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).

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Theravectys S.A.
ClinicalTrials.gov Identifier:
NCT02054286
First received: February 1, 2014
Last updated: February 3, 2014
Last verified: February 2014
  Purpose

The objective of this Phase I/II trial is to evaluate the safety, tolerability and immunogenicity of THV01 compared to a 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 a placebo group.

36 patients will be enrolled. 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 efficient first steps of the mode of action of THV01. 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.

End of study will occur once the 36th patient has reached his visit at Week 36 (i.e. 36 weeks after having received the first administration).


Condition Intervention Phase
HIV Infection
Biological: THV01-1
Biological: THV01-2
Biological: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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)

Resource links provided by NLM:


Further study details as provided by Theravectys S.A.:

Primary Outcome Measures:
  • Safety and tolerability [ Time Frame: Week 0 - Week 24 ] [ Designated as safety issue: Yes ]
    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:
  • Safety and tolerability [ Time Frame: Baseline - Week 0 & Week 24 - Week 36 ] [ Designated as safety issue: Yes ]
    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.

  • Immunogenicity [ Time Frame: Baseline - Week 36 (several timepoints) ] [ Designated as safety issue: No ]
    Monitoring the cellular immune response in the treatment group versus placebo.


Estimated Enrollment: 36
Study Start Date: December 2012
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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 will 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.

End of study is once the last patient has reached his Week 36 visit.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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
CIC Cochin-Pasteur; Hôpital Cochin
Paris, France, 75014
Hôpital Saint-Louis
Paris, France, 75010
CHU Rennes
Rennes, France, 35033
Hôpital Nord
Saint-Etienne, France, 42055
CHU Strasbourg
Strasbourg, France, 6091
Hôpital Purpan
Toulouse, France, 31059
CHU Nancy-Brabois
Vandoeuvre-les-Nancy, France, 54511
Sponsors and Collaborators
Theravectys S.A.
Investigators
Principal Investigator: Odile Launay, Pr CIC Cochin-Pasteur; Hôpital Cochin; Paris
  More Information

No publications provided

Responsible Party: Theravectys S.A.
ClinicalTrials.gov Identifier: NCT02054286     History of Changes
Other Study ID Numbers: THV01-11-01
Study First Received: February 1, 2014
Last Updated: February 3, 2014
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
Belgium: Federal Agency for Medicines and Health Products, FAMHP

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

ClinicalTrials.gov processed this record on September 16, 2014