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

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.

Study Overview

• Status: Terminated
• Conditions: Pulmonary Fibrosis; Dyskeratosis Congenita; Telomere Shortening; Telomere Disease
• Intervention / Treatment: Drug: Danazol; Drug: Placebo

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Newcastle, New South Wales, Australia, 2305
      • John Hunter Hospital
    • Sydney, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
    • Sydney, New South Wales, Australia, 2031
      • Sydney Children's Hospital
    • Sydney, New South Wales, Australia, 2145
      • The Children's Hospital Westmead
  • Queensland
    • Brisbane, Queensland, Australia, 4032
      • The Prince Charles Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • The Alfred
    • Melbourne, Victoria, Australia, 3084
      • The Austin
  • Western Australia
    • Perth, Western Australia, Australia, 6150
      • Fiona Stanley Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Danazol; 800mg daily in two divided doses orally for 12 months. In subjects who have difficulty tolerating danazol / placebo, the dose will be reduced by 200mg/day and side effects will be reassessed. If symptoms related to the study drug persist, subsequent 200mg/day dose reductions will be allowed until a tolerated dose is achieved. Background antifibrotic therapy is allowed.	Drug: Danazol; Danazol up to 800mg daily in two-divided doses.
Placebo Comparator: Placebo; Matching placebo capsules.	Drug: Placebo; Matching placebo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-emergent adverse events		12 months
Number of Participants With Death or Non-Elective Hospitalisation		12 months
Change in telomere length from baseline to 3, 6 and 9 months (base pairs)		3, 6 and 9 months
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
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
Change in 6-minute walk distance from baseline		12 months
Change in Leicester cough questionnaire (LCQ) from baseline		12 months
Change in King's Brief Interstitial Lung Disease Questionnaire (K-BILD) from baseline		12 months
Change in Parent cough-specific quality of life (PCSQoL) from baseline		12 months

Collaborators and Investigators

• Sponsor: The University of Queensland

Publications and helpful links

General Publications

• Mackintosh JA, Pietsch M, Lutzky V, Enever D, Bancroft S, Apte SH, Tan M, Yerkovich ST, Dickinson JL, Pickett HA, Selvadurai H, Grainge C, Goh NS, Hopkins P, Glaspole I, Reynolds PN, Wrobel J, Jaffe A, Corte TJ, Chambers DC. TELO-SCOPE study: a randomised, double-blind, placebo-controlled, phase 2 trial of danazol for short telomere related pulmonary fibrosis. BMJ Open Respir Res. 2021 Dec;8(1):e001127. doi: 10.1136/bmjresp-2021-001127.

Study record dates

Study Major Dates

• Study Start (Actual): September 7, 2021
• Primary Completion (Actual): January 16, 2025
• Study Completion (Actual): January 16, 2025

Study Registration Dates

• First Submitted: November 4, 2020
• First Submitted That Met QC Criteria: November 15, 2020
• First Posted (Actual): November 20, 2020

Study Record Updates

• Last Update Posted (Actual): August 5, 2025
• Last Update Submitted That Met QC Criteria: July 31, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Congenital Bone Marrow Failure Syndromes; Bone Marrow Failure Disorders; Pathologic Processes; Genetic Diseases, Inborn; Respiratory Tract Diseases; Lung Diseases; Hematologic Diseases; Skin Diseases; Congenital Abnormalities; Bone Marrow Diseases; Lung Diseases, Interstitial; Skin Diseases, Genetic; Genetic Diseases, X-Linked; Skin Abnormalities; Pulmonary Fibrosis; Fibrosis; Dyskeratosis Congenita; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Estrogen Antagonists; Danazol
• Other Study ID Numbers: TELO-SCOPE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified data will be analysed and shared with collaborators with the plan to publish the results.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No