Safety Study Investigating if Concomitant Injections of C-Tb and 2 T.U Tuberculin Affect Induration Responses (TESEC-07)

A Phase II/III Trial Investigating if Concomitant Injections of the Diagnostic Agents C-Tb and 2 T.U Tuberculin PPD RT 23 SSI Affect the Induration Responses in Combination With a Safety Assessment of C-Tb

A new, more specific skin test to detect tuberculosis has been developed by Statens Serum Institut in Denmark. The new skin test is named C-Tb and like the current Tuberculin a positive test result will show as redness and/or induration at the injection site, while a negative test will leave no reactions.

The aim of this study is to address if the size of induration and the sensitivity of C-Tb is influenced by concomitant injections of C-Tb and Tuberculin. Furthermore, the intention is to evaluate the safety of C-Tb when injected alone or concomitantly with Tuberculin.

Study Overview

• Status: Completed
• Conditions: Tuberculosis
• Intervention / Treatment: Biological: C-Tb; Biological: Tuberculin PPD RT 23 SSI; Biological: C-Tb / Tuberculin PPD RT 23 SSI

Detailed Description

The TESEC-07 trial is a GCP double blind randomised controlled phase II/III trial investigating if concomitant injections of the diagnostic agents C-Tb and 2 T.U Tuberculin PPD RT 23 SSI affect the induration responses in combination with a safety assessment of C-Tb. TESEC-07 is a multi-centre trial and will be conducted in South Africa in patients recently diagnosed with TB comprising 360 HIV negative and 90 HIV positive adults allocated to 3 trial groups.

• A within group paired comparison of 0.1 μg/0.1 mL C-Tb and PPD RT 23 in 150 TB patients. The C-Tb and PPD RT 23 agents are given concomitantly to each volunteer in the RIGHT AND LEFT forearms according to a randomisation scheme.
• A group of 150 TB patients will only receive the C-Tb agent randomised to either RIGHT or LEFT forearm.
• A group of 150 TB patients will only receive the reference agent PPD RT 23 randomised to either RIGHT or LEFT forearm.

• Study Type: Interventional
• Enrollment (Actual): 456
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• South Africa
  • Cape Town, South Africa, 7530
    • TASK, M2, Karl Bremer Hospital,
  • Cape Town, South Africa, 7530
    • Tiervlei Trial Centre, Karl Bremer Hospital
  • Cape Town, South Africa, 7925
    • UCT Lung Institute
  • Port Elizabeth, South Africa, 6014
    • Primecure Medicentre
  • Pretoria, South Africa, 0122
    • Synexus Stanza Bopape Clinic
  • Pretoria, South Africa, 0152
    • Setshaba Research Centre
  • Western Cape
    • Paarl, Western Cape, South Africa, 7626
      • Be Part Yoluntu Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria (HIV Negative patients):

• Has signed an informed consent
• Aged 18 to 65 years

• Has been diagnosed with active pulmonary TB:

  1. has a compatible clinical picture of TB according to South African guidelines with the intention to treat and 1 documented positive culture result or
  2. has a compatible clinical picture of TB according to South African Guidelines with the intention to treat and 1 documented positive GeneXpert analysis
• Is HIV negative confirmed by 2 two rapid tests
• Is willing and likely to comply with the trial procedures
• Is prepared to grant authorized persons access to their medical record

Inclusion Criteria (HIV Positive patients):

• Has signed an informed consent
• Aged 18-65 years

• Has been diagnosed with active pulmonary TB:

  1. has a compatible clinical picture of TB according to South African guidelines with the intention to treat and 1 documented positive culture result or
  2. has a compatible clinical picture of TB according to South African Guidelines with the intention to treat and 1 documented positive GeneXpert analysis

• Is HIV positive confirmed by:

  1. 2 positive rapid tests or
  2. 1 positive rapid tests and an additional confirmatory ELISA
• A CD4 count has been performed
• Is willing and likely to comply with the trial procedures
• Is prepared to grant authorized persons access to their medical records

Exclusion Criteria:

