum Observed Plasma Drug Concentration (Cmax)	Cmax is defined as the maximum concentration of the drug in plasma.	After dose administration at Day 1
Monotherapy, VH4011499: Cmax	Cmax is defined as the maximum concentration of the drug in plasma.	After dose administration at Day 1 and Day 6
Monotherapy, VH4004280: Time to Maximum Observed Plasma Drug Concentration (Tmax)	Tmax is a measure of the time required to reach the maximum concentration of the drug.	After dose administration at Day 1
Monotherapy, VH4011499: Tmax	Tmax is a measure of the time required to reach the maximum concentration of the drug.	After dose administration at Day 1 and Day 6
Monotherapy, VH4004280: Plasma Concentration at Day 11 (C11)	C11 is defined as the concentration of the drug in plasma at Day 11.	At Day 11
Monotherapy, VH4011499: C11	C11 is defined as the concentration of the drug in plasma at Day 11.	At Day 11
Monotherapy, VH4004280: Change in Plasma HIV-1 RNA From Baseline	Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from baseline was calculated by subtracting the baseline value from the post-dose visit value.	At Baseline (Day 1) and Day 11
Monotherapy, VH4011499: Change in Plasma HIV-1 RNA From Baseline	Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from baseline was calculated by subtracting the baseline value from the post-dose visit value.	At Baseline (Day 1) and Day 11

Collaborators and Investigators

• Sponsor: ViiV Healthcare

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2023
• Primary Completion (Actual): June 24, 2024
• Study Completion (Actual): June 24, 2024

Study Registration Dates

• First Submitted: August 23, 2023
• First Submitted That Met QC Criteria: September 12, 2023
• First Posted (Actual): September 15, 2023

Study Record Updates

• Last Update Posted (Estimated): September 30, 2025
• Last Update Submitted That Met QC Criteria: September 9, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: HIV-1; VH4011499; Monotherapy; Treatment Naïve; Phase 2a; VH4004280
• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; HIV Infections; Therapeutics; Drug Therapy; Drug Therapy, Combination; Antiretroviral Therapy, Highly Active
• Other Study ID Numbers: 218307; 2023-505350-18-00 (Other Identifier: EU CT number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The sponsor will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to: https://www.viiv-studyregister.com/documents/About_ViiV_Patient_Level_Data_Sharing_Final_25Sep2023.pdf.
• IPD Sharing Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• IPD Sharing Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes