Clinical trial NCT02919306: Safety and Efficacy Study of Vaccine Schedule With Ad26.Mos.HIV and MVA-Mosaic in Human Immunodeficiency Virus (HIV)-Infected Adults
Official title: A Combined Phase 1/2a, Exploratory Study of a Therapeutic Vaccine Using an Adenovirus Type 26 Vector Prime and Modified Vaccinia Ankara Boost Combination With Mosaic Inserts in HIV-1 Infected Adults Who Initiated Antiretroviral Treatment During Acute HIV Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Human Immunodeficiency Virus
Lead sponsor: Janssen Vaccines & Prevention B.V.
Sponsor class: INDUSTRY
First posted: 2016-09-29
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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)
* Chronic or recurrent use of medications which modify host immune response, example (e.g.) cancer chemotherapeutic agents, parenteral corticosteroids (short course oral steroids given for non-chronic conditions not expected to recur is not an exclusion criteria, topical steroid use is not an exclusion criteria), etc. but not including ART

Primary outcomes:
measure: Percentage of Participants With Grade 3 or 4 Solicited Local Adverse Events (AEs)
timeFrame: Up to Week 49 (7 days post each vaccination)
measure: Percentage of Participants With Grade 3 or 4 Solicited Systemic AEs
timeFrame: Up to Week 49 (7 days post each vaccination)
measure: Percentage of Participants With Grade 3 or 4 Unsolicited AEs
timeFrame: Up to Week 52 (28 days after each vaccination)
measure: Percentage of Participants With Grade 3 or 4 Related AEs
timeFrame: Up to Week 52 (28 days after each vaccination)
measure: Percentage of Participants With Solicited Local AEs for 7 Days After Each Vaccination
timeFrame: Up to Week 49 (7 days post each vaccination)
measure: Percentage of Participants With Solicited Systemic AEs for 7 Days After Each Vaccination
timeFrame: Up to Week 49 (7 days after each vaccination)
measure: Percentage of Participants With Unsolicited AEs 28 Days After Each Vaccination
timeFrame: Up to Week 52 (28 days after each vaccination)
measure: Percentage of Participants With Related AEs and Serious Adverse Events (SAEs)
timeFrame: Up to Week 52 (28 days after each vaccination)
measure: Percentage of Participants With AEs Leading to Discontinuation of Study Vaccination
timeFrame: Up to Week 96
measure: Percentage of Participants With AEs
timeFrame: Up to Week 52 (28 days after each vaccination)
measure: Percentage of Participants With Worst Laboratory Toxicity Grades 1, 2, 3, and 4 and Non-graded Serum Chemistry Abnormalities
timeFrame: Up to Week 96
measure: Percentage of Participants With Worst Laboratory Toxicity Grade 1 and Non-graded Hematology Abnormalities
timeFrame: Up to Week 96
measure: 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
timeFrame: From Week 60 to Week 96
measure: Duration of Sustained Viremic Control With HIV RNA <50 Copies/mL During ATI Phase
timeFrame: From Week 60 to Week 96
Secondary outcomes:
measure: Total HIV Deoxyribonucleic Acid (DNA) Levels Over Time
timeFrame: From Week 60 to Week 96
measure: Change in Cluster of Differentiation (CD)4 Count Over Time
timeFrame: Baseline and from Week 60 to Week 96
measure: Time to Reinitiating ART
timeFrame: Up to Week 96
measure: Number of Participants With Acute Retroviral Syndrome Post-ARV ATI
timeFrame: From Week 60 to Week 96
measure: Duration of Acute Retroviral Syndrome Post-ARV ATI
timeFrame: From Week 60 to Week 96
measure: Percentage of Participants With HIV Resistance to ARV Drugs Who Experienced Rebound Viremia After ARV ATI
timeFrame: From Week 60 to Week 96
measure: Percentage of Responders With Interferon-gamma (IFN-gamma) T Cell Responses Analyzed by Enzyme-linked Immunospot Assay (ELISpot) at Week 24, 26, 48, and 50
timeFrame: At Week 24, 26, 48 and 50
measure: Percentage of Responders for Envelop (Env) Clade A, B, C and Mos1-specific Binding Antibody Titers
timeFrame: At Week 24, 26, 48 and 50
measure: Percentage of Responders for Clade C (C97ZA.012) Env ELISA Immunoglobulin G1 (IgG1), IgG2, and IgG3 Glycoprotein (gp) 140 Binding Antibody
timeFrame: Week 50
measure: Breadth of T Cell Responses Analyzed by ELISPOT Assays
timeFrame: Baseline (Week 0), Week 26 and 50
measure: Percentage of Env Antibody-dependent Cellular Phagocytosis (ADCP) Glycoprotein (gp) Antibody Over Time
timeFrame: At Week 24, 26, 48 and 50
measure: Percentage of Responders for HIV Neutralizing Antibody (nAb)
timeFrame: Week 64
Other outcomes:
Locations:
city: Bangkok
country: Thailand
Study officials:
affiliation: Janssen Vaccines & Prevention B.V.
name: Janssen Vaccines & Prevention B.V. Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.