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Safety, Tolerability and Immunogenicity Induced by the THV01 Treatment in Patients Infected With HIV-1 Clade B and Treated With Highly Active Antiretroviral Therapy (HAART).

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ClinicalTrials.gov Identifier: NCT02054286
Recruitment Status : Active, not recruiting
First Posted : February 4, 2014
Last Update Posted : October 18, 2018
Sponsor:
Information provided by (Responsible Party):
Theravectys S.A.

Brief Summary:

The objectives of this Phase I/II trial is to evaluate the safety, tolerability and immunogenicity of THV01 compared to placebo in HIV-1 infected patients on HAART (highly active antiretroviral therapies).

THV01 is composed of two vaccines that derived from the HIV (human immunodeficiency virus): lentiviral vectors. They are non-replicative and not infectious. They will be injected intramuscularly, eight weeks apart. Three doses will be assessed and compared to placebo.

Eligible patients must have an undetectable viral load and must be treated by HAART for more than 12 months. They will be randomly allocated to one of the study group and will receive the experimental drugs at one of the three doses or a matching placebo.

Their anti-HIV treatment will be alleviated around each experimental drugs' administration to enable THV01 efficacy. HAART will be resumed one week after the second injection. 15 weeks after resumption, HAART will be interrupted. Patients will then be monitored every 2 weeks for CD4+ T cell counts and viral load as well as for thorough assessment of the elicited immune response. Stringent anti-HIV treatments resumption criteria have been implemented, based on the CD4+ T cell counts and the viral load.

38 patients were enrolled in THV01-11-01 study and received the 2 injections.

A long-term follow-up of all enrolled patients will be performed for 5 years post-prime administration. This will provide additional data on the safety and the potential long-term risks/benefits associated with THV01.

The final study report will be written after the last patient last visit in the long-term follow-up.


Condition or disease Intervention/treatment Phase
HIV Infection Biological: THV01-1 Biological: THV01-2 Biological: Placebo Phase 1 Phase 2

Detailed Description:

This Phase I/II is a randomized, double-blind and placebo controlled study to assess safety, tolerability and immunogenicity of THV01 at three doses in patients infected with the HIV-1 clade B currently on HAART (highly active antiretroviral therapies).

THV01 involves two intramuscular injections, consisting of the THV01-1 and THV01-2 lentiviral vectors, to be administered intramuscularly eight weeks apart. These lentiviral vectors are non-replicative and self-inactivating. Both encode the same HIV antigen.

36 patients were planned to be enrolled. They must be HIV-1 (clade B) infected patients, treated by HAART for more than 12 months and with an undetectable viral load.

Patients will be randomly allocated to one of the groups:

  • Group 1: patients will receive the THV01-1 and THV01-2 vaccines at 5.10E+6 TU (transducing unit) or placebo;
  • Group 2: patients will receive the THV01-1 and THV01-2 vaccines at 5.10E+7 TU (transducing unit) or placebo;
  • Group 3: patients will receive the THV01-1 and THV01-2 vaccines at 5.10E+8 TU (transducing unit) or placebo.

Hence, twelve patients will be randomized in blocks of 4 in a 3:1 ratio (vaccine:placebo) for each dose.

Experimental drugs' injection will occur at Week 0 and Week 8. HAART will be alleviated for all patients during this "vaccination phase" to enable efficient transduction of the host cells by the lentiviral vectors. Initial HAART will be resumed at Week 9.

Starting on Week 24, HAART will be interrupted. Patients will then be monitored on a very stringent rhythm. HAART resumption criteria based on the CD4+ T cell counts and the viral load have been implemented to guaranty safety of all enrolled patients.

38 patients were enrolled in THV01-11-01 study and received the 2 injections.

