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| ID | Type | Description | Link |
|---|---|---|---|
| 2013-004747-23 | EudraCT Number |
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| Name | Class |
|---|---|
| Celgene Corporation | INDUSTRY |
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The REDUC trial's objective is to address one of the core issues with the treatment of HIV, which is that some HIV infected cells hide in so-called latent reservoirs. The reservoirs are unaffected by conventional HIV medication and invisible to the immune system. HDACi have the potential to activate these latently infected cells. This will make the HIV infected cells visible to the immune system; the immune response generate by Vacc-4x will be able to attack and eliminate the infected cells.
The study is divide into two parts. In Part A the safety and tolerability of romidepsin will be evaluated and the effect of romidepsin treatment on HIV-1 transcription in HIV-infected patients virologically suppressed on cART will be determined.
In Part B the effect of treatment with Vacc-4x + rhuGM-CSF and romidepsin treatment on the HIV-1 latent reservoir in HIV-infected patients virologically suppressed on cART will be measured.
Six patients will be enrolled for part A and the safety and tolerability profile evaluated before enrolling 20 patients in B.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A | Other | Pre-treatment phase of 2-4 weeks (Visit 1- Visit 2a) followed by viral reactivation phase of 3 weeks (Visit 2 to Visit 7) consisting of one cycle of romidepsin infusions at a dosing of 5 mg/m2 on days 0, 7, and 14. Post-activation phase of ~9 weeks (Visit 8 to Visit 11) to assess the effect of romidepsin on the size of latent HIV-1 reservoir. |
|
| Part B | Other | Pre-treatment phase of 2-4 weeks (Visit 1-Visit 2) followed by a therapeutic HIV-1 immunization phase of 12 weeks (Visit 2 to Visit 7) in which 1.2 mg Vacc-4x was administered together with 0.06 mg rhuGM-CSF at Visits 2, 3, 4, 5, 6 and 7 follow by a follow-up period of 2 weeks (Visit 8). A viral reactivation phase of 3 weeks (Visit 9-Visit 11) consisting of one cycle of 3 romidepsin infusions (5 mg/m2) followed by a post-treatment observation phase of ~9 weeks (Visit 12-Visit 13) to assess the effect of the investigational treatment on the size of the latent HIV-1 reservoir. A monitored antiretroviral pause of up to 16 weeks (Visit 14-Visit 33). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Romidepsin | Drug | Latency reversing agent |
|
| Measure | Description | Time Frame |
|---|---|---|
| Part A: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | Safety and tolerability evaluation as measured by adverse events (AE) and serious adverse events (SAE). | 3 weeks |
| Part B: Changes From Baseline in HIV-1 Reservoir (Total HIV-1DNA; Integrated HIV-1 DNA in Unfractionated CD4+ T Cells and Replication Competent Provirus. | Total HIV-1 DNA and integrated HIV-1 DNA were analysed by MMRM analysis (copies/10^6 CD4+ T cells). To estimate the frequency of infectious units per 10^6 resting memory CD4+ T cells a quantitative viral outgrowth assay (qVOA) was used. Blood samples were obtained at Day 0, Day 105 and Day 161. | Day 161/175 |
| Measure | Description | Time Frame |
|---|---|---|
| Part A: Changes From Baseline in HIV-1 Reservoir (Total HIV-1DNA; Integrated HIV-1 DNA in Unfractionated CD4+ T Cells and Replication Competent Provirus. Estimates of Change From Baseline of the Size of the Latent HIV-1 Reservoir in CD4+ Cells. | Total HIV-1 DNA and integrated HIV-1 DNA were analysed by MMRM analysis (copies/10^6 CD4+ T cells). To estimate the frequency of infectious units per 10^6 resting memory CD4+ T cells a quantitative viral outgrowth assay (qVOA) was used. Total HIV-1 DNA was measured at Day 84 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Lars Jørgen Østergaard, MD, PhD | Aarhus University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Aarhus University Hospital, Skejby Sygehus | Aarhus N | 8200 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27658863 | Derived | Leth S, Schleimann MH, Nissen SK, Hojen JF, Olesen R, Graversen ME, Jorgensen S, Kjaer AS, Denton PW, Mork A, Sommerfelt MA, Krogsgaard K, Ostergaard L, Rasmussen TA, Tolstrup M, Sogaard OS. Combined effect of Vacc-4x, recombinant human granulocyte macrophage colony-stimulating factor vaccination, and romidepsin on the HIV-1 reservoir (REDUC): a single-arm, phase 1B/2A trial. Lancet HIV. 2016 Oct;3(10):e463-72. doi: 10.1016/S2352-3018(16)30055-8. Epub 2016 Jul 7. | |
| 26379282 |
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Participants have not provided informed consent for their anonymized individual data to be made available beyond that described in the patient information sheet.
