Safety and Efficacy Study of Vaccine Schedule With Ad26.Mos.HIV and MVA-Mosaic in Human Immunodeficiency Virus (HIV)-Infected Adults

NCT02919306 | Completed Phase 1 Results DMC

• 2 other identifiers: CR108161VAC89220HTX1001
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to assess: 1 safety and tolerability of adenovirus serotype 26 (Ad26) prime and Modified Vaccinia Ankara (MVA) boost versus placebo in participants on suppressive antiretroviral therapy (ART) that was initiated during acute Human Immunodeficiency Virus (HIV) infection; 2) Measure the frequency and duration of sustained viremic control after receiving Ad26 prime/MVA boost or placebo, defined as greater than 24 weeks with plasma HIV ribonucleic acid (RNA) lesser than (\<)50 copies/ml after antiretroviral (ARV) analytical treatment interruption (ATI).

Conditions

Human Immunodeficiency Virus

Outcome Measures

Primary Outcomes (14)

• Percentage of Participants With Grade 3 or 4 Solicited Local Adverse Events (AEs)

  Solicited local AE of grade 3 or 4 and that is thought to be related to study vaccine were reported. An AE is any untoward medical occurrence in a clinical study participant administered a investigational or non-investigational medicinal product. An AE does not necessarily have a causal relationship with the treatment. Solicited local AEs (at injection site) included pain/tenderness, erythema, induration, swelling, itching and warmth were collected and reported for 7 days after each vaccination.

  Up to Week 49 (7 days post each vaccination)

• Percentage of Participants With Grade 3 or 4 Solicited Systemic AEs

  Solicited systemic AE of grade 3 or 4 and that is thought to be related to study vaccine were reported. Solicited systemic AEs included fever (defined as body temperature of 38.0-degree celsius or higher), fatigue, headache, myalgia, arthralgia, chills, nausea, vomiting, rashes, and general itching.

  Up to Week 49 (7 days post each vaccination)

• Percentage of Participants With Grade 3 or 4 Unsolicited AEs

  Unsolicited AE with worst severity grade 3 or 4 and that is thought to be related to study vaccine were reported. Unsolicited AEs were defined as events that participants experienced but were not specifically asked about.

  Up to Week 52 (28 days after each vaccination)

• Percentage of Participants With Grade 3 or 4 Related AEs

  Related AEs of grade 3 or 4 and that is thought to be related to study vaccine were reported.

  Up to Week 52 (28 days after each vaccination)

• Percentage of Participants With Solicited Local AEs for 7 Days After Each Vaccination

  An AE is any untoward medical occurrence in a clinical study participant administered a investigational or non-investigational medicinal product. An AE does not necessarily have a causal relationship with the treatment. Solicited local AEs (at injection site) included pain/tenderness, erythema, induration, swelling, itching and warmth were collected and reported for 7 days after each vaccination.

  Up to Week 49 (7 days post each vaccination)

• Percentage of Participants With Solicited Systemic AEs for 7 Days After Each Vaccination

  Solicited systemic AEs included fever (defined as body temperature of 38.0-degree celsius or higher), fatigue, headache, myalgia, arthralgia, chills, nausea, vomiting, rashes, and general itching were collected and reported for 7 days after each vaccination.

  Up to Week 49 (7 days after each vaccination)

• Percentage of Participants With Unsolicited AEs 28 Days After Each Vaccination

  Unsolicited AEs were defined as events that participants experienced but were not specifically asked about.

  Up to Week 52 (28 days after each vaccination)

• Percentage of Participants With Related AEs and Serious Adverse Events (SAEs)

  An AE is any untoward medical occurrence in a clinical study participant administered a investigational or non-investigational medicinal product. An AE does not necessarily have a causal relationship with the treatment. A SAE is any AE that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect and is a suspected transmission of any infectious agent via a medicinal product.

  Up to Week 52 (28 days after each vaccination)

• Percentage of Participants With AEs Leading to Discontinuation of Study Vaccination

  Percentage of participants with AEs leading to discontinuation of study vaccination were reported.

  Up to Week 96

• Percentage of Participants With AEs

  Percentage of participants with AEs were reported.

  Up to Week 52 (28 days after each vaccination)

• Percentage of Participants With Worst Laboratory Toxicity Grades 1, 2, 3, and 4 and Non-graded Serum Chemistry Abnormalities

  Percentage of participants with worst laboratory grades 1 (mild), 2 (moderate), 3 (severe), and 4 (potentially life-threatening) and non-graded serum chemistry abnormalities were reported. Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, creatine, hyperglycemia, hypoglycemia, gamma-gutamyl transferase, chloride, urea nitrogen, and bilirubin. The parameters not represented in the grading scale, abnormalities were indicated as being 'high' or 'low' or 'abnormal'.

