Clinical Trials Register

Summary
EudraCT Number:	2020-004444-29
Sponsor's Protocol Code Number:	RID-TB:Treat
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2020-09-17
Trial 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

2020-004444-29

A.3

Full title of the trial

An open-label, multi-centre, randomised controlled trial evaluating the effects of short-course rifapentine-based regimens and additional adherence support on LTBI treatment adherence and completion among adults in the UK

A.3.1

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

Research to Improve the Detection and Treatment of Latent Tuberculosis Infection: Treatment

A.3.2

Name or abbreviated title of the trial where available

RID-TB:Treat

A.4.1

Sponsor's protocol code number

RID-TB:Treat

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	University College London
B.1.3.4	Country	United Kingdom
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	MRC Clinical Trials Unit at UCL
B.5.2	Functional name of contact point	Clinical Trials Manager
B.5.3	Address:
B.5.3.1	Street Address	90 High Holborn 2nd Floor
B.5.3.2	Town/ city	London
B.5.3.3	Post code	WC1V 6LJ
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	02076704619
B.5.5	Fax number	20276704814
B.5.6	E-mail	mrcctu.rid-tb@ucl.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	Rifapentine
D.2.1.1.2	Name of the Marketing Authorisation holder	Sanofi
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	Rifapentine
D.3.2	Product code	N/A
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.3.9.4	EV Substance Code	AS1
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

Latent Tuberculosis infection (LTBI)

E.1.1.1

Medical condition in easily understood language

Latent TB is where people have been infected with the bacteria that cause TB, but do not have symptoms. It may develop into "active" TB where the person becomes unwell and can pass on the infection.

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10065048
E.1.2	Term	Latent tuberculosis
E.1.2	System Organ Class	10021881 - Infections and infestations

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

There are two primary hypotheses:
• The novel short course rifapentine-based regimens 3HP and 1HP improve treatment adherence compared to 3HR
• Additional adherence support improves adherence to each treatment regimen compared to routine support

E.2.2

Secondary objectives of the trial

• Proportion of doses missed over the treatment period
• Proportion of pills missed over the treatment period
• Taking at least 90% of doses and pills over the treatment period
• Early study treatment discontinuation for any reason
• Permanently stopping study treatment due to drug-related adverse event
• Grade ≥3 adverse events
• Adverse events at least possibly associated with study treatment
• Development of active TB within 12 months of starting treatment

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

1. Process evaluation of the adherence intervention
Date, title are the same as main protocol
1.1. Intervention acceptability
A sample of participants will be interviewed based on their treatment adherence in WP3 for each intervention arm (10 participants per arm: 5 high adherence, 5 low adherence; total 60 interviews) for a qualitative assessment of participant acceptability of the intervention. Participants will be consented to this follow-up at the start of the treatment intervention trial, creating a cohort of participants who are willing to be approached for intervention acceptability interviews after completing the study.)

We will also conduct brief semi-structured interviews (in person or by phone) with a purposive sample of 20 service providers to obtain feedback on the delivery of the intervention and to identify any issues that might enhance delivery in practice and to assess wider contextual issues impacting on delivery.

1.2. Intervention fidelity
Health care professionals responsible for administering the interventions will be requested to complete a short checklist form following patient randomisation in order to assess intervention fidelity. This will confirm whether each component of the interventions was delivered per protocol (e.g. whether information about treatment frequency and duration was provided; whether Wisepill EveriMed reminders were set up for patients allocated to receive additional adherence support). The form will also record the job role of the person administering the interventions and summary reasons for any protocol deviations.

1.3. Process evaluation
Process evaluation will follow MRC guidance using an embedded, mixed-methods evaluation approach. Process evaluation will be conducted by the research team, working closely with the Intervention Development Group (IDG) and clinicians delivering the trial. We will encourage implementing clinicians to report major issues that might compromise delivery of the trial, during the trial, rather than waiting for a formal interview on trial completion.

The Trial Management Group will develop plans to integrate process and outcomes data and develop communication strategies to minimise duplication and conflict between process and outcome evaluation. We will clearly describe the intervention and clarify causal assumptions (e.g. support materials will facilitate testing and treatment by correcting misconceptions about LTBI and LTBI testing and treatment, and concerns about them). We will verify causal assumptions using validated measures of illness perceptions (bIPQ), treatment beliefs (BMQ-treatment) at baseline, week 2, and treatment competion (questionnaire administration in line with visits for clinical monitoring). This will assess processes within the trial by examining relationships between process variables and outcomes, and provide insights on the mechanisms of the intervention by testing hypothesised causal pathways.

2. Health Economic evaluation
Health Economic evaluation will be undertaken as part of Work package 4 of the RID-TB programme. Workpackage 4 and will employ economic analysis to calculate if changes to diagnosis and/or treatment offer value for money. An integrated transmission-dynamic health-economic model will synthesise data obtained within the entire RID-TB programme and evidence from sources including the scientific literature, census data and life-tables from national statistics, LTBI/TB screening and TB surveillance data. The model will consider different age-groups, and different social/ethnic groups, subdivided into UK-born and foreign-born individuals, which can differ in their size, age-structure, rates of migration, rates of occurrence of latent and active TB, and in the patterns of social mixing within and between different groups that affect TB transmission rates. This will allow estimation of the long-term, national-level benefits of the studied interventions. Participants will be asked to co

E.3

Principal inclusion criteria

1. Aged ≥16 years to ≤65 at screening
2. LTBI diagnosis defined on the basis of all of the following:
(a) a positive result on an Interferon Gamma Release Assay (IGRA), Tuberculin Skin Test (TST) or C-Tb skin test and
(b) negative TB symptoms at screening and
(c) no signs of active TB on a Chest X-ray
3. Eligible for LTBI treatment at TB clinics and national LTBI screening services based on NICE guidelines, which means having one or more of the following :
• Recent infection (contact tracing);
• New entrants at risk (i.e., those that immigrated < 5 years from countries with a high incidence of TB, which is defined as ≥ 40 cases/100,000 population); or
• Individuals who are assessed in the TB clinic for latent TB testing, or have been referred for treatment following testing by specialities or departments within primary or secondary care settings
4. Agree to LTBI treatment
5. Willing and able to provide written informed consent

E.4

Principal exclusion criteria

1. Patients weighing < 30 kg.
2. Need for medications that cannot be safely taken together with study drugs
3. Any medical condition deserving priority of treatment (such as: porphyria, malabsorption syndromes, Clostridium difficile-Associated Diarrhoea and other conditions)
4. History of sensitivity/intolerance to isoniazid or rifamycins
5. Individuals with documented liver disease, defined as:
• LFT (ALT/AST/bilirubin) over three times upper limit of normal (ULN) at baseline. This reflects normal clinical practice. For patientparticipant safety, liver function tests are carried on a regular basis. One abnormal value prevents the patient from participating on the study.
• Clinical diagnosis of cirrhosis (jaundice, hematemesis, ascites or previous episodes of liver encephalopathy),
• HbsAg positive or HCV antibody positive and deemed ineligible for LTBI treatment by the clinician
6. Intending to move outside of the treatment locality within 20 weeks of starting treatment
7. Individuals who would usually be offered LTBI treatment under Directly Observed Therapy (DOT) as part of enhanced case management in complex cases such as those from under-served groups (such as people who are homeless, misuse substances, have been in prison or who are vulnerable migrants).
8. Use of another experimental investigational medicinal product that is likely to interfere with the study medication within 3 months of study enrolment.
9. Women who are breastfeeding, pregnant, or of childbearing potential* who do not agree to use an effective method of contraception from the time consent is signed until 4 weeks after treatment discontinuation or completion.
10. Women of child bearing potential without a negative urine pregnancy test within 7 days prior to being registered for trial treatment.

E.5 End points

E.5.1

Primary end point(s)

Adequate treatment adherence, defined as taking ≥ 90% of allotted doses within allowable time-frame specified by regimen

E.5.1.1

Timepoint(s) of evaluation of this end point

All participants will reach the end of diagnostic follow up 20 weeks after randomisation.

E.5.2

Secondary end point(s)

• Proportion of doses missed over the treatment period
• Proportion of pills missed over the treatment period
• Early study treatment discontinuation for any reason
• Permanently stopping study treatment due to drug-related adverse event
• Grade ≥3 adverse events
• Adverse events associated with study treatment
• Development of active TB within 12 months of starting treatment

E.5.2.1

Timepoint(s) of evaluation of this end point

The following end points will be evaluated at the end of folllow-up or at the time of event during follow-up period: Proportion of doses missed over the treatment period; Proportion of pills missed over the treatment period; Early study treatment discontinuation for any reason; Permanently stopping study treatment due to drug-related adverse event; Grade ≥3 adverse events; Adverse events associated with study treatment. For participants who become pregnant during treatment and within one week of their last dose, pregnancy outcomes will be collected using registry data held by NHS Digital and/or Public Health England.
Development of active TB within 12 months of starting treatment will be evaluated.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

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

Yes

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)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

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)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in 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

The trial will close when all participants have completed follow-up, record linkage to ascertain TB has been finished, and after the trial database is locked, which is anticipated to be within 3 months after information on primary and secondary outcomes has been collected. It is anticipated that the overall duration of the trial will be approximately 3 years.

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