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7 patients were screened and 6 patients were enrolled in Part A. 24 patients were screened and 20 patients were enrolled in Part B.
First subject screened 6 March 2014 and last subject last visit 25 June 2014 for Part A.
First subject screened 19 May 2014 and last subject last visit 29 May 2015 for Part B.
One clinical trial site at Aarhus University Hospital, Denmark
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| ID | Title | Description |
|---|---|---|
| FG000 | Part A | Pre-treatment phase of 2-4 weeks (Visit 1- Visit 2a) followed by viral reactivation phase of 3 weeks (Visit 2 to Visit 7) consisting of one cycle of romidepsin infusions at a dosing of 5 mg/m2 on days 0, 7, and 14. Post-activation phase of ~9 weeks (Visit 8 to Visit 11) to assess the effect of romidepsin on the size of latent HIV-1 reservoir. |
| FG001 | Part B | Pre-treatment phase of 2-4 weeks (Visit 1-Visit 2) followed by a therapeutic HIV-1 immunization phase of 12 weeks (Visit 2 to Visit 7) in which 1.2 mg Vacc-4x was administered together with 0.06 mg rhuGM-CSF at Visits 2, 3, 4, 5, 6 and 7 follow by a follow-up period of 2 weeks (Visit 8). A viral reactivation phase of 3 weeks (Visit 9-Visit 11) consisting of one cycle of 3 romidepsin infusions (5 mg/m2) followed by a post-treatment observation phase of ~9 weeks (Visit 12-Visit 13) to assess the effect of the investigational treatment on the size of the latent HIV-1 reservoir. A monitored antiretroviral pause of up to 16 weeks (Visit 14-Visit 33). |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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|
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| ID | Title | Description |
|---|---|---|
| BG000 | Part A | Pre-treatment phase of 2-4 weeks (Visit 1- Visit 2a) followed by viral reactivation phase of 3 weeks (Visit 2 to Visit 7) consisting of one cycle of romidepsin infusions at a dosing of 5 mg/m2 on days 0, 7, and 14. Post-activation phase of ~9 weeks (Visit 8 to Visit 11) to assess the effect of romidepsin on the size of latent HIV-1 reservoir. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Number |
| 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 | Part A: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | Safety and tolerability evaluation as measured by adverse events (AE) and serious adverse events (SAE). | Posted | Number | participants | 3 weeks |
|
|
Adverse events were collected from first treatment (Day 0) to the last visit (day 11 for Part A and day 287 for part B). Any signs or symptoms occurring between Screening/Visit 1 and Visit 2 (day 0)was recorded as Medical History.
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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 | Part A | Pre-treatment phase of 2-4 weeks (Visit 1- Visit 2a) followed by viral reactivation phase of 3 weeks (Visit 2 to Visit 7) consisting of one cycle of romidepsin infusions at a dosing of 5 mg/m2 on days 0, 7, and 14. Post-activation phase of ~9 weeks (Visit 8 to Visit 11) to assess the effect of romidepsin on the size of latent HIV-1 reservoir. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Alcohol withdrawal syndrome | Psychiatric disorders | MedDRA (17.0) | Systematic Assessment | One subject (01-225) presented three SAEs; all three were described as "alcohol withdrawal syndrome" and assessed as not related to Vacc-4x and GM-CSF and romidepsin |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Maja Sommerfelt | Bionor Pharma ASA | +4723010960 | ms@bionorpharma.com |
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| ID | Term |
|---|---|
| C087123 | romidepsin |
| C494182 | Vacc-4x |
| C081222 | sargramostim |
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| Vacc-4x | Biological | Vacc-4x is a peptide-based HIV immunotherapy administered intradermally. Vacc-4x peptides are reconstituted in sterile water. |
|
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| rhuGM-CSF | Biological | Granulocyte macrophage colony stimulating factor as a local adjuvant |
|
|
| Day 56/84 |
| Part B: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | Safety and tolerability evaluation of romidepsin and Vacc-4x in combination with GM-CSF as measured by adverse events (AE) and serious adverse events (SAE). | 287 days |
| Part B: Level of HIV-1 Transcription. | At day 105, 112 and 119 patients receive romidepsin and 4 hours after each administration HIV transcription is measured as unspliced HIV-1 RNA. | Day 105, 112 and 119 |
| Derived |
| Sogaard OS, Graversen ME, Leth S, Olesen R, Brinkmann CR, Nissen SK, Kjaer AS, Schleimann MH, Denton PW, Hey-Cunningham WJ, Koelsch KK, Pantaleo G, Krogsgaard K, Sommerfelt M, Fromentin R, Chomont N, Rasmussen TA, Ostergaard L, Tolstrup M. The Depsipeptide Romidepsin Reverses HIV-1 Latency In Vivo. PLoS Pathog. 2015 Sep 17;11(9):e1005142. doi: 10.1371/journal.ppat.1005142. eCollection 2015 Sep. |
| BG001 |
| Part B |
Pre-treatment phase of 2-4 weeks (Visit 1-Visit 2) followed by a therapeutic HIV-1 immunization phase of 12 weeks (Visit 2 to Visit 7) in which 1.2 mg Vacc-4x was administered together with 0.06 mg rhuGM-CSF at Visits 2, 3, 4, 5, 6 and 7 follow by a follow-up period of 2 weeks (Visit 8). A viral reactivation phase of 3 weeks (Visit 9-Visit 11) consisting of one cycle of 3 romidepsin infusions (5 mg/m2) followed by a post-treatment observation phase of ~9 weeks (Visit 12-Visit 13) to assess the effect of the investigational treatment on the size of the latent HIV-1 reservoir. A monitored antiretroviral pause of up to 16 weeks (Visit 14-Visit 33). |
