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| ID | Type | Description | Link |
|---|---|---|---|
| 2004_091 |
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| Name | Class |
|---|---|
| HIV Vaccine Trials Network | NETWORK |
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This study will test the safety and efficacy of an investigational Human Immunodeficiency Virus (HIV) vaccine. Efficacy will be measured by either prevention of HIV infection or control of HIV viral load in subjects who become HIV infected.
On September 18, 2007 the Protocol V520-023 DSMB (Data & Safety Monitoring Board) reviewed data from a planned interim analysis. These data demonstrated that the investigational vaccine candidate was not effective, and all vaccinations in the study were halted.
Participants were encouraged to continue to come to the clinic for scheduled visits and ongoing risk reduction counseling since the vaccine was not effective.
No further treatment was given in V520-023, however participants were followed. V520-023 protocol ended earlier than originally planned per protocol and participants (HIV infected and uninfected) had the option of participating in an observational long term follow up protocol called V520-030/HVTN 504, which served as an extension of V520-023 and would continue through the end of 2009.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Trivalent MRKAd5 HIV-1 gag/pol/nef | Experimental | Participants randomized to receive three 1.0-ml intramuscular (IM) injections of Merck Trivalent Adenovirus Serotype 5 HIV-1 gag/pol/nef (MRKAd5 HIV-1 gag/pol/nef) Vaccine at a dose of 1.5x10^10 adenovirus genomes (Ad vg) per dose at Day 1, Week 4, and Week 26. |
|
| Placebo | Placebo Comparator | Participants randomized to receive three 1.0-ml intramuscular (IM) injections of placebo to MRKAd5 HIV-1 gag/pol/nef at Day 1, Week 4, and Week 26. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Trivalent MRKAd5 HIV-1 gag/pol/nef (1.5x10^10 ad-vg/dose) | Biological | Trivalent MRKAd5 HIV-1 gag/pol/nef (1.5x10^10 adenovirus genomes [ad-vg]/dose). This dose is equivalent to 3x10^10 vp/dose used in study V520-016. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Clinical Adverse Experiences | Number of participants with non-serious AEs with an incidence cut-off of 5% (>5% in at least one treatment group) and number of participants with >1 SAE following administration of study vaccine. AEs collected include serious and non-serious systemic AEs, and injection-site AEs. All systemic AEs were collected up to 14 days after any vaccine dose, and serious AEs were collected for the entire study period (up to Week 210). Injection-site AEs are any swelling, redness, pain or tenderness at the injection site. All injection site AEs were collected up to Day 4 after any vaccine dose. | Day 1 to End of Study (Week 210 for HIV uninfected participants and Week 338 for HIV infected participants) |
| Number of Participants With Laboratory Adverse Experiences | Number of participants with laboratory adverse experiences with an incidence cut-off of 5% (events occurring > 5% in at least one treatment group) following administration of the first dose of study vaccine. Laboratory AEs were based on a grading system considering the severity of abnormal laboratory values in participants and reflect any unfavorable and unintentional change in function, or chemistry of the body. All laboratory AEs were collected up to 14 days after any vaccine dose. | Day 1 to Week 208 |
| Number of Participants With HIV-1 Infections | The number of participants with HIV-1 infections was to be determined with a periodic HIV-1 screening test to detect antibodies to recombinant HIV-1 envelope protein in the participants' serum. | Day 1 to End of Study (Week 210 for HIV uninfected participants and Week 338 for HIV infected participants) |
| HIV-1 Viral Load in Infected Participants | Plasma HIV-1 viral RNA was to be measured using a ribonucleic acid polymerase chain reaction (RNA PCR) on the last archived sample, and at Weeks 1, 2, 8, 12, and 26 post-HIV-1 infection, and subsequently every 6 months. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor | Merck Sharp & Dohme LLC | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19012954 | Background | Buchbinder SP, Mehrotra DV, Duerr A, Fitzgerald DW, Mogg R, Li D, Gilbert PB, Lama JR, Marmor M, Del Rio C, McElrath MJ, Casimiro DR, Gottesdiener KM, Chodakewitz JA, Corey L, Robertson MN; Step Study Protocol Team. Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet. 2008 Nov 29;372(9653):1881-1893. doi: 10.1016/S0140-6736(08)61591-3. Epub 2008 Nov 13. | |
| 23878319 |
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3000 participants were enrolled and randomized in the study. However, only 2979 received study vaccination, and are included in the started population.
V520-023 was terminated early based on findings at a planned interim analysis and subjects were encouraged to participate in the V520-030 rollover study for additional long term follow up.