  Up to Week 96

• Percentage of Participants With Worst Laboratory Toxicity Grade 1 and Non-graded Hematology Abnormalities

  Percentage of participants with worst laboratory toxicity grade 1 (mild) and non-graded hematology abnormalities were reported. Hematology parameters included absolute neutrophil count, basophils/leukocytes, eosinophils/leukocytes, hematocrit, lymphocytes/leukocytes, monocytes/leukocytes, neutrophils/leukocytes, erythrocytes, hematocrit, neutrophils, basophils, eosinophils, eosinophils/leukocytes, monocytes, neutrophils and platelet count. The parameters not represented in the grading scale, abnormalities were indicated as being 'high' or 'low' or 'abnormal'.

  Up to Week 96

• Percentage of Participants With Sustained Viremic Control (Human Immunodeficiency Virus [HIV] Ribonucleic Acid [RNA] Less Than [<]50 Copies Per Milliliter [Copies/mL]) During ATI Phase

  Percentage of participants with sustained viremic control (HIV RNA \<50 copies/mL) during ATI phase were reported.

  From Week 60 to Week 96

• Duration of Sustained Viremic Control With HIV RNA <50 Copies/mL During ATI Phase

  Duration of sustained viremic control With HIV RNA \<50 copies/mL during ATI Phase was reported.

  From Week 60 to Week 96

Secondary Outcomes (12)

• Total HIV Deoxyribonucleic Acid (DNA) Levels Over Time

  From Week 60 to Week 96

• Change in Cluster of Differentiation (CD)4 Count Over Time

  Baseline and from Week 60 to Week 96

• Time to Reinitiating ART

  Up to Week 96

• Number of Participants With Acute Retroviral Syndrome Post-ARV ATI

  From Week 60 to Week 96

• Duration of Acute Retroviral Syndrome Post-ARV ATI

  From Week 60 to Week 96

Study Arms (2)

Ad26.Mos.HIV Vaccine or MVA mosaic Vaccine

EXPERIMENTAL

Participants will receive adenovirus serotype 26-Mosaic -Human Immunodeficiency Virus (Ad26.Mos.HIV) 0.5 milliliter (mL) injection intramuscularly (containing 5 \* 10\^10 viral particles \[vp\]) at Weeks 0 and 12 followed by modified Vaccinia Ankara-Mosaic (MVA mosaic) 0.5 mL injection (containing 10\^8 Plaque-forming unit \[pfu\]) at Week 24 and 48.

Biological: Ad26.Mos.HIV; Biological: MVA-Mosaic

Placebo

PLACEBO COMPARATOR

0.5 mL Sodium Chloride Injection United States Pharmacopeia (USP) 0.9% will be administered by intramuscular (IM) injection.

Drug: Placebo

Interventions

Ad26.Mos.HIV BIOLOGICAL

Recombinant replication-deficient Ad26 vectored vaccine and consists of 3 Ad26 vectors, one containing a mosaic insert of envelope (Env) sequence, and 2 vectors containing mosaic inserts of Gag and Pol sequences (Ad26.Mos.1.Env + Ad26.Mos1.Gag-Pol + Ad26.Mos2.Gag-Pol). Total dose is 5\*10\^10 viral particle per 0.5 milliliter (mL) injection administered intramuscularly.

Ad26.Mos.HIV Vaccine or MVA mosaic Vaccine

MVA-Mosaic BIOLOGICAL

Recombinant live attenuated MVA virus-vectored vaccine that has been genetically engineered to express 2 mosaic Gag, Pol, and Env sequences (Mosaic 1 and Mosaic 2). Total dose is 10\^8 plaque-forming unit per 0.5 mL injection administered intramuscularly.

Ad26.Mos.HIV Vaccine or MVA mosaic Vaccine

Placebo DRUG

Participants will receive placebo intramuscularly Weeks 0, 12, 24 and 48.

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Confirmed human immunodeficiency virus (HIV)-1 infected and started antiretroviral therapy (ART) during acute infection (Fiebig stages I, II, III or IV) as part of trial RV254
• Treatment with current stable antiretroviral therapy (ART) (no changes to treatment) for at least 4 weeks prior to screening
• All female participants of childbearing potential must have a negative serum pregnancy test (beta human chorionic gonadotropin) at the screening visit, and a negative urine pregnancy test prior to vaccination on Day 1 and prior to subsequent study vaccinations
• HIV ribonucleic acid (RNA) less than (\<)50 copies per milliliter (copies/ml) for at least 48 weeks at screening: a) One blip of HIV RNA greater than (\>)50 and \<200 copies/ml within 48 weeks is acceptable, provided that the most recent (before screening) HIV RNA \<50 copies/ml
• Laboratory criteria during screening: a) Hemoglobin: Women: greater than or equal to \>=11 gram/deciliter (g/dL); Men \>=12.5 g/dL, b) White cell count: 2,500 to 11,000 cells per cubic millimeter (cells/mm\^3), c) Platelets: 125,000 to 450,000 per mm\^3, d) Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less than or equal to \<=1.5x institutional upper limits of normal (ULN), e) Creatinine \<=1.5x institutional ULN, f) CD4 \> 400 cells/mm\^3, g) Troponin \<1x ULN
• A woman must be either: a) Not of childbearing potential: postmenopausal (\>45 years of age with amenorrhea for at least 2 years, or any age with amenorrhea for at least 6 months and a serum follicle stimulation hormone \[FSH\] level \>40 International Units Per Liter (IU/L); surgically sterile; or b) Of child-bearing potential and practicing an effective double method of birth control (example, prescription oral contraceptives, contraceptive injections, intrauterine device, contraceptive patch, or vaginal ring, in conjunction with either a female condom or one of the methods for male contraception before entry and through 3 months after the last vaccination

