NAcGM3/VSSP-aids-patients drug resistant to antiretroviral treatment-Phase I-II

• Register: RPCEC
• Last refreshed on: 29 April 2024
• Main ID: RPCEC00000213
• Date of registration: 22/04/2016
• Prospective Registration: No
• Primary sponsor: Center of Molecular Immunology (CIM)
• Public title: NAcGM3/VSSP-aids-patients drug resistant to antiretroviral treatment-Phase I-II
• Scientific title: Evaluation of safety and effect of four doses level of NAcGM3/VSSP formulation as immunopotentiator by subcutaneous route in the treatment of aids patients drug resistant to antiretroviral treatment. - Not applicable
• Date of first enrolment: 28/01/2015
• Target sample size: 25
• Recruitment status: Complete
• URL: https://rpcec.sld.cu/en/trials/RPCEC00000213-En
• Study type: Interventional
• Study design: Allocation: Randomized controlled trial. Masking: Double Blind. Control group: Placebo. Assignment: Parallel. Purpose: Treatment
• Phase: 1-2

Countries of recruitment

Cuba

Contacts

• Name: Adriana Carr Perez
• Affiliation: Center of Molecular Immunology (CIM)

• Name: Vianka Calas Hechevarria
• Affiliation: Tropical Medicine Institute Pedro Kouri (IPK)

Key inclusion & exclusion criteria

Inclusion criteria: 1. Patients who have signed informed consent.
2. AIDS patients with antiretroviral treatment and evidence of multidrug resistance or with CD4 counts below 200 cells / uL for more than 2 consecutive assessments in the last 6 months with controlled viral load (not detectable or with values below the range 1 000 copies).
3. Patients aged between 18 and 50 years (including both).
4. Patients with overall according to WHO between 0 and 1.
5. Patients who have functioning of organs and bone marrow as defined by the following parameters (a) Hematopoietic:
Hb>=100 g / L, Leukocytes>= 3 x 109 cells / L, granulocytes>= 1 x 109 cells / L, Platelets >= 150 x 109 cells / L; b) Liver (No more than five times the upper limit of normal (ULN) *), Bilirubin: 17 pmol / L (LSN *), ALAT: 40 U / L (LSN *)
ASAT: 40 U / L (LSN *), Alkaline Phosphatase: 279 U / L *, LDH within normal levels: 214 U / L (LSN); c) Renal: Serum creatinine<= 132 pmol / L)
6. Life expectancy of 6 months or more.

Exclusion criteria: 1. Patients who have previously received the investigational product .
2. Patients receiving other investigational product .
3. Patients with known hypersensitivity to any component of the formulation.
4. pregnant or lactating patients
5. Patients of childbearing age who are not using an appropriate method of contraception ( intrauterine devices, hormonal contraceptives , barrier methods or tubal ligation) . If male (vasectomy , condom use ) during treatment .
6. Patients with acute allergic conditions or history of severe allergic reactions.
7. Patients suffering from uncontrolled intercurrent illness including, but not limited to : active infections , symptomatic congestive heart failure, unstable angina , cardiac arrhythmia and psychiatric diseases involving the incompetence of the subject.
8. Patients with other malignant disease treated correctly in the previous 5 years , except in situ cancer.
9. Virus infection Hepatitis B or C.
10. Opportunistic at the time of inclusion in the study infection


Age minimum: 18 years
Age maximum: 50 years
Gender: Male/Female

Health Condition(s) or Problem(s) studied

RNA Virus Infections

Acquired Immunodeficiency Syndrome

Acquired immunodeficiency syndrome (AIDS)

Immune System Diseases

Immunologic Deficiency Syndromes

Slow Virus Diseases

Sexually Transmitted Diseases, Viral

Retroviridae Infections

HIV Infections

Lentivirus Infections

Sexually Transmitted Diseases

Intervention(s)

Placebos

Adjuvants, Immunologic

Vaccines

Injections, Subcutaneous

N-Acetylneuraminic Acid

Proteolipids

Gangliosides

NAcGM3/VSSP

G(M3) Ganglioside

Interventions in Phase I
Four Doses Level
Group I (experimental): NAcGM3/VSSP vaccine (dose 150 µg) will be administered by subcutaneous route. The first 5 doses will be administered each 14 days (± 7 days of tolerance), the next 10 doses will be administered each 28 days (± 15 days of tolerance), to complete a year of treatment.

