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

• ClinicalTrials.gov Identifier: NCT04919239
• Recruitment Status: Recruiting
• First Posted: June 9, 2021
• Last Update Posted: March 25, 2022
• Sponsor: Archivel Farma S.L.
• Information provided by (Responsible Party): Archivel Farma S.L.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Tuberculosis, Pulmonary	Biological: RUTI®; Biological: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 140 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Double-Blind, Randomized, Placebo-Controlled, Phase IIb Clinical Trial to Investigate the Efficacy of RUTI® Therapeutic Vaccination as Adjuvant of Tuberculosis Chemotherapy
• Actual Study Start Date: September 22, 2021
• Estimated Primary Completion Date: November 2025
• Estimated Study Completion Date: November 2025

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Percentage of patients with Sputum Culture Negative [ Time Frame: Up to Week 2 for Cohort A and Month 1.5 for Cohort B ]
   Difference between intervention and control group

Secondary Outcome Measures :

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

Other Outcome Measures:

1. Clinical safety parameters related to vaccination [ Time Frame: Through study completion, an average of 2 year ]
   Serious adverse events (SAEs) by CTCAE v4.0
2. Local tolerability [ Time Frame: Up to Week 8 ]
   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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Dipendra K Mitra, Prof; 01126588500; salilmitra2@gmail.com

Locations

India

All India Institute of Medical Sciences (AIIMS); Recruiting

New Delhi, India, 11002

Contact: Dipendra K Mitra, Prof. salilmitra2@gmail.com

Agartala Government Medical College (AGMC); Recruiting

Tripura, India, 799006

Contact: Tapan Majumdar, Dr drtapan1960@gmail.com

Sponsors and Collaborators

Archivel Farma S.L.

Investigators

• Principal Investigator: Randeep Guleria, Prof; All India Institute of Medical Sciences, New Delhi

More Information

• Responsible Party: Archivel Farma S.L.
• ClinicalTrials.gov Identifier: NCT04919239
• Other Study ID Numbers: RUTIP2-2019-01
• First Posted: June 9, 2021
• Last Update Posted: March 25, 2022
• Last Verified: March 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Tuberculosis; Tuberculosis, Pulmonary; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases