Bedaquiline long-acting

Associated long-acting platforms

unknown, unknown

Administration route

Subcutaneous, Intramuscular

Therapeutic area(s)

Use case(s)

Use of drug

Dosage

Drug information

Delivery device(s)

Not provided

Scale-up prospects

Not provided

Tentative equipment list for manufacturing

Not provided

Manufacturing

Not provided

Specific analytical instrument required for characterization of formulation

Not provided

A Single Ascending Dose, Single-Centre Study, to Assess Pharmacokinetics, Safety and Tolerability of a Single Intramuscular Dose of Bedaquiline Long-Acting Injection Formulation in Healthy Participants

Identifier

EUCT 2023-508810-41-00

Link

https://euclinicaltrials.eu/ctis-public/view/2023-508810-41-00?lang=en

Phase

Phase I

Status

Recruiting

Sponsor

Janssen Cilag International

More details

Not provided

Purpose

Safety and Tolerability of a Single Intramuscular Dose of Bedaquiline Long-Acting Injection Formulation

Interventions

Intervention 1

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
2024-06-03 00:00:00

Actual Start Date
2024-07-02 00:00:00

Anticipated Date of Last Follow-up
Not provided

Estimated Primary Completion Date
Not provided

Estimated Completion Date
2026-02-17 00:00:00

Actual Primary Completion Date
Not provided

Actual Completion Date
Not provided

Studied populations

Age Cohort

• Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
Yes

Comments about the studied populations

study protocol code: TMC207TBC1006

Health status

Study type

Interventional (clinical trial)

Enrollment

Not provided

Allocation

Non-randomized

Intervention model

Not provided

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key results

Proprietary excipients used

Not provided

Novel excipients or existing excipients at a concentration above Inactive Ingredients Database (IID) for the specified route of administration

Not provided

Residual solvents used

Not provided

Compound patent families

Publications

Bedaquiline: what might the future hold? Shaw, Emily S et al., The Lancet Microbe, Volume 5, Issue 12, 100909

Tuberculosis drug development has stagnated for decades, so the recent availability of bedaquiline is welcome. Bedaquiline-containing regimens, now the first-line therapy recommended by WHO, have transformed the treatment of drug-resistant tuberculosis, offering safer and more effective oral treatment options. However, key obstacles need to be overcome to ensure global access and prevent the rapid development of resistance against this promising class of drugs. In this Personal View, building on an international workshop held in 2023, we evaluate the current evidence and suggest possible ways forward, recognising the tension between increasing use and slowing the rise of resistance. We also discuss problems in accessing bedaquiline-containing regimens, the potential widening of their use beyond drug-resistant tuberculosis, and lessons for utilising new drugs as they are developed.

Kaushik A, Ammerman NC, Tasneen R, Lachau-Durand S, Andries K, Nuermberger E. Efficacy of Long-Acting Bedaquiline Regimens in a Mouse Model of Tuberculosis Preventive Therapy. Am J Respir Crit Care Med. 2022;205(5):570-579. doi:10.1164/rccm.202012-4541OC

Rationale: Completion of preventive therapy is a major bottleneck in global tuberculosis control. Long-acting injectable drug formulations would shorten therapy administration and may thereby improve completion rates. Recently, a long-acting formulation of bedaquiline demonstrated antituberculosis activity for up to 12 weeks after injection in a validated mouse model of preventive therapy. Objectives: The objectives of this study were to 1) determine the total duration of activity after an injection of long-acting bedaquiline and 2) evaluate the activity of regimens comprised of long-acting bedaquiline plus short (2-4 wk) oral companion courses of bedaquiline, with or without rifapentine, using the validated mouse model of tuberculosis preventive therapy. Methods: After the establishment of a stable Mycobacterium tuberculosis lung infection in bacillus Calmette-Guérin (BCG)-immunized BALB/c mice, treatment was initiated with 1 of 12 randomly assigned regimens. In addition to positive and negative controls, six regimens included one or two injections of long-acting bedaquiline (alone or with oral bedaquiline with or without rifapentine), and four comparator regimens consisted of oral agents only. Lung bacterial burden was measured monthly for up to 28 weeks. Measurements and Main Results: One injection of long-acting bedaquiline at 160 mg/kg exerted antituberculosis activity for 12 weeks. Compared with the positive control (daily isoniazid-rifapentine for 4 wk), six regimens had equivalent bactericidal activity (including two all-oral comparator regimens), and two regimens had superior sterilizing activity: one injection with 2 weeks of oral bedaquiline and high-dose rifapentine; and two injections with 4 weeks of oral bedaquiline. Conclusions: Long-acting injectable bedaquiline has significant potential for shortening tuberculosis preventive therapy.