• Has been in treatment for TB for more than 2 weeks
• Has a known MDR/XDR-TB
• Has been vaccinated with a live vaccine within 6 weeks prior to the day of inclusion (e.g. MMR, yellow fever, oral typhoid vaccines) except BCG vaccine
• Has been tuberculin (TST) tested < 12 months prior to the day of inclusion
• Is pregnant, breastfeeding or intending to get pregnant
• Is a female of child bearing potential not willing to use effective barrier (including spermicidal gel), hormonal or intrauterine contraceptive measures during the trial period
• Has an active disease affecting the lymphoid organs except for HIV (e.g., Hodgkin's disease, lymphoma, leukaemia, sarcoidosis)
• Has a current skin condition which interferes with the reading of the skin tests e.g. tattoos, severe scarring, burns/sunburns, rash, eczema, psoriasis, or any other skin disease at or near the injection sites
• Has a condition where blood drawings pose more than minimal risk for the patient, such as haemophilia, other coagulation disorders, or significantly impaired venous access
• Currently participating in another clinical trial with an investigational or non investigational drug or device, or has participated in another clinical trial within the 3 months prior to dosing
• Has participated in previous clinical trials investigating the ESAT-6 and/or CFP-10 antigens
• Has a condition which in the opinion of the investigator is not suitable for participation in the study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 0.1 µg C-Tb; The C-Tb agent is given alone to volunteers in the RIGHT or LEFT forearm according to a double blind randomisation scheme	Biological: C-Tb; C-Tb is administered by the Mantoux injection technique to each volunteer in the RIGHT or LEFT forearm according to a double blind randomisation scheme
Active Comparator: 2 T.U Tuberculin PPD RT 23 SSI; The 2 T.U Tuberculin PPD RT 23 SSI agent is given alone to volunteers in the RIGHT or LEFT forearm according to a double blind randomisation scheme	Biological: Tuberculin PPD RT 23 SSI; Tuberculin is administered by the Mantoux injection technique to each volunteer in the RIGHT or LEFT forearm according to a double blind randomisation scheme
Experimental: 0.1 µg C-Tb / 2 T.U Tuberculin PPD; The C-Tb and 2 T.U Tuberculin PPD RT 23 SSI agents are given concomitantly to volunteers in the RIGHT and LEFT forearms according to a double blind randomisation scheme	Biological: C-Tb / Tuberculin PPD RT 23 SSI; The C-Tb and Tuberculin agents are administered by the Mantoux injection technique to each volunteer in the RIGHT and LEFT forearm according to a double blind randomisation scheme

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To compare the size of induration of C-Tb and PPD RT 23 if injected alone or concomitantly in Tuberculosis infected patients (HIV positives and HIV negatives)	Onset from the injection(s) to 28 days after the injections
To assess if concomitant injections of C-Tb and PPD RT 23 influence the tests abilities to identify positive results of Tuberculosis in Tuberculosis infected patients	Onset from the injection(s) to 28 days after the injections

Secondary Outcome Measures

Outcome Measure	Time Frame
To compare the C-Tb test's ability to identify positive results in Tuberculosis infected patients with the in vitro QuantiFERON®TB Gold In Tube assay in blood collected immediately before application of the C-Tb skin test	Onset from the injection(s) to 28 days after the injections
To compare the C-Tb test's ability to identify positive results in Tuberculosis infected patients with the PPD RT 23 test	Onset from the injection(s) to 28 days after the injections
To assess the safety of C-Tb skin test by investigating laboratory safety parameters and assessing all adverse events (local and systemic) occurring within 28 days after administration of the C-Tb and/or PPD RT 23 tests	Onset from the injection(s) to 28 days after the injections

Collaborators and Investigators

• Sponsor: Statens Serum Institut
• Investigators: Study Director: Pernille N Tingskov, BN, RN, Statens Serum Institut; Principal Investigator: Keertan Dheda, MD, Prof, UCT Lung Institute, University of Cape Town

Publications and helpful links

General Publications

• Aggerbeck H, Ruhwald M, Hoff ST, Tingskov PN, Hellstrom E, Malahleha M, Siebert M, Gani M, Diacon A, Novelijc Z, Andersen P, Dheda K. Interaction between C-Tb and PPD given concomitantly in a split-body randomised controlled trial. Int J Tuberc Lung Dis. 2019 Jan 1;23(1):38-44. doi: 10.5588/ijtld.18.0137. Epub 2018 Dec 20.

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: January 18, 2013
• First Submitted That Met QC Criteria: January 29, 2013
• First Posted (Estimate): January 30, 2013

Study Record Updates

• Last Update Posted (Estimate): April 17, 2015
• Last Update Submitted That Met QC Criteria: April 16, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis
• Other Study ID Numbers: TESEC-07