| BG002 | Total | Total of all reporting groups |
| participants |
|
| Gender | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
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| Time since HIV diagnosis | Median | Full Range | years |
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| Time since HIV infection | Information was not available for 2 patients in Part A and for 1 patient in Part B. | Median | Full Range | years |
|
| Time since ART initiation | Median | Full Range | years |
|
| Latest pre-ART viral load | Pre-ART viral load was not availabel for 2 patrients in Part B. | Median | Full Range | copies/mL |
|
| Nadir CD4+ T-cell count | Median | Full Range | 10^6 cells/L |
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| Mean CD4+ T-cell counts | Median | Full Range | 10^6 cells/L |
|
| Participants |
|
|
| Primary | Part B: Changes From Baseline in HIV-1 Reservoir (Total HIV-1DNA; Integrated HIV-1 DNA in Unfractionated CD4+ T Cells and Replication Competent Provirus. | Total HIV-1 DNA and integrated HIV-1 DNA were analysed by MMRM analysis (copies/10^6 CD4+ T cells). To estimate the frequency of infectious units per 10^6 resting memory CD4+ T cells a quantitative viral outgrowth assay (qVOA) was used. Blood samples were obtained at Day 0, Day 105 and Day 161. | 4 patients were excluded; 3 discontinued and 1 sample was not eligible for analysis. Sensitivity of the qVOA was low; 2/3 of all measurements were under the limit of detection. 6 subjects had quantifiable viral outgrowth on baseline, 8 had viral outgrowth after immunization (Day 105) and 6 had viral outgrowth after romidepsin (Day 161). | Posted | Mean | 95% Confidence Interval | Estimated % change from baseline | Day 161/175 |
|
|
|
| Secondary | Part A: Changes From Baseline in HIV-1 Reservoir (Total HIV-1DNA; Integrated HIV-1 DNA in Unfractionated CD4+ T Cells and Replication Competent Provirus. Estimates of Change From Baseline of the Size of the Latent HIV-1 Reservoir in CD4+ Cells. | Total HIV-1 DNA and integrated HIV-1 DNA were analysed by MMRM analysis (copies/10^6 CD4+ T cells). To estimate the frequency of infectious units per 10^6 resting memory CD4+ T cells a quantitative viral outgrowth assay (qVOA) was used. Total HIV-1 DNA was measured at Day 84 | 1 patient did not have a quantifiable load of total HIV-1 DNA at Day 84 and 2 patients diod not have a quantifiable load of replication competent provirus at day 56. | Posted | Mean | Standard Deviation | copies/10^6 CD4+ T cells | Day 56/84 |
|
|
|
| Secondary | Part B: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | Safety and tolerability evaluation of romidepsin and Vacc-4x in combination with GM-CSF as measured by adverse events (AE) and serious adverse events (SAE). | Posted | Number | participants | 287 days |
|
|
|
| Secondary | Part B: Level of HIV-1 Transcription. | At day 105, 112 and 119 patients receive romidepsin and 4 hours after each administration HIV transcription is measured as unspliced HIV-1 RNA. | All available samples were included in this analysis; 3 withdrew consent and 2 (3 for day 119) did not have analyzable samples. | Posted | Mean | Standard Deviation | copies/10^6 CD4+ T cells | Day 105, 112 and 119 |
|
|
|
| 0 |
| 6 |
| 6 |
| 6 |
| EG001 | Part B | Pre-treatment phase of 2-4 weeks (Visit 1-Visit 2) followed by a therapeutic HIV-1 immunization phase of 12 weeks (Visit 2 to Visit 7) in which 1.2 mg Vacc-4x was administered together with 0.06 mg rhuGM-CSF at Visits 2, 3, 4, 5, 6 and 7 follow by a follow-up period of 2 weeks (Visit 8). A viral reactivation phase of 3 weeks (Visit 9-Visit 11) consisting of one cycle of romidepsin infusion (5 mg/m2) followed by a post-treatment observation phase of ~9 weeks (Visit 12-Visit 13) to assess the effect of the investigational treatment on the size of the latent HIV-1 reservoir. A monitored antiretroviral pause of up to 16 weeks (Visit 14-Visit 33). | 1 | 20 | 20 | 20 |
|
| Gastrointestinal sounds abnormal | General disorders | MedDRA (17.0) | Systematic Assessment |
|
| Abdominal Pain upper | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
|
| Gastrointestinal pain | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
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| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
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| Fatigue | General disorders | MedDRA (17.0) | Systematic Assessment |
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| Asthenia | General disorders | MedDRA (17.0) | Systematic Assessment |
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| Chills | General disorders | MedDRA (17.0) | Systematic Assessment |
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| Influenza like illness | General disorders | MedDRA (17.0) | Systematic Assessment |
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| Malaise | General disorders | MedDRA (17.0) | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA (17.0) | Systematic Assessment |
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| Burning sensation | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
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| Head Discomfort | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
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| Parosmia | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
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| Palpitations | Cardiac disorders | MedDRA (17.0) | Systematic Assessment |
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| Wrist Fracture | Injury, poisoning and procedural complications | MedDRA (17.0) | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA (17.0) | Systematic Assessment |
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| Injection site Pruritus | General disorders | MedDRA (17.0) | Systematic Assessment |
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| Injection site erythema | General disorders | MedDRA (17.0) | Systematic Assessment |
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| Injection site pain | General disorders | MedDRA (17.0) | Systematic Assessment |
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| Feeling hot | General disorders | MedDRA (17.0) | Systematic Assessment |
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| Injection site reaction | General disorders | MedDRA (17.0) | Systematic Assessment |
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| Vomitting | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
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| Colitis ulcerative | General disorders | MedDRA (17.0) | Systematic Assessment |
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| Fungal infection | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
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| Parynchia | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
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| Sinusitis | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
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| Petit mal epilepsy | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
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| Sensory disturbance | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (17.0) | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (17.0) | Systematic Assessment |
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| Photosensitivity reaction | Skin and subcutaneous tissue disorders | MedDRA (17.0) | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (17.0) | Systematic Assessment |
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| Bone fissure | Injury, poisoning and procedural complications | MedDRA (17.0) | Systematic Assessment |
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| Wound | Injury, poisoning and procedural complications | MedDRA (17.0) | Systematic Assessment |
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| Serum ferritin descreased | Investigations | MedDRA (17.0) | Systematic Assessment |
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| Viral load increased | Investigations | MedDRA (17.0) | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (17.0) | Systematic Assessment |
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| Pollakiuria | Renal and urinary disorders | MedDRA (17.0) | Systematic Assessment |
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| Urethral discharge | Renal and urinary disorders | MedDRA (17.0) | Systematic Assessment |
|
| Lymphadenitis | Blood and lymphatic system disorders | MedDRA (17.0) | Systematic Assessment |
|
| Tinnitus | Ear and labyrinth disorders | MedDRA (17.0) | Systematic Assessment |
|
| Wisdom teeth removal | Surgical and medical procedures | MedDRA (17.0) | Systematic Assessment |
|
The Sponsor (or designee) will prepare a final report on the study. The Investigator may not publish or present any information on this study without the express written approval of the Sponsor. Additionally, the Sponsor, may, for any reason, withhold approval for publication or presentation.
| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Replication competent provirus, day 161 |
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| Integrated HIV-1 DNA, Baseline |
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| Integrated HIV-1 DNA, Day 84 |
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| Replication competent provirus, Baseline |
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| Replication competent provirus, Day 56 |
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| Title | Measurements |
|---|---|
|
| Adverse reaction, grade 1 |
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| Adverse reaction, grade 2 |
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| Adverse reaction, grade 3 |
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| Related to Vacc-4x and GM-CSF |
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| Related to Romidepsin |
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| Not related |
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| Day 112, 4 hours post romidepsin |
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| Day 119, 4 hours post romidepsin |
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