Clinical Trials Register

Summary
EudraCT Number:	2019-000580-24
Sponsor's Protocol Code Number:
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2019-03-25
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2019-000580-24

A.3

Full title of the trial

A single arm, open-label clinical trial of azithromycin in pulmonary sarcoidosis

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A clinical trial of the antibiotic azithromycin for patients with sarcoidosis

A.3.2

Name or abbreviated title of the trial where available

Azithromycin for sarcoidosis

A.4.1

Sponsor's protocol code number

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Hull & East Yorkshire Hospitals NHS trust
B.1.3.4	Country
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	SarcoidosisUK
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Hull York Medical School/ University of Hull
B.5.2	Functional name of contact point	Dr Simon Hart
B.5.3	Address:
B.5.3.1	Street Address	Academic Respiratory Medicine
B.5.3.2	Town/ city	Castle Hill Hospital
B.5.3.3	Post code	HU16 5JQ
B.5.4	Telephone number	01482624067
B.5.6	E-mail	s.hart@hull.ac.uk

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Azithromycin
D.2.1.1.2	Name of the Marketing Authorisation holder	Sandoz Ltd
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Azithromycin
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	azithromycin monohydrate
D.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	250
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Sarcoidosis

E.1.1.1

Medical condition in easily understood language

Sarcoidosis is a chronic inflammatory disease of unknown cause that commonly affects the lungs, lymph nodes, eyes, and skin, and sometimes the bones, heart and nervous system.

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Assess the effect of azithromycin on cough measured using automated cough counting

E.2.2

Secondary objectives of the trial

Assess the effect of azithromycin on :
• Cough visual analogue score (VAS)
• Leicester cough questionnaire (LCQ)
• King’s Sarcoidosis Questionnaire (KSQ)
• Clinical measurement as part of NHS care in the Sarcoidosis clinic over the study period will be recorded. Spirometry, chest x-ray, serum ACE, CRP are routinely measured. Progressive disease requiring escalation of therapy with steroids will be determined in the standard way by clinical MDT consensus.
• Exploratory variables in blood samples:
a) Anti-inflammatory activity of azithromycin assessed by cytokine release in an ex vivo whole blood assay
b) Engagement of drug with target by measuring mTOR activation in peripheral blood mononuclear cells.
• Variability of outcomes described above to inform statistical power calculations and determine sample size for a future RCT
• Feasibility assessment for a multicentre trial of long term azithromycin therapy in sarcoidosis by measuring screening success rates, recruitment, attrition, an

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Males or females, of any race, between 18 and 80 years of age, inclusive;
2. Able to speak, read, and understand English;
3. Able to provide written informed consent;
4. Able to communicate effectively with the Investigator and other study centre personnel and agree to comply with the study procedures and restrictions.
5. Clinician diagnosis of pulmonary sarcoidosis;
6. If a female of child-bearing potential (i.e., have not undergone a hysterectomy or bilateral oophorectomy) or not post-menopausal (defined as no menses for at least 12 months), agree to use acceptable birth control (defined in Section 6.3) from screening through to the follow up visit;

E.4

Principal exclusion criteria

1. Hypersensitivity to azithromycin or another macrolide antibiotic (e.g. erythromycin, clarithromycin) or excipients
2. History of signficant cardiac arrhythmia
3. Personal or family history of congenital long QT syndrome;
4. Prolonged QTc interval on 12–lead ECG
5. Severe liver disease
6. Evidence of acute bacterial infection
7. Clinically significant bronchiectasis
8. Requiring concomitant therapy with prohibited medications (see Section 7.5)
9. Pregnant or breastfeeding;
10. Treatment with an investigational drug or biologic within 30 days preceding the first dose of study medication or plans to take another investigational drug or biologic within 30 days of study completion;
11. Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the Investigator or Sponsor, would make the subject inappropriate for entry into this trial.

E.5 End points

E.5.1

Primary end point(s)

Cough assessed by:

- Hull Automated Cough Counter (HACC) with the Leicester software algorithm

Coughs will be counted over a 24-hour period after visits 1,2, and 3 using a digital portable cough counter that has been shown to be reliable and reproducible in counting coughs in a variety of conditions and settings. This cough counter discriminates cough from other sounds by analysing cough sounds acoustically. The cough counter will be returned or collected for analysis following visits 1, 2, and 3.

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline, 1 month, 3 months

E.5.2

Secondary end point(s)

Cough visual analogue score (VAS)
Leicester cough questionnaire (LCQ).
King’s Sarcoidosis Questionnaire (KSQ)
Clinical measurement as part of NHS care in the Sarcoidosis clinic over the study period will be recorded. Spirometry, chest x-ray, serum ACE, CRP are routinely measured. Progressive disease requiring escalation of therapy with steroids will be determined in the standard way by clinical MDT consensus.
Blood will be analysed for exploratory variables:
a) Anti-inflammatory activity of azithromycin assessed by cytokine release in an ex vivo whole blood assay
b) Engagement of drug with target by measuring mTOR activation in peripheral blood mononuclear cells.
•Variability of outcomes described above to inform statistical power calculations and determine sample size for a future RCT
•Feasibility assessment for a multicentre trial of long term azithromycin therapy in sarcoidosis by measuring screening success rates, recruitment, attrition, and data quality.

E.5.2.1

Timepoint(s) of evaluation of this end point

Baseline, 1 month, 3 months

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1