You may not qualify if:

• Receipt of any vaccine within 30 days prior to the first vaccination or plans to receive within 30 days post-vaccination. In the case of medically indicated vaccines, the vaccination should be given at least 2 weeks before or after the first vaccination. However, if a vaccine is indicated in a post exposure setting (example, rabies or tetanus), it must take priority over the study vaccine and same rules will apply to subsequent study vaccinations
• Any history of HIV-related illness under Centers for Disease Control and Prevention (CDC) category C
• History of myocarditis, pericarditis, cardiomyopathy, congestive heart failure with permanent sequelae, clinically significant arrhythmia (including any arrhythmia requiring medication, treatment, or clinical follow-up)
• Chronic active hepatitis B or active hepatitis C (for example, positive serology with confirmatory positive polymerase chain reaction) or active syphilis infection. Active syphilis documented by examination or serology unless positive serology is due to past treated infection
• Receipt of blood products or immunoglobulin in the past 3 months
• History of anaphylaxis or other serious adverse reactions to vaccines or vaccine products, or neomycin or streptomycin or egg products
• History of chronic urticaria (recurrent hives)

Sponsors & Collaborators

• Janssen Vaccines & Prevention B.V.: lead

Study Sites (1)

Unknown Facility

Bangkok, Thailand

Location

Related Publications (2)

• Kroon E, Chottanapund S, Buranapraditkun S, Sacdalan C, Colby DJ, Chomchey N, Prueksakaew P, Pinyakorn S, Trichavaroj R, Vasan S, Manasnayakorn S, Reilly C, Helgeson E, Anderson J, David C, Zulk J, de Souza M, Tovanabutra S, Schuetz A, Robb ML, Douek DC, Phanuphak N, Haase A, Ananworanich J, Schacker TW. Paradoxically Greater Persistence of HIV RNA-Positive Cells in Lymphoid Tissue When ART Is Initiated in the Earliest Stage of Infection. J Infect Dis. 2022 Jun 15;225(12):2167-2175. doi: 10.1093/infdis/jiac089.

  PMID: 35275599 DERIVED

• Colby DJ, Sarnecki M, Barouch DH, Tipsuk S, Stieh DJ, Kroon E, Schuetz A, Intasan J, Sacdalan C, Pinyakorn S, Grandin P, Song H, Tovanabutra S, Shubin Z, Kim D, Paquin-Proulx D, Eller MA, Thomas R, de Souza M, Wieczorek L, Polonis VR, Pagliuzza A, Chomont N, Peter L, Nkolola JP, Vingerhoets J, Truyers C, Pau MG, Schuitemaker H, Phanuphak N, Michael N, Robb ML, Tomaka FL, Ananworanich J. Safety and immunogenicity of Ad26 and MVA vaccines in acutely treated HIV and effect on viral rebound after antiretroviral therapy interruption. Nat Med. 2020 Apr;26(4):498-501. doi: 10.1038/s41591-020-0774-y. Epub 2020 Mar 23.

  PMID: 32235883 DERIVED

Related Links

• Manual upload due to format issue between PRS and PCM.

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

Subgroup analyses were performed by Ad26 baseline seropositivity for the humoral (ie, binding antibody responses; Env ELISA IgG-t gp140) and cellular immune responses (ie, IFN T cell responses and epitope mapping), and by time to rebound (3 tertile subgroups) for both the humoral and cellular immune responses (all parameters). Due to the low number of participants in each subgroup, no firm conclusions could be made.

Results Point of Contact

• Title: CLINICAL FRANCHISE LEADER
• Organization: Janssen Vaccines and Prevention BV

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Vaccines & Prevention B.V. Clinical Trial

  Janssen Vaccines & Prevention B.V.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2016
• First Posted: September 29, 2016
• Study Start: September 1, 2016
• Primary Completion: September 1, 2018
• Study Completion: September 1, 2018
• Last Updated: February 4, 2025
• Results First Posted: March 11, 2022

Record last verified: 2025-01

Locations

TH (1)