A long-term follow-up of all enrolled patients will be performed for 5 years after the administration of THV01-1. During this follow-up, three visits are planned per year, during which blood will be sampled. This will provide data on the long-term safety of THV01 and the potential long-term risks/benefits associated with THV01.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 38 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multi-center, Randomized, Double-blind, Placebo-controlled Phase I/II Trial to Compare the Safety, Tolerability and Immunogenicity of the Therapeutic THV01 Vaccination at 5.10E+6 TU (Transducing Unit) , 5.10E+7 TU (Transducing Unit) or 5.10E+8 TU (Transducing Unit) Doses to Placebo in HIV-1 Clade B Infected Patients Under Highly Active Antiretroviral Therapy (HAART)
Actual Study Start Date : December 2012
Actual Primary Completion Date : August 2014
Estimated Study Completion Date : March 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Group 1: THV01 (5.10E+6 TU) or Placebo
5.10E+6 TU (transducing unit) of THV01-1 (Week 0) OR matching placebo; 5.10E+6 TU (transducing unit) of THV01-2 (Week 8) OR matching placebo
Biological: THV01-1
Intramuscular injection of THV01-1 (week 0)
Other Name: lentiviral vector ancoding an HIV antigen

Biological: THV01-2
Intramuscular injection of THV01-2 (week 8)
Other Name: lentiviral vector encoding an HIV antigen

Biological: Placebo
Intramuscular injection of placebo matching THV01-1 and THV01-2
Other Name: Placebo matching THV01-1 and THV01-2

Experimental: Group 2: THV01 (5.10E+7 TU) or Placebo
5.10E+7 TU (transducing unit) of THV01-1 (Week 0) OR matching placebo; 5.10E+7 TU (transducing unit) of THV01-2 (Week 8) OR matching placebo
Biological: THV01-1
Intramuscular injection of THV01-1 (week 0)
Other Name: lentiviral vector ancoding an HIV antigen

Biological: THV01-2
Intramuscular injection of THV01-2 (week 8)
Other Name: lentiviral vector encoding an HIV antigen

Biological: Placebo
Intramuscular injection of placebo matching THV01-1 and THV01-2
Other Name: Placebo matching THV01-1 and THV01-2

Experimental: Group 3: THV01 (5.10E+8 TU) or Placebo
5.10E+8 TU (transducing unit) of THV01-1 (Week 0) OR matching placebo; 5.10E+8 TU (transducing unit) of THV01-2 (Week 8) OR matching placebo
Biological: THV01-1
Intramuscular injection of THV01-1 (week 0)
Other Name: lentiviral vector ancoding an HIV antigen

Biological: THV01-2
Intramuscular injection of THV01-2 (week 8)
Other Name: lentiviral vector encoding an HIV antigen

Biological: Placebo
Intramuscular injection of placebo matching THV01-1 and THV01-2
Other Name: Placebo matching THV01-1 and THV01-2




Primary Outcome Measures :
  1. Safety and tolerability [ Time Frame: From Week 0 to Week 24 ]
    Occurrence of at least one grade 3 or higher adverse event including signs/symptoms, laboratory toxicities and/or clinical events possibly, probably or definitely related to study treatment.


Secondary Outcome Measures :
  1. Safety and tolerability [ Time Frame: From baseline to Week 88 (or early termination). ]
    Occurrence of at least one grade 3 or higher adverse event including signs/symptoms, laboratory toxicities and/or clinical events possibly, probably or definitely related to study treatment.

  2. Immunogenicity [ Time Frame: From baseline to Week 88 (or early termination). ]
    Monitoring the cellular immune response by treatment group versus placebo.


Other Outcome Measures:
  1. HIV reservoir (HIV total DNA) [ Time Frame: From baseline to five years after the prime injection. ]
    Evaluation of HIV reservoir by treatment group versus placebo.

  2. Long term safety [ Time Frame: From Week 88 to five years after the prime injection. ]
    Occurrence of any SAE (serious adverse event) suspected to be related to IMP.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria

  • Patients infected with clade B HIV-1;
  • Confirmation of a Gag clade B genotyping performed at screening;
  • Patient must be treated by a triple agents therapy for more than 12 months at baseline: this triple agents therapy should encompasses two (2) nucleosidic reverse transcriptase inhibitors plus one (1) boosted protease inhibitor, or two (2) nucleosidic reverse transcriptase inhibitors plus one (1) non nucleosidic reverse transcriptase inhibitor;
  • Patients must be treated for more than 60 days at baseline by two (2) nucleosidic reverse transcriptase inhibitors plus a ritonavir boosted protease inhibitor treatment among darunavir+ritonavir or lopinavir+ritonavir;
  • Patients' HIV plasma viral load ≤150,000 copies mL-1 at any monitoring time (apart measurement during primo-infection if recorded);
  • Patients with HIV plasma viral load persistently ≤ 50 copies mL-1 during the 12 months prior to screening;
  • Patients' CD4+ T cells count ≥ 300 cells per mm3 at any time since diagnosis;
  • Patient's CD4+ T cells count < 500 cells per mm3 at least once from diagnosis to initiation of antiretroviral treatment;
  • Patients with CD4+ T cells count ≥ 600 cells per mm3 at baseline;
  • Man or woman aged 18-55 years;

