Safety and Efficacy Study of Intracystic TARA-002 for the Treatment of Lymphatic Malformations in Participants 6 Months to Less Than 18 Years of Age

Study Overview
=================
Brief Summary
-----------------
This is a Phase 2a/b single arm open label study to evaluate the safety, reactogenicity, and efficacy of intracystic injection of TARA-002 in participants 6 months to less than 18 years of age for the treatment of macrocystic and mixed cystic lymphatic malformations. The Phase 2a safety lead-in, age de-escalation study is designed to establish the safety of TARA-002 in older participants 6 years to less than 18 years before proceeding to younger participants 2 years to less than 6 years, then 6 months to less than 2 years. The Phase 2b is an expansion study in which enrollment of participants will be initiated after safety has been established in each cohort during the Phase 2a safety lead-in study. Each participant will receive up to 4 injections of TARA-002 spaced approximately 6 weeks apart.

Official Title
-----------------
A Phase 2a/b Single Arm Open Label Study to Evaluate the Safety and Efficacy of Intracystic Administration of TARA-002 in Participants Between 6 Months to Less Than 18 Years of Age for the Treatment of Macrocystic and Mixed Cystic Lymphatic Malformations

Conditions
-----------------
Lymphatic Malformation

Intervention / Treatment
-----------------
* Biological: TARA-002


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female participants 6 months to less than 18 years of age at the time of informed consent/assent form was signed Participants whose parent/LAR(s) have voluntarily given written consent and participants who provided assent (if applicable) after the study has been explained to them Participants with macrocystic LM or mixed cystic LM (≥ 50% macrocystic disease measured by volume) of the Head/Neck/Mediastinum according to the ISSVA 2018 criteria (ISSVA 2018) measured via LM imaging at Screening to confirm, upon central review, the diagnosis of macrocystic or mixed cystic LM Participants who may have had surgical or sclerotherapy treatment for their LM, but not within six months of the consent/assent form being signed Exclusion Criteria: Penicillin allergy Vascular tumors or combined vascular malformations Microcystic LM or mixed cystic LM with predominant microcystic features LMs of the orbit (orbital LM) as target cyst For more information on eligibility criteria, please contact the sponsor.

Ages Eligible for Study
-----------------
Minimum Age: 6 Months
Maximum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TARA-002<br>TARA-002 is a lyophilized biological preparation for injection containing cells of Streptococcus pyogenes (Group A, type 3) Su strain treated with benzylpenicillin. | Biological: TARA-002<br>* All participants will receive up to 4 intracystic injections spaced approximately 6 weeks apart.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with clinical success after one treatment cycle of TARA-002 |  | 8 weeks after the last injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Percentage of participants with solicited local site and systemic reactions |  | 14 days (2 weeks) after each injection | 
| Safety: Percentage of participants with unsolicited adverse events (AEs) |  | Through study completion (approximately 32 weeks after last injection) | 
| Safety: Percentage of participants with SAEs, AEs of special interest, AEs leading to premature discontinuation of study intervention, AEs leading to withdrawal from study, AEs with an outcome of death, and MAAEs |  | Through study completion (approximately 32 weeks after last injection) | 
| Durable Response: Proportion of participants with clinical success after one treatment cycle of TARA-002 assessed at 8 weeks after the last injection and maintained clinical success at 32 weeks after the last injection |  | 32 weeks after the last injection | 
| Clinical Success by LM Type: Proportion of participants with macrocystic LM or mixed cystic LM with clinical success after one treatment cycle of TARA-002 |  | 8 weeks after the last injection | 
| Investigator Assessment: Proportion of participants who demonstrate clinical improvement, as assessed by the Investigator, after one treatment cycle of TARA-002 compared to baseline |  | 8 weeks after last injection and 32 weeks after last injection | 
| Quality of Life: Change in Quality-of-Life assessment based on Pediatric Quality of Life Inventory (PedsQL) and Visual Analog Scale (VAS) for Pain after one treatment cycle of TARA-002 |  | 8 weeks after last injection and 32 weeks after last injection | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Macrocystic lymphatic malformations, Mixed-cystic lymphatic malformations