Ammerman NC, Nuermberger EL, Owen A, Rannard SP, Meyers CF, Swindells S. Potential Impact of Long-Acting Products on the Control of Tuberculosis: Preclinical Advancements and Translational Tools in Preventive Treatment. Clin Infect Dis. 2022 Nov 21;75(Suppl 4):S510-S516. doi: 10.1093/cid/ciac672. PMID: 36410384; PMCID: PMC10200320.

A key component of global tuberculosis (TB) control is the treatment of latent TB infection. The use of long-acting technologies to administer TB preventive treatment has the potential to significantly improve the delivery and impact of this important public health intervention. For example, an ideal long-acting treatment could consist of a single dose that could be administered in the clinic (ie, a “1-shot cure” for latent TB). Interest in long-acting formulations for TB preventive therapy has gained considerable traction in recent years. This article presents an overview of the specific considerations and current preclinical advancements relevant for the development of long-acting technologies of TB drugs for treatment of latent infection, including attributes of target product profiles, suitability of drugs for long-acting formulations, ongoing research efforts, and translation to clinical studies.

Kaushik A, Ammerman NC, Tyagi S, Saini V, Vervoort I, Lachau-Durand S, Nuermberger E, Andries K. Activity of a Long-Acting Injectable Bedaquiline Formulation in a Paucibacillary Mouse Model of Latent Tuberculosis Infection. Antimicrob Agents Chemother. 2019 Mar 27;63(4):e00007-19. doi: 10.1128/AAC.00007-19. PMID: 30745396; PMCID: PMC6437534.

The potent antituberculosis activity and long half-life of bedaquiline make it an attractive candidate for use in long-acting/extended-release formulations for the treatment of latent tuberculosis infection (LTBI). Our objective was to evaluate a long-acting injectable (LAI) bedaquiline formulation in a validated paucibacillary mouse model of LTBI.

Additional documents

• RespiriTB announces the start of a Phase 1 clinical trial with bedaquiline long- acting injectable

Useful links

• Excitement builds for long-acting TB treatments, but research still at early stage

• Are long-acting injectables the future of TB treatment?

• A Single Ascending Dose, Single-Centre Study, to Assess Pharmacokinetics, Safety and Tolerability of a Single Intramuscular Dose of Bedaquiline Long-Acting Injection Formulation in Healthy Participant

	Collaborate for development Consider on a case by case basis, collaborating on developing long acting products with potential significant public health impact, especially for low- and middle-income countries (LMICs), utilising the referred to long-acting technology Not provided
	Share technical information for match-making assessment Provide necessary technical information to a potential partner, under confidentiality agreement, to enable preliminary assessment of whether specific medicines of public health importance in LMICs might be compatible with the referred to long-acting technology to achieve a public health benefit Not provided
	Work with MPP to expand access in LMICs In the event that a product using the referred to long-acting technology is successfully developed, the technology IP holder(s) will work with the Medicines Patent Pool towards putting in place the most appropriate strategy for timely and affordable access in low and middle-income countries, including through licensing Not provided

Not provided