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).

NCT02054286 | Completed Phase 1 DMC

• 1 other identifier: THV01-11-01
• Study Type: interventional
• Target: 38
• Locations: 2 countries
• Sites: 11

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.

Conditions

HIV Infection

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability

  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.

  From Week 0 to Week 24

Secondary Outcomes (2)

• Safety and tolerability

  From baseline to Week 88 (or early termination).

• Immunogenicity

  From baseline to Week 88 (or early termination).

Other Outcomes (2)

• HIV reservoir (HIV total DNA)

  From baseline to five years after the prime injection.

• Long term safety

  From Week 88 to five years after the prime injection.

Study Arms (3)

Group 1: THV01 (5.10E+6 TU) or Placebo

EXPERIMENTAL

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; Biological: THV01-2; Biological: Placebo

Group 2: THV01 (5.10E+7 TU) or Placebo

EXPERIMENTAL

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; Biological: THV01-2; Biological: Placebo

Group 3: THV01 (5.10E+8 TU) or Placebo

EXPERIMENTAL

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; Biological: THV01-2; Biological: Placebo

Interventions

THV01-1 BIOLOGICAL

Intramuscular injection of THV01-1 (week 0)

Also known as: lentiviral vector ancoding an HIV antigen

Group 1: THV01 (5.10E+6 TU) or Placebo; Group 2: THV01 (5.10E+7 TU) or Placebo; Group 3: THV01 (5.10E+8 TU) or Placebo

THV01-2 BIOLOGICAL

Intramuscular injection of THV01-2 (week 8)

Also known as: lentiviral vector encoding an HIV antigen

Group 1: THV01 (5.10E+6 TU) or Placebo; Group 2: THV01 (5.10E+7 TU) or Placebo; Group 3: THV01 (5.10E+8 TU) or Placebo

Placebo BIOLOGICAL

Intramuscular injection of placebo matching THV01-1 and THV01-2

Also known as: Placebo matching THV01-1 and THV01-2

Group 1: THV01 (5.10E+6 TU) or Placebo; Group 2: THV01 (5.10E+7 TU) or Placebo; Group 3: THV01 (5.10E+8 TU) or Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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;

You may not qualify if:

• 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;
• 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;

Sponsors & Collaborators

• Theravectys S.A.: lead

Study Sites (11)

CHU Saint-Pierre

Brussels, B-1000, Belgium

Location

CHU Liège

Liège, B-4000, Belgium

Location

CHU Clermont-Ferrand

Clermont-Ferrand, 65003, France

Location

CHU Dijon

Dijon, 21079, France

Location

CHU Croix-Rousse

Lyon, 69317, France

Location

Hôpital Saint-Louis

Paris, 75010, France

Location

CIC Cochin-Pasteur; Hôpital Cochin

Paris, 75014, France

Location

CHU Rennes

Rennes, 35033, France

Location

Hôpital Nord

Saint-Etienne, 42055, France

Location

CHU Strasbourg

Strasbourg, 6091, France

Location

Hôpital Purpan

Toulouse, 31059, France

Location

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Odile Launay, Pr

  CIC Cochin-Pasteur; Hôpital Cochin; Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2014
• First Posted: February 4, 2014
• Study Start: December 1, 2012
• Primary Completion: August 1, 2014
• Study Completion: February 27, 2019
• Last Updated: April 11, 2019

Record last verified: 2019-04

Locations

BE (2); FR (9)