A Trial in Subjects Suspected to Have Tuberculosis, Comparing the Diagnostic Performance of C-Tb to QuantiFERON®, in Combination With a Safety Assessment of C-Tb Versus Tuberculin PPD RT23 SSI

NCT01642888 | Completed Phase 3 DMC

• 2 other identifiers: TESEC-052011-005078-40
• Study Type: interventional
• Target: 1,190
• Locations: 1 country
• Sites: 9

Brief Summary

Tuberculosis (TB) continues to be one of the most serious bacterial infections worldwide and therefore new improved diagnostic tests are needed to help doctors in diagnosing TB. The new skin test is named C-Tb. Like the current tuberculin skin test, PPD, the C-Tb test is injected just under the skin and will, when positive, show redness and/or swelling at the injection site while a negative test will leave no reactions. The investigators hope that this new C-Tb skin test will be more precise (specific) than the PPD test, as the PPD test e.g. may show a reaction if the person tested is BCG vaccinated. The aim of this trial is to test the C-Tb skin test in volunteers suspected of having TB disease. With focus on age, HIV status and CD4 count the following analyses are done (in an overall perspective):

• To compare the C-Tb test to a blood test, the QuantiFERON test.
• To compare the C-Tb test to the PPD test that is currently being used.
• To assess the safety of the C-Tb test.

Conditions

Tuberculosis

Outcome Measures

Primary Outcomes (2)

• To evaluate the diagnostic performance of C-Tb in relation to age, HIV and CD4 counts

  Onset between the injections and 28 days after the injections

• To evaluate the clinical safety of C-Tb, with emphasis on children and HIV positive participants

  Onset between the injections and 28 days after the injections

Secondary Outcomes (9)

• To evaluate the difference in sensitivity between C-Tb and QuantiFERON®-TB Gold in-Tube in trial participants with confirmed TB diagnosis, overall, and according to age and HIV status.

  From injections to 2-3 days after the injections

• To evaluate the difference in sensitivity between C-Tb and Tuberculin PPD RT23 SSI in trial participants with confirmed TB diagnosis overall, and according to age and HIV status.

  Onset between the injections and 28 days after the injections

• To evaluate the difference in specificity between C-Tb and QuantiFERON®-TB Gold in-Tube in the control group of 100 children aged 5 - 11 years with no TB symptoms and no known exposure to MTb overall, and according to age.

  From injections to 2-3 days after the injections

• To evaluate the difference in specificity between C-Tb and Tuberculin PPD RT23 SSI in the control group of 100 children aged 5 - 11 years with no TB symptoms and no known exposure to MTb overall, and according to age.

  Onset between the injections and 28 days after the injections

• To compare the diagnostic outcome of C-Tb to that of QuantiFERON®-TB Gold in-Tube using a latent class approach

  From injections to 2-3 days after the injections

Study Arms (2)

0.1 µg/0.1 mL C-Tb

EXPERIMENTAL

The C-Tb and 2 T.U. Tuberculin PPD RT 23 SSI agents are given concomitantly to each volunteer in the RIGHT and LEFT forearms according to a double blind randomisation scheme

Biological: C-Tb

2 T.U. Tuberculin PPD RT 23 SSI

ACTIVE COMPARATOR

The C-Tb and 2 T.U. Tuberculin PPD RT 23 SSI agents are given concomitantly to each volunteer in the RIGHT and LEFT forearms according to a double blind randomisation scheme

Biological: 2 T.U. Tuberculin PPD RT 23 SSI

Interventions

C-Tb BIOLOGICAL

The C-Tb agent is administered by the Mantoux injection technique to each volunteer in the RIGHT or LEFT forearm according to a double blind randomisation scheme

0.1 µg/0.1 mL C-Tb

2 T.U. Tuberculin PPD RT 23 SSI BIOLOGICAL

The 2 T.U. Tuberculin PPD RT 23 SSI agent is administered by the Mantoux injection technique to each volunteer in the RIGHT or LEFT forearm according to a double blind randomisation scheme

