Safety and Risk of Sensitisation of the rdESAT-6 + rCFP-10 Skin Test Following Repeated Intradermal Administration

An Open Phase I Clinical Trial on the Safety and Risk of Sensitisation by Escalating Doses and Repeated Injections of the rdESAT-6 + rCFP-10 Skin Test Reagent Following Intradermal Administration to Healthy Adults

The primary objective is to assess the safety of three dose levels (0.01, 0.1 and 1.0 µg) of the rdESAT-6 + rCFP-10 skin test reagent when injected into healthy adults. The secondary objective is to assess the risk of sensitisation of 0.01 and 0.1 µg rdESAT-6 + rCFP-10 when injected twice with time intervals of 6 or 12 weeks to healthy adults.

Study Overview

• Status: Completed
• Conditions: Tuberculosis
• Intervention / Treatment: Biological: rdESAT-6 + rCFP-10

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Rigshospitalet, Epidemiklinikken

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Has signed an informed consent
2. Is willing and likely to be able to comply with the trial procedures
3. Is female/male non-black adult ≥ 18 years and ≤ 55 years of age
4. Is healthy according to a medical examination, medical history and laboratory investigations at inclusion
5. Is prepared to grant authorized persons access to their medical records

Exclusion Criteria:

1. Has a history of tuberculosis or has had a known contact to a person with active tuberculosis
2. Has a positive QuantiFERON-TB Gold In Tube test result at inclusion
3. Laboratory parameters outside of normal range judged by principal investigator to be clinically significant and/or abnormal glucose or protein levels in a urine sample at inclusion
4. Has been in treatment with a product which is likely to modify the immune response within 3 months prior to the day of inclusion (e.g., immunoglobulin, systemic corticosteroids, methotrexate, azathioprine, cyclosporine, infliximab or blood products)
5. Has been vaccinated with a live vaccine within 6 months prior to the day of inclusion (e.g., MMR, yellow fever, or oral typhoid vaccines)
6. Has a known congenital or acquired immune deficiency
7. Has a disease affecting the lymphoid organs (e.g., Hodgkin's disease, lymphoma, leukemia, sarcoidosis)
8. Is known to be infected with HIV, HBV or HCV
9. Has a severe ongoing viral or bacterial infection that might affect the cell mediated immune response at inclusion
10. Has a C-reactive protein (CRP) level > 50 mg/L
11. Has severe scarring, burn, rash, eczema, psoriasis, or any other skin disease at or near the injection site(s)
12. Has a condition in which repeated blood drawings pose more than minimal risk for the volunteer, such as haemophilia, other coagulation disorders, or significantly impaired venous access
13. Is actively participating in another clinical trial or has participated in previous clinical trials investigating the rdESAT-6 skin test reagent
14. Is pregnant according to urine pregnancy test at inclusion
15. Is a female not willing to use contraceptives or is breastfeeding
16. 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: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; two injections 0.01 µg rdESAT-6 + rCFP-10 (6 weeks interval)	Biological: rdESAT-6 + rCFP-10; rdESAT-6 + rCFP-10 skin test administered intradermally by the mantoux injection technique
Experimental: B; two injections 0.01 µg rdESAT-6 + rCFP-10 (12 weeks interval)	Biological: rdESAT-6 + rCFP-10; rdESAT-6 + rCFP-10 skin test administered intradermally by the mantoux injection technique
Experimental: C; two injections 0.1 µg rdESAT-6 + rCFP-10 (6 weeks interval)	Biological: rdESAT-6 + rCFP-10; rdESAT-6 + rCFP-10 skin test administered intradermally by the mantoux injection technique
Experimental: D; two injections 0.1 µg rdESAT-6 + rCFP-10 (12 weeks interval)	Biological: rdESAT-6 + rCFP-10; rdESAT-6 + rCFP-10 skin test administered intradermally by the mantoux injection technique
Experimental: E; one injection 1.0 µg rdESAT-6 + rCFP-10	Biological: rdESAT-6 + rCFP-10; rdESAT-6 + rCFP-10 skin test administered intradermally by the mantoux injection technique

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Local and systemic adverse events with onset after the FIRST (0.01, 0.1 and 1.0 µg) or SECOND (0.01 and 0.1 µg) injection	onset between the first injection and 28 days after the second injection

Secondary Outcome Measures

Outcome Measure	Time Frame
The diameter of induration at the second injection site measured transversely to the long axis of the forearm	72 hours after the second injection

Collaborators and Investigators

• Sponsor: Statens Serum Institut
• Investigators: Study Director: Pernille Nyholm Tingskov, Statens Serum Institut

Publications and helpful links

General Publications

• Bergstedt W, Tingskov PN, Thierry-Carstensen B, Hoff ST, Aggerbeck H, Thomsen VO, Andersen P, Andersen AB. First-in-man open clinical trial of a combined rdESAT-6 and rCFP-10 tuberculosis specific skin test reagent. PLoS One. 2010 Jun 25;5(6):e11277. doi: 10.1371/journal.pone.0011277.

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Actual): July 1, 2009
• Study Completion (Actual): July 1, 2009

Study Registration Dates

• First Submitted: November 17, 2008
• First Submitted That Met QC Criteria: November 17, 2008
• First Posted (Estimate): November 19, 2008

Study Record Updates

• Last Update Posted (Estimate): January 21, 2013
• Last Update Submitted That Met QC Criteria: January 18, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: diagnosis; tuberculosis; skin test; ESAT-6; CFP-10; Skin test for the diagnosis of tuberculosis infection
• 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-01; EUDRACT No.: 2008-001489-96