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| ID | Title | Description |
|---|---|---|
| FG000 | Trivalent MRKAd5 HIV-1 Gag/Pol/Nef | Participants randomized to receive three 1.0-ml intramuscular (IM) injections of Merck Trivalent Adenovirus Serotype 5 HIV-1 gag/pol/nef (MRKAd5 HIV-1 gag/pol/nef) Vaccine at a dose of 1.5x10^10 adenovirus genomes (Ad vg) per dose at Day 1, Week 4, and Week 26. |
| FG001 | Placebo | Participants randomized to receive three 1.0-ml intramuscular (IM) injections of placebo to MRKAd5 HIV-1 gag/pol/nef at Day 1, Week 4, and Week 26. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Trivalent MRKAd5 HIV-1 Gag/Pol/Nef | Participants randomized to receive three 1.0-ml intramuscular (IM) injections of Merck Trivalent Adenovirus Serotype 5 HIV-1 gag/pol/nef (MRKAd5 HIV-1 gag/pol/nef) Vaccine at a dose of 1.5x10^10 adenovirus genomes (Ad vg) per dose at Day 1, Week 4, and Week 26. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Clinical Adverse Experiences | Number of participants with non-serious AEs with an incidence cut-off of 5% (>5% in at least one treatment group) and number of participants with >1 SAE following administration of study vaccine. AEs collected include serious and non-serious systemic AEs, and injection-site AEs. All systemic AEs were collected up to 14 days after any vaccine dose, and serious AEs were collected for the entire study period (up to Week 210). Injection-site AEs are any swelling, redness, pain or tenderness at the injection site. All injection site AEs were collected up to Day 4 after any vaccine dose. | Posted | Number | Participants | Day 1 to End of Study (Week 210 for HIV uninfected participants and Week 338 for HIV infected participants) |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Trivalent MRKAd5 HIV-1 Gag/Pol/Nef | Participants randomized to receive three 1.0-ml intramuscular (IM) injections of Merck Trivalent Adenovirus Serotype 5 HIV-1 gag/pol/nef (MRKAd5 HIV-1 gag/pol/nef) Vaccine at a dose of 1.5x10^10 adenovirus genomes (Ad vg) per dose at Day 1, Week 4, and Week 26. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia aggravated | Blood and lymphatic system disorders |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders |
The DSMB (Data & Safety Monitoring Board) reviewed interim data which demonstrated that the investigational vaccine was not effective, and all vaccinations were halted. Long term follow up was available for participants in V520-030.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck, Sharp & Dohme | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D000163 | Acquired Immunodeficiency Syndrome |
| D015658 | HIV Infections |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
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|
| Comparator: placebo | Drug | Placebo to Trivalent MRKAd5 HIV-1 gag/pol/nef in three 1 mL doses at Day 1, Week 4, and Week 26 administered intramuscularly. |
|
| Day 1 to End of Study (Week 210 for HIV uninfected participants and Week 338 for HIV infected participants) |
| Derived |
| Janes H, Friedrich DP, Krambrink A, Smith RJ, Kallas EG, Horton H, Casimiro DR, Carrington M, Geraghty DE, Gilbert PB, McElrath MJ, Frahm N. Vaccine-induced gag-specific T cells are associated with reduced viremia after HIV-1 infection. J Infect Dis. 2013 Oct 15;208(8):1231-9. doi: 10.1093/infdis/jit322. Epub 2013 Jul 21. |
| 22561365 | Derived | Duerr A, Huang Y, Buchbinder S, Coombs RW, Sanchez J, del Rio C, Casapia M, Santiago S, Gilbert P, Corey L, Robertson MN; Step/HVTN 504 Study Team. Extended follow-up confirms early vaccine-enhanced risk of HIV acquisition and demonstrates waning effect over time among participants in a randomized trial of recombinant adenovirus HIV vaccine (Step Study). J Infect Dis. 2012 Jul 15;206(2):258-66. doi: 10.1093/infdis/jis342. Epub 2012 May 4. |
| 21860356 | Derived | Barnabas RV, Wasserheit JN, Huang Y, Janes H, Morrow R, Fuchs J, Mark KE, Casapia M, Mehrotra DV, Buchbinder SP, Corey L; NIAID HIV Vaccine Trials Network. Impact of herpes simplex virus type 2 on HIV-1 acquisition and progression in an HIV vaccine trial (the Step study). J Acquir Immune Defic Syndr. 2011 Jul 1;57(3):238-44. doi: 10.1097/QAI.0b013e31821acb5. |
| 21343146 | Derived | Fitzgerald DW, Janes H, Robertson M, Coombs R, Frank I, Gilbert P, Loufty M, Mehrotra D, Duerr A; Step Study Protocol Team. An Ad5-vectored HIV-1 vaccine elicits cell-mediated immunity but does not affect disease progression in HIV-1-infected male subjects: results from a randomized placebo-controlled trial (the Step study). J Infect Dis. 2011 Mar 15;203(6):765-72. doi: 10.1093/infdis/jiq114. |
| Protocol Violation |
|
| Withdrawal by Subject |
|
| Option to switch to a rollover study |
|
| Site terminated |
|
| Subject moved |
|
| Placebo |
Participants randomized to receive three 1.0-ml intramuscular (IM) injections of placebo to MRKAd5 HIV-1 gag/pol/nef at Day 1, Week 4, and Week 26. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG001 | Placebo | Participants randomized to receive three 1.0-ml intramuscular (IM) injections of placebo to MRKAd5 HIV-1 gag/pol/nef at Day 1, Week 4, and Week 26. |
|
|
