The TELO-SCOPE Study: Attenuating Telomere Attrition With Danazol. Is There Scope to Dramatically Improve Health Outcomes for Adults and Children With Pulmonary Fibrosis

Pulmonary Fibrosis Clinical Trial

Official title:

The TELO-SCOPE Study: Attenuating Telomere Attrition With Danazol. Is There Scope to Dramatically Improve Health Outcomes for Adults and Children With Pulmonary Fibrosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04638517
• Other study ID #: TELO-SCOPE
• Status: Recruiting
• Phase: Phase 2
• Start date: September 7, 2021
• Est. completion date: June 2025

Study information

• Verified date: December 2023
• Source: The University of Queensland
• Contact: Daniel Chambers
• Phone: 07 3139 4000
• Email: daniel.chambers[@]health.qld.gov.au
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

TELO-SCOPE is a national, multi-centre, double-blind, placebo-controlled, randomised (2:1) trial which will test the hypothesis that, compared to placebo, the addition of danazol to standard of care in pulmonary fibrosis associated with short telomeres is safe and will result in reduced telomere attrition.

Description:

TELO-SCOPE is a national, multi-centre, double-blind, placebo-controlled, randomised trial which will be conducted in subjects aged >5 years with a multi-disciplinary diagnosis of pulmonary fibrosis and with age-adjusted telomere length below the 10th centile in adults; and for children (age < 16 years), a confirmed diagnosis of Dyskeratosis Congenita (DC). Consenting participants who meet all other inclusions and no exclusions will be randomised (n=50, 2:1 (danazol:placebo)) to receive danazol (maximum tolerated dose (up to 800mg daily, two-divided doses) or matched placebo, for 12 months in addition to standard of care background therapy. The primary outcome is change in telomere length at 12 months.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: June 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years and older

Eligibility

Inclusion Criteria:

1. Males and females aged >5 years, able to take capsules orally.

2. Fibrosing interstitial pneumonia (Idiopathic PF, idiopathic non-specific interstitial pneumonia, chronic hypersensitivity pneumonitis, pleuroparenchymal fibroelastosis, unclassifiable interstitial lung disease (ILD)) diagnosed according to the current international guidelines.

3. Age-adjusted peripheral blood leukocyte telomere length < 10th centile on Flow-FISH.

4. FVC > 40% predicted.

5. DLCO > 25% predicted.

6. If receiving background pirfenidone / nintedanib, stable dose for 28 days prior to screening.

7. Able to understand and sign a written informed consent form (or legally authorised representative).

8. Agreement to use a medically approved form of non-hormonal contraception (if of child-bearing potential) (noting that oral contraceptives are advised not to be used concurrently with danazol).

Exclusion Criteria:

1. Actively or imminently listed for lung transplantation.

2. Undergone, awaiting, or likely to require bone marrow transplantation within 12 months.

3. Concurrent enrolment in another study.

4. Females with a positive pregnancy test at screening or currently breastfeeding.

5. Pelvic infection.

6. Past jaundice with oral contraceptives.

7. Undiagnosed abnormal genital bleeding.

8. Undiagnosed ovarian/uterine masses

9. Any history of malignancy likely to result in significant disability or likely to require significant medical or surgical intervention within the next 12 months.

10. History of androgen-dependent tumour.

11. Any condition other than PF that, in the opinion of the investigator, is likely to result in the death of the participant within the next 12 months.

12. History of end-stage liver disease or ALT or AST > 3 times the upper limit of normal.

13. History of end-stage kidney disease requiring dialysis.

14. Markedly impaired cardiac function.

15. Known increased risk of or history of thromboembolism (e.g. Factor V Leiden, Protein C or S deficiency).

16. Uncontrolled hypertension.

17. Uncontrolled lipoprotein disorder.

18. Poorly-controlled diabetes mellitus.

19. History of marked or persistent androgenic reaction to previous gonadal steroid therapy.

20. History of epilepsy induced or worsened by previous gonadal steroid therapy.

21. History of raised intracranial pressure.

22. Known intolerance to danazol.

23. Porphyria.

24. Use of any of the following agents within 28 days before screening: danazol or other androgen therapy, warfarin or other anticoagulant, carbamazepine, phenytoin, investigational therapy, cytotoxic therapy, tacrolimus, cyclosporine.

25. Professional singer due to potential for voice change.

26. Competitive athletes.

27. Prostate specific antigen (PSA) above the upper limit of normal (adult males only).

Related Conditions & MeSH terms

• Dyskeratosis Congenita
• Fibrosis
• Pulmonary Fibrosis
• Telomere Disease
• Telomere Shortening

Intervention

Drug:
• Danazol
Danazol up to 800mg daily in two-divided doses.
• Placebo
Matching placebo.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	The Prince Charles Hospital	Brisbane	Queensland
Australia	The Alfred	Melbourne	Victoria
Australia	The Austin	Melbourne	Victoria
Australia	John Hunter Hospital	Newcastle	New South Wales
Australia	Fiona Stanley Hospital	Perth	Western Australia
Australia	Royal Prince Alfred Hospital	Sydney	New South Wales
Australia	Sydney Children's Hospital	Sydney	New South Wales
Australia	The Children's Hospital Westmead	Sydney	New South Wales

Sponsors (1)

Lead Sponsor	Collaborator
The University of Queensland

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in absolute telomere length from baseline (base pairs)	Telomere length will be measured in absolute terms (base pairs) using the telomere shortest length assay (TeSLA).	12 months
Secondary	Number of participants with treatment-emergent adverse events		12 months
Secondary	Number of Participants With Death or Non-Elective Hospitalisation		12 months
Secondary	Change in telomere length from baseline to 3, 6 and 9 months (base pairs)		3, 6 and 9 months
Secondary	Change in forced vital capacity (FVC) at 6 and 12 months	FVC is measured as the volume of air exhaled during spirometry.	6 and 12 months
Secondary	Change in diffusing capacity for carbon monoxide at 6 and 12 months	DLCO is a measurement of the of the lung's gas transfer ability.	6 and 12 months
Secondary	Change in 6-minute walk distance from baseline		12 months
Secondary	Change in Leicester cough questionnaire (LCQ) from baseline		12 months
Secondary	Change in King's Brief Interstitial Lung Disease Questionnaire (K-BILD) from baseline		12 months
Secondary	Change in Parent cough-specific quality of life (PCSQoL) from baseline		12 months