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

NCT04638517 | Terminated Phase 2

• 1 other identifier: TELO-SCOPE
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 9

Brief 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.

Conditions

Pulmonary Fibrosis; Telomere Shortening; Telomere Disease; Dyskeratosis Congenita

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• 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

  6 and 12 months

• Change in diffusing capacity for carbon monoxide at 6 and 12 months

  6 and 12 months

Study Arms (2)

Danazol

ACTIVE COMPARATOR

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

Placebo

PLACEBO COMPARATOR

Matching placebo capsules.

Drug: Placebo

Interventions

Danazol DRUG

Danazol up to 800mg daily in two-divided doses.

Danazol

Placebo DRUG

Matching placebo.

Placebo

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females aged \>5 years, able to take capsules orally.
• 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.
• Age-adjusted peripheral blood leukocyte telomere length \< 10th centile on Flow-FISH.
• FVC \> 40% predicted.
• DLCO \> 25% predicted.
• If receiving background pirfenidone / nintedanib, stable dose for 28 days prior to screening.
• Able to understand and sign a written informed consent form (or legally authorised representative).
• 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).

You may not qualify if:

• Actively or imminently listed for lung transplantation.
• Undergone, awaiting, or likely to require bone marrow transplantation within 12 months.
• Concurrent enrolment in another study.
• Females with a positive pregnancy test at screening or currently breastfeeding.
• Pelvic infection.
• Past jaundice with oral contraceptives.
• Undiagnosed abnormal genital bleeding.
• Undiagnosed ovarian/uterine masses
• Any history of malignancy likely to result in significant disability or likely to require significant medical or surgical intervention within the next 12 months.
• History of androgen-dependent tumour.
• 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.
• History of end-stage liver disease or ALT or AST \> 3 times the upper limit of normal.
• History of end-stage kidney disease requiring dialysis.
• Markedly impaired cardiac function.
• Known increased risk of or history of thromboembolism (e.g. Factor V Leiden, Protein C or S deficiency).

Sponsors & Collaborators

• The University of Queensland: lead

Study Sites (9)

John Hunter Hospital

Newcastle, New South Wales, 2305, Australia

Location

Sydney Children's Hospital

Sydney, New South Wales, 2031, Australia

Location

Royal Prince Alfred Hospital

Sydney, New South Wales, 2050, Australia

Location

The Children's Hospital Westmead

Sydney, New South Wales, 2145, Australia

Location

The Prince Charles Hospital

Brisbane, Queensland, 4032, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

The Alfred

Melbourne, Victoria, 3004, Australia

Location

The Austin

Melbourne, Victoria, 3084, Australia

Location

Fiona Stanley Hospital

Perth, Western Australia, 6150, Australia

Location

Related Publications (1)

• 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.

  PMID: 34857525 DERIVED

MeSH Terms

Conditions

Pulmonary Fibrosis; Dyskeratosis Congenita

Interventions

Danazol

Condition Hierarchy (Ancestors)

Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Congenital Bone Marrow Failure Syndromes; Bone Marrow Failure Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Skin Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Skin Diseases, Genetic; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2020
• First Posted: November 20, 2020
• Study Start: September 7, 2021
• Primary Completion: January 16, 2025
• Study Completion: January 16, 2025
• Last Updated: August 5, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share

Locations

AU (9)