| Primary | Number of Participants With Laboratory Adverse Experiences | Number of participants with laboratory adverse experiences with an incidence cut-off of 5% (events occurring > 5% in at least one treatment group) following administration of the first dose of study vaccine. Laboratory AEs were based on a grading system considering the severity of abnormal laboratory values in participants and reflect any unfavorable and unintentional change in function, or chemistry of the body. All laboratory AEs were collected up to 14 days after any vaccine dose. | Posted | Number | Participants | Day 1 to Week 208 |
|
|
|
| Primary | Number of Participants With HIV-1 Infections | The number of participants with HIV-1 infections was to be determined with a periodic HIV-1 screening test to detect antibodies to recombinant HIV-1 envelope protein in the participants' serum. | An interim analysis for this study showed that the MRK Ad5 HIV-1 gag/pol/nef vaccine used in this study was not efficacious; therefore, this outcome measure was not analyzed and only a high level summary of the safety data was performed. | Posted | Day 1 to End of Study (Week 210 for HIV uninfected participants and Week 338 for HIV infected participants) |
|
|
| Primary | HIV-1 Viral Load in Infected Participants | Plasma HIV-1 viral RNA was to be measured using a ribonucleic acid polymerase chain reaction (RNA PCR) on the last archived sample, and at Weeks 1, 2, 8, 12, and 26 post-HIV-1 infection, and subsequently every 6 months. | An interim analysis for this study showed that the MRK Ad5 HIV-1 gag/pol/nef vaccine used in this study was not efficacious; therefore, this outcome measure was not analyzed and only a high level summary of the safety data was performed. | Posted | Day 1 to End of Study (Week 210 for HIV uninfected participants and Week 338 for HIV infected participants) |
|
|
| 19 |
| 1,484 |
| 1,221 |
| 1,484 |
| EG001 | Placebo | Participants randomized to receive three 1.0-ml intramuscular (IM) injections of placebo to MRKAd5 HIV-1 gag/pol/nef at Day 1, Week 4, and Week 26. | 17 | 1,495 | 946 | 1,495 |
| Congenital cardiovascular anomaly | Congenital, familial and genetic disorders |
|
| Hypoplastic left heart syndrome | Congenital, familial and genetic disorders |
|
| Unspecified congenital anomaly of heart | Congenital, familial and genetic disorders |
|
| Ventricular septal defect | Congenital, familial and genetic disorders |
|
| Acute diarrhoea | Gastrointestinal disorders |
|
| Fever | General disorders |
|
| Rigors | General disorders |
|
| Cholecystitis acute | Hepatobiliary disorders |
|
| Drug hypersensitivity | Immune system disorders |
|
| Appendicitis | Infections and infestations |
|
| Gastroenteritis viral | Infections and infestations |
|
| Pulmonary tuberculosis | Infections and infestations |
|
| Shunt infection | Infections and infestations |
|
| Staphylococcal abscess | Infections and infestations |
|
| Vulval abscess | Infections and infestations |
|
| Asbestosis | Injury, poisoning and procedural complications |
|
| Gun shot wound | Injury, poisoning and procedural complications |
|
| Overdose | Injury, poisoning and procedural complications |
|
| Stab wound | Injury, poisoning and procedural complications |
|
| Traumatic brain injury | Injury, poisoning and procedural complications |
|
| Dehydration | Metabolism and nutrition disorders |
|
| Low back pain | Musculoskeletal and connective tissue disorders |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders |
|
| Slipped disc | Musculoskeletal and connective tissue disorders |
|
| Gastric cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| Uterine fibroids | Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| Headache | Nervous system disorders |
|
| Depression | Psychiatric disorders |
|
| Depression aggravated | Psychiatric disorders |
|
| Depressive episode | Psychiatric disorders |
|
| Manic episode | Psychiatric disorders |
|
| Polysubstance dependence | Psychiatric disorders |
|
| Substance abuse | Psychiatric disorders |
|
| Suicide attempt | Psychiatric disorders |
|
| Kidney stone | Renal and urinary disorders |
|
| Exacerbation of asthma | Respiratory, thoracic and mediastinal disorders |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders |
|
| Respiratory distress | Respiratory, thoracic and mediastinal disorders |
|
| Hypertension | Vascular disorders |
|
| Nausea | Gastrointestinal disorders |
|
| Fatigue | General disorders |
|
| Fever | General disorders |
|
| General body pain | General disorders |
|
| Injection site erythema | General disorders |
|
| Injection site pain | General disorders |
|
| Injection site swelling | General disorders |
|
| Injection site tenderness | General disorders |
|
| Headache | Nervous system disorders |
|
| Sore throat | Respiratory, thoracic and mediastinal disorders |
|
As this study is part of a multicenter trial, publications derived from this study should include input from the principal investigator, his/her colleagues, the other investigators in this trial, and SPONSOR personnel.
The SPONSOR must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. SPONSOR review can be expedited to meet publication guidelines.
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D012897 | Slow Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |