Clinical trial NCT01779102: Safety Study Investigating if Concomitant Injections of C-Tb and 2 T.U Tuberculin Affect Induration Responses
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Tuberculosis
Lead sponsor: Statens Serum Institut
Sponsor class: OTHER
First posted: 2013-01-30
Enrollment: 456
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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)
timeFrame: Onset from the injection(s) to 28 days after the injections
measure: 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
timeFrame: Onset from the injection(s) to 28 days after the injections
Secondary outcomes:
measure: 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
timeFrame: Onset from the injection(s) to 28 days after the injections
measure: To compare the C-Tb test's ability to identify positive results in Tuberculosis infected patients with the PPD RT 23 test
timeFrame: Onset from the injection(s) to 28 days after the injections
measure: 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
timeFrame: Onset from the injection(s) to 28 days after the injections
Other outcomes:
Locations:
city: Paarl
country: South Africa
facility: Be Part Yoluntu Centre
state: Western Cape
city: Cape Town
country: South Africa
facility: TASK, M2, Karl Bremer Hospital,
city: Cape Town
country: South Africa
facility: Tiervlei Trial Centre, Karl Bremer Hospital
city: Cape Town
country: South Africa
facility: UCT Lung Institute
city: Port Elizabeth
country: South Africa
facility: Primecure Medicentre
city: Pretoria
country: South Africa
facility: Synexus Stanza Bopape Clinic
city: Pretoria
country: South Africa
facility: Setshaba Research Centre
Study officials:
affiliation: Statens Serum Institut
name: Pernille N Tingskov, BN, RN
role: STUDY_DIRECTOR
affiliation: UCT Lung Institute, University of Cape Town
name: Keertan Dheda, MD, Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.