Group II (experimental): NAcGM3/VSSP vaccine (dose 300 µg) will be administered by subcutaneous route. The first 5 doses will be administered each 14 days (± 7 days of tolerance), the next 10 doses will be administered each 28 days (± 15 days of tolerance), to complete a year of treatment.

Group III (experimental): NAcGM3/VSSP vaccine (doses 600 µg) will be administered by subcutaneous route. The first 5 doses will be administered each 14 days (± 7 days of tolerance), the next 10 doses will be administered each 28 days (± 15 days of tolerance), to complete a year of treatment.

Group IV (experimental): NAcGM3/VSSP vaccine (doses 900 µg) will be administered by subcutaneous route. The first 5 doses will be administered each 14 days (± 7 days of tolerance), the next 10 doses will be administered each 28 days (± 15 days of tolerance), to complete a year of treatment.

Patients who presented favorable response to the treatment, after 15 administration, will can continuous with the same administration of formulation every 28 days (± 15 days of tolerance, always remain with the performance status during the follow of protocol another year and after that under clinical consideration.

Interventions in Phase II
Group I ( study) : Depending on the selected dose Phase I is administered subcutaneously , the first 5 doses at intervals of 14 days ( ± 7 days tolerance), the following 10 doses at intervals of 28 d

Primary Outcome(s)

Phase I
Optimal therapeutic dose (Level of dose in that they yield minor patients' number with new opportunistic diseases or deaths to the 12 months, once a minor toxicity was associated (adverse serious event, related to the formulation). Measuring time: 168, 336 days.
Phase II
Clinical response (Appearance of opportunistic bigger diseases or death in the period of treatment. The opportunistic diseases will be evaluated using the criteria of the Control Disease Center for AIDS patients of the United States). Measuring time: 168, 336 days.
Adverse serious events related to with the formulation (The adverse events will be evaluated using the World Health Organization toxicity criteria). Measuring time: 168, 336 days.

Secondary Outcome(s)

Immunopotenciator Effect (It will evaluate based on the decrease or no increase in CD4 levels in the course of treatment). Measuring time: 168, 336 days.
Virologic response (It will evaluate based on no increase in viral load in at least one decimal log or decrease it, in the course of treatment). Measuring time: 168, 336 days.
Immunologic response (Values of CD3, CD4, CD8, NK, CD4CD25FoxP3. The result will be collected by those units in the institution). Measuring time: 168, 336 days.
Quality of life (It will evaluate through the Spanish version of the MOS-HIV (for its acronym in English Medical Outcomes Study -Human Immunodeficiency Virus), validated in the Cuban population by IPK. It is a questionnaire of Quality of life for aids Cuban patients). Measuring time: 0, 168, 336 days.
Safety.
Toxicity (Occurrence of any EA, description, duration, intensity, severity, outcome, attitude towards treatment and causation). This outcome will measure every 28 days.
- Occurrence of any AE (Yes, No)
- Description AE (name of the event)
- Duration of AE (Difference between the start and end dates of the adverse event)
- AE Intensity (It is classified according to the nomenclature and intensity criteria to assess the severity of adverse events in AIDS patients adult and pediatric version 1.0, December 2004; with clarification of August 2009. It includes the following categories: mild, moderate, severe, EA potentially life-threatening or EA that produces death.
- Causality relationship (1. Final, 2. Very Likely, 3. Probable, 4.Possible. 5. Not related, 6.Unknown)
- Seriousness / Gravity (Serious, Not serious. Are severe/serious adverse events those that 1. Produce death,
2. Threaten life, 3. Require / prolonged hospitalization, 4. Produce disability / persistent or significant disability or
5. Produce birth defect or congenital anomaly)
Results of laboratory tests. Measuring time: every 28 days.
Hematopoietic Laboratory (Hb (g/L), Leukocyte (109 cells/L), Granulocyte (109 cells/L), Platelets (109 cells/L). Measuring time: every 28 days.
Liver Laboratotry (Bilirubin (µmol/L), ALAT (U/L), ASAT (U/L), Alkaline Phosphatase (U/L), LDH (U/L)). Measuring time: every 28 days.
Renal Laboratory (Serum Creatinine (µmol/L)). Measuring time: every 28 days.

Secondary ID(s)

IICRD-EC-155

Source(s) of Monetary Support

Center of Molecular Immunology (CIM)Tropical Medicine Institute Pedro Kouri (PK)

Secondary Sponsor(s)

Not applicable