Exclusion Criteria

  • HIV-2 infection;
  • Patient treated by HIV entry of fusion inhibitors;
  • Patient treated by HIV integrase inhibitors;
  • Patient displaying any HIV protease inhibitor resistance mutation as listed in the current version of the HIV drug resistance database (Stanford University);
  • Patient having undergone virological failure as defined by a viral load ≥ 500 copies mL-1 confirmed by a second measure, since initiation of treatment;
  • More than 2 blips with viral load comprised between 50 and 500 copies mL-1 during the 12 months prior inclusion;
  • History of an AIDS-defining clinical illness;
  • Concomitant AIDS-related opportunistic disease;
  • History of allergic disease, anaphylaxis or reactions likely to be triggered or exacerbated by any component of the vaccine such as lactose;
  • Acute or chronic infectious disease other than AIDS (include but not limited to viral hepatitis such as hepatitis B and hepatitis C, active tuberculosis, active syphilis, HTLV-1, HTLV-2);
  • Acute, chronic or history of clinically relevant pulmonary, cardiovascular, gastrointestinal, hepatic, pancreatic or renal functional abnormality, encephalopathy, neuropathy or unstable CNS pathology, angina or cardiac arrhythmias, or any other clinically significant medical problems as determined by physical examination and/or laboratory screening tests and/or medical history;
  • Severe hepatic impairment;
  • Serious dyslipidaemia;
  • Severe disorders of blood coagulation;
  • Known or suspected allergy to egg phospholipids, soy proteins and/or peanut;
  • Acute, chronic or history of immunodeficiency or autoimmune disease other than HIV infection;
  • Unstable asthma (defined as sudden acute attacks occurring in less than three hours without an obvious trigger, hospitalisation for asthma in the last two years); food or wine induced asthma;
  • History of malignancy unless there has been surgical excision that is considered to have achieved cure;
  • Active malignancy that may require chemotherapy or radiation therapy;
  • Seizure disorder or any history of prior seizure;
  • Subjects planning to receive a prophylactic or therapeutic vaccination during the study except Influenza immunization;
  • Subjects who have received any vaccination for the 3 months prior the first injection;
  • Subjects having an infective exacerbation as defined as a requirement of inhaled, oral, or intravenous antibiotics at W-2 or later;
  • Serious illness requiring systemic treatment and/or hospitalization within 7 days prior to baseline;
  • Pregnant or breast-feeding woman;
  • Any contraindication of intramuscular injection;
  • Active drug or alcohol abuse or dependence;
  • Any condition, which in the opinion of the investigator, could compromise the subject's safety or adherence to the study protocol.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02054286


Locations
Belgium
CHU Saint-Pierre
Bruxelles, Belgium, B-1000
CHU Liège
Liège, Belgium, B-4000
France
CHU Clermont-Ferrand
Clermont-Ferrand, France, 65003
CHU Dijon
Dijon, France, 21079
CHU Croix-Rousse
Lyon, France, 69317
Hôpital Saint-Louis
Paris, France, 75010
CIC Cochin-Pasteur; Hôpital Cochin
Paris, France, 75014
CHU Rennes
Rennes, France, 35033
Hôpital Nord
Saint-Etienne, France, 42055
CHU Strasbourg
Strasbourg, France, 6091
Hôpital Purpan
Toulouse, France, 31059
Sponsors and Collaborators
Theravectys S.A.
Investigators
Principal Investigator: Odile Launay, Pr CIC Cochin-Pasteur; Hôpital Cochin; Paris

Responsible Party: Theravectys S.A.
ClinicalTrials.gov Identifier: NCT02054286     History of Changes
Other Study ID Numbers: THV01-11-01
First Posted: February 4, 2014    Key Record Dates
Last Update Posted: October 18, 2018
Last Verified: October 2018

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases