Using Danazol to Improve Health Outcomes in Pulmonary Fibrosis

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

This study is testing if the medication danazol can help improve health for people with pulmonary fibrosis who have short telomeres.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 5 Years and up
• Sex: All
• Sponsor: The University of Queensland (Academic / other)
• Locations: 9 sites (Newcastle, New South Wales and 8 other locations)
• Trial ID: NCT04638517 on ClinicalTrials.gov

What this trial studies

TELO-SCOPE is a national, multi-centre, double-blind, placebo-controlled, randomised trial aimed at evaluating the safety and efficacy of danazol in reducing telomere attrition in patients with pulmonary fibrosis associated with short telomeres. Participants aged over 5 years with a diagnosis of pulmonary fibrosis and specific telomere length criteria will be enrolled and randomly assigned to receive either danazol or a placebo for 12 months. The primary outcome measure will be the change in telomere length after the treatment period. This study seeks to determine if adding danazol to standard care can improve health outcomes for these patients.

Who should consider this trial

Good fit: Ideal candidates include males and females over 5 years old with specific types of pulmonary fibrosis and short telomere lengths.

Not a fit: Patients who are actively listed for lung transplantation or have undergone recent lung surgery may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved health outcomes and potentially slower disease progression for patients with pulmonary fibrosis.

How similar studies have performed: While the approach of using danazol for telomere-related conditions is novel, similar studies targeting telomere shortening have shown promise in other contexts.

Eligibility criteria

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).

Where this trial is running

Newcastle, New South Wales and 8 other locations

• John Hunter Hospital — Newcastle, New South Wales, Australia (Recruiting)
• Sydney Children's Hospital — Sydney, New South Wales, Australia (Not_yet_recruiting)
• Royal Prince Alfred Hospital — Sydney, New South Wales, Australia (Recruiting)
• The Children's Hospital Westmead — Sydney, New South Wales, Australia (Not_yet_recruiting)
• The Prince Charles Hospital — Brisbane, Queensland, Australia (Recruiting)
• Royal Adelaide Hospital — Adelaide, South Australia, Australia (Recruiting)
• The Alfred — Melbourne, Victoria, Australia (Recruiting)
• The Austin — Melbourne, Victoria, Australia (Recruiting)
• Fiona Stanley Hospital — Perth, Western Australia, Australia (Recruiting)

Study contacts

• Study coordinator: Daniel Chambers

Conditions Pulmonary Fibrosis; Telomere Shortening; Telomere Disease; Dyskeratosis Congenita