Clinical Trial to Investigate Therapeutic Vaccine (RUTI) Against Tuberculosis (TB)

Double-Blind, Randomized, Placebo-Controlled, Phase IIb Clinical Trial to Investigate the Efficacy of RUTI® Therapeutic Vaccination as Adjuvant of Tuberculosis Chemotherapy

Prospective, randomized, double-blind, multicentre, placebo-controlled clinical phase IIb trial to evaluate efficacy of RUTI® vaccine in DS- (Drug-Sensitive) and MDR-TB (Multidrug-resistant) patients favourably responding to standard MDR-TB treatment. Time point of vaccination starts upon completion of 1 week of standard DS-TB treatment (cohort A), and another cohort of patients will be vaccinated upon completion of 1 month of standard MDR-TB treatment (cohort B). All the patients will be followed up to the end of the treatment.

Study Overview

• Status: Completed
• Conditions: Tuberculosis, Pulmonary
• Intervention / Treatment: Biological: RUTI®; Biological: Placebo

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Phase 2

Contacts and Locations

Study Locations

• India
  • New Delhi, India, 11002
    • All India Institute Of Medical Sciences (AIIMS)
  • Tripura, India, 799006
    • Agartala Government Medical College (AGMC)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Diagnosed with pulmonary DS- or MDR-TB, and managed with standard-care TB drugs accordingly;
2. Attending a TB unit / hospital routinely diagnosed with pulmonary DS- or MDR-TB with clinical status ≥ 6 with Bandim TB score combined with chest radiography; and microbiological criteria (MGIT sputum culture), by using rapid genetic testing, gene Xpert;
3. Patients who have not received any anti-tubercular treatment in last 6 months

4. Females and males aged ≥ 18;

   • females of non-childbearing potential: at least 2 years post- menopausal or surgically sterile (e.g. tubal ligation);
   • females of childbearing potential (including females less than 2 years postmenopausal) must have a negative pregnancy test at enrolment and must agree to use highly effective methods of birth control (i.e. diaphragm plus spermicide or male condom plus spermicide, oral contraceptive in combination with a second method, contraceptive implant, injectable contraceptive, indwelling intrauterine device, sexual abstinence, or a vasectomized partner) while participating in the study;
   • males must agree to use a double barrier method of contraception (condom plus spermicide or diaphragm plus spermicide) while participating in the study; or the male patient or his female partner must be surgically sterile (e.g. vasectomy, tubal ligation) or the female partner must be post-menopausal;
5. The patient must provide written informed consent;
6. The patient must be willing and able to attend all study visits and comply with all study procedures.

Inclusion criteria for vaccination

1. Having successfully completed 1 week or 1 month (depending on the cohort) of DS or MDR-TB treatment, respectively, fully supervised; and with beneficial initial response to therapy, evidenced by clinical response.

Exclusion Criteria:

1. Inability to provide written informed consent;
2. Women reported, or detected, or willing to be pregnant during the trial period;
3. Severity of illness precluding full evaluation: expected early death, evidenced by respiratory failure, low blood pressure, WHO performance score 3-4
4. Patients with extra-pulmonary tuberculosis
5. Major co-morbid conditions precluding full evaluation, i.e., HIV positive, chronic renal failure, chronic liver failure, Malignancy, patients taking any immunosuppressant drug, active lung cancer, acute coronary syndrome, heart failure exceeding NYHA class 2;
6. Presence of secondary immunodeficiency states: Organ transplantation, diabetes mellitus

7. Any of the following laboratory parameters:

   • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 x upper limit of normal (ULN)
   • Total bilirubin > 2 x ULN
   • Neutrophil count ≤ 500 neutrophils / mm3
   • Platelet count < 50,000 cells / mm3
8. Cytotoxic chemotherapy or radiation therapy within the previous 3 months;
9. Blood transfusion in the last three weeks prior to the trial; 10.Patients with history of alcohol or drug abuse

11. Documented allergy to TB vaccines, notably, to the RUTI® vaccine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RUTI® arm; A dose of 25 μg of of RUTI vaccine will be given at week 1 (Cohort A-DS TB Patients) or month 1 (Cohort B-MDR TB Patients) after starting standard TB treatment.	Biological: RUTI®; Participants randomised to this arm will receive one single dose of RUTI® vaccine in the right/left deltoid muscle.
Placebo Comparator: Placebo arm; Placebo will be given at week 1 (Cohort A-DS TB Patients) or month 1 (Cohort B-MDR TB Patients) after starting standard TB treatment.	Biological: Placebo; Participants randomised to this arm will receive aone single dose of matching RUTI® placebo in the right / left deltoid muscle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with Sputum Culture Negative	Difference between intervention and control group	Up to Week 2 for Cohort A and Month 1.5 for Cohort B

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with Sputum Culture Negative	Difference between intervention and control group	Up to Week 8 for Cohort A and Month 6 for Cohort B
Proportion of patients with reduction of bacillary load	Difference between intervention and control group based upon Time to detection (TTD) signal in MGIT	Up to Week 2 and 8 (Cohort A); and Months 1.5 and 6 (Cohort B)
Proportion of patients with improvement of clinical signs and symptoms	Difference between intervention and control group based upon Bandin	Up to Week 2 and 8 (Cohort A); and Months 1.5 and 6 (Cohort B)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical safety parameters related to vaccination	Serious adverse events (SAEs) by CTCAE v4.0	Through study completion, an average of 2 year
Local tolerability	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 in terms of site of injection for redness, pain, swelling, induration and functional limitation	Up to Week 8

Collaborators and Investigators

• Sponsor: Archivel Farma S.L.
• Investigators: Principal Investigator: Randeep Guleria, Prof, All India Institute of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2021
• Primary Completion (Actual): June 19, 2025
• Study Completion (Actual): June 19, 2025

Study Registration Dates

• First Submitted: May 31, 2021
• First Submitted That Met QC Criteria: June 8, 2021
• First Posted (Actual): June 9, 2021

Study Record Updates

• Last Update Posted (Actual): December 10, 2025
• Last Update Submitted That Met QC Criteria: December 3, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Lung Diseases; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Tuberculosis, Pulmonary
• Other Study ID Numbers: RUTIP2-2019-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No