TELO-SCOPE study: a randomised, double-blind, placebo-controlled, phase 2 trial of danazol for short telomere related pulmonary fibrosis.

2021-12

Mackintosh, John A

Pietsch, Maria

Lutzky, Viviana

Enever, Debra

Bancroft, Sandra

Apte, Simon H

Tan, Maxine

Yerkovich, Stephanie T

Dickinson, Joanne L

Pickett, Hilda A

Selvadurai, Hiran

Grainge, Christopher

Goh, Nicole S L

Hopkins, Peter

Glaspole, Ian

Reynolds, Paul N

Wrobel, Jeremy

Jaffe, Adam

Corte, Tamera J

Chambers, Daniel C

interstitial fibrosis

Journal Article

0000-0002-5254-4144

10.1136/bmjresp-2021-001127

Recent discoveries have identified shortened telomeres and related mutations in people with pulmonary fibrosis (PF). There is evidence to suggest that androgens, including danazol, may be effective in lengthening telomeres in peripheral blood cells. This study aims to assess the safety and efficacy of danazol in adults and children with PF associated with telomere shortening. A multi-centre, double-blind, placebo-controlled, randomised trial of danazol will be conducted in subjects aged >5 years with PF associated with age-adjusted telomere length ≤10th centile measured by flow fluorescence in situ hybridisation; or in children, a diagnosis of dyskeratosis congenita. Adult participants will receive danazol 800 mg daily in two divided doses or identical placebo capsules orally for 12 months, in addition to standard of care (including pirfenidone or nintedanib). Paediatric participants will receive danazol 2 mg/kg/day orally in two divided doses or identical placebo for 6 months. If no side effects are encountered, the dose will be escalated to 4 mg/kg/day (maximum 800 mg daily) orally in two divided doses for a further 6 months. The primary outcome is change in absolute telomere length in base pairs, measured using the telomere shortest length assay (TeSLA), at 12 months in the intention to treat population. Ethics approval has been granted in Australia by the Metro South Human Research Ethics Committee (HREC/2020/QMS/66385). The study will be conducted and reported according to Standard Protocol Items: Recommendations for Interventional Trials guidelines. Results will be published in peer-reviewed journals and presented at international and national conferences. NCT04638517; Australian New Zealand Clinical Trials Registry (ACTRN12620001363976p).

link

BMJ Open Respiratory Research 2021; 8(1): e001127

BMJ Open Respiratory Research