2 T.U. Tuberculin PPD RT 23 SSI

Eligibility Criteria

• Age: 28 Days - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV NEGATIVE PARTICIPANTS:
• Participants between 5 and 65 years attending the TB clinic due to suspicion of TB disease
• Infants, toddlers and children between 28 days and 4 years must either have symptoms or signs of TB or be in close contact to a smear positive pulmonary TB case (more than 6 hours/day for at least five days)
• Is between 28 days and 65 years of age
• Participant, parent or legal guardian has signed the informed consent
• Is HIV negative confirmed by two rapid tests. However, children between 28 days and 4 years may have an unknown HIV status and may receive antiretroviral therapy (ART) or have breastfeeding mothers on ART
• Is willing and likely to comply with the trial procedures
• Is prepared to grant authorized persons access to their medical record
• HIV POSITIVE PARTICIPANTS:
• Participants between 5 and 65 years attending the TB clinic due to suspicion of TB disease
• Infants, toddlers and children between 28 days and 4 years must either have symptoms\* or signs\*\* of TB or be in close contact to a smear positive pulmonary TB case (more than 6 hours/day for at least five days)
• Is between 28 days and 65 years of age
• Participant, parent or legal guardian has signed the informed consent
• Is HIV positive confirmed by:
• two positive rapid tests or

You may not qualify if:

• HIV NEGATIVE PARTICIPANTS:
• Has a confirmed diagnosis of tuberculosis at Screening Visit
• Is pregnant, breastfeeding or intending to get pregnant during the trial period
• Is a female of child bearing potential (12 years of age or older) 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 (e.g., Hodgkin's disease, lymphoma, leukaemia, sarcoidosis)
• Has a current skin condition which interferes with the reading of the C-Tb and PPD 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 participant, 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 trial
• HIV POSITIVE PARTICIPANTS:
• Has a confirmed diagnosis of tuberculosis at Screening Visit
• Is pregnant, breastfeeding or intending to get pregnant during the trial period
• Is a female of child bearing potential (12 years of age or older) 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)

Sponsors & Collaborators

• Statens Serum Institut: lead

Study Sites (9)

Primecure Medicentre, Mercantile Hospital

Port Elizabeth, Eastern Cape, 6014, South Africa

Location

Worthwhile Clinical Trials, Lakeview Hospital

Benoni, Gauteng, 1501, South Africa

Location

Synnyside Medi-Clinic

Pretoria, Gauteng, 0002, South Africa

Location

Synexus Stanza Bopape Clinic

Pretoria, Gauteng, 0122, South Africa

Location

Setshaba Research Centre

Pretoria, Gauteng, 0152, South Africa

Location

M2 Karl Bremer Hospital

Bellville, Cape Town, Western Cape, 7530, South Africa

Location

Tiervlei Trial Centre, Karl Bremer Hospital

Bellville, Cape Town, Western Cape, 7530, South Africa

Location

UCT Lung Institute, Groote Schuur Hospital

Cape Town, Western Cape, 7925, South Africa

Location

Be Part Yoluntu Centre

Paarl, Western Cape, 7626, South Africa

Location

Related Publications (1)

• Aggerbeck H, Ruhwald M, Hoff ST, Borregaard B, Hellstrom E, Malahleha M, Siebert M, Gani M, Seopela V, Diacon A, Lourens M, Andersen P, Dheda K. C-Tb skin test to diagnose Mycobacterium tuberculosis infection in children and HIV-infected adults: A phase 3 trial. PLoS One. 2018 Sep 24;13(9):e0204554. doi: 10.1371/journal.pone.0204554. eCollection 2018.

  PMID: 30248152 DERIVED

MeSH Terms

Conditions

Tuberculosis

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Andreas Diacon, MD

  M2 Karl Bremer Hospital

  PRINCIPAL INVESTIGATOR

• Henrik Aggerbeck, M.Sc.

  Statens Serum Institut

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 5, 2012
• First Posted: July 17, 2012
• Study Start: September 1, 2012
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: April 14, 2016

Record last verified: 2016-04

Locations

ZA (9)