Approval Probability
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Also known as apazunersen
GTX-102 · 4 trials · 1 indication
The following assessments will be included to calculate the MDRI net response: Bayley-4 Cognitive and Receptive Communication, Aberrant Behavior Checklist- Community (ABC-C) Hyperactivity/Noncompliance (H/N), Angelman Severity Assessment (ASA) Sleep, ASA Gross Motor. For each assessment a meaningful score difference (MSD) is defined. A single net response score per participant will be derived accordingly, and a summary measure of net response will then be calculated across all participants.
The following assessments will be included to calculate the MDRI net response: Vineland-3 Expressive and Receptive Communication, ABC-C Irritability, ASA Gross Motor. For each assessment a meaningful score difference (MSD) is defined. A single net response score per participant will be derived accordingly, and a summary measure of net response will then be calculated across all participants.
| Arm | Type | Description |
|---|---|---|
| GTX-102 | EXPERIMENTAL | Participants will receive GTX-102 via lumbar puncture (LP) during both the double-blind and open-label period |
| Sham-LP then GTX-102 | SHAM_COMPARATOR | Participants will receive sham procedure during the double-blind period and then will receive GTX-102 via LP during the open-label period |
| Subprotocol A GTX-102 | EXPERIMENTAL | Participants with deletion-type Angelman syndrome, ≥1 to \<4 years of age will receive increasing doses of GTX-102 via intrathecal (IT) injection until the target dose is achieved. Dosing occurs every 3 months (Q3M) thereafter. |
| Subprotocol B GTX-102 | EXPERIMENTAL | Participants with paternal uniparental disomy (UPD)/imprinting center defect (ICD) Angelman syndrome, ≥4 to \<18 years of age will receive increasing doses of GTX-102 via IT injection until the target dose is achieved. Dosing occurs Q3M thereafter. |
| Subprotocol C GTX-102 | EXPERIMENTAL | Participants with all genotypes of Angelman syndrome, ≥18 to \<65 years of age will receive increasing doses of GTX-102 via IT injection until the target dose is achieved. Dosing occurs Q3M thereafter. |
| Subprotocol D GTX-102 | EXPERIMENTAL | Participants with mutation-type Angelman syndrome, ≥4 to \<18 years of age will receive increasing doses of GTX-102 via IT injection until the target dose is achieved. Dosing occurs Q3M thereafter. |
| Subprotocol D No Intervention then GTX-102 | EXPERIMENTAL | Participants with mutation-type Angelman syndrome, ≥4 to \<18 years of age will receive no treatment during the initial period. At the end of the no treatment period, participants will receive increasing doses of GTX-102 via IT injection until the target dose is achieved. Dosing occurs Q3M thereafter. |
| GTX-102 Cohort 1 | EXPERIMENTAL | 3.3 mg starting dose followed by intra-patient dose escalation up to 36 mg and then a maintenance phase (in U.S participants 4 to \<17 years of age) |
| GTX-102 Cohort 2 | EXPERIMENTAL | 10 mg starting dose followed by intra-patient dose escalation up to 36 mg and then a maintenance phase (in U.S participants 4 to \<17 years of age) |
| GTX-102 Cohort 3 | EXPERIMENTAL | 20 mg starting dose followed by intra-patient dose escalation up to 55 mg and then a maintenance phase (in U.S participants 4 to \<17 years of age) |
| GTX-102 Cohort 4 | EXPERIMENTAL | 3.3 mg starting dose followed by slow intra-patient dose escalation up to 5 mg and then a maintenance phase (in Ex-U.S participants 4 to \<8 years of age) |
| GTX-102 Cohort 5 | EXPERIMENTAL | 5 mg starting dose followed by slow intra-patient dose escalation up to 7.5 mg and then a maintenance phase (in Ex-U.S participants ≥ 8 to 17 years of age) |
| GTX-102 Cohort 6 | EXPERIMENTAL | 7.5 mg starting dose followed by slow intra-patient dose escalation up to 10 mg and then a maintenance phase (in Ex-U.S participants 4 to \<8 years of age) |
| GTX-102 Cohort 7 | EXPERIMENTAL | 10 mg starting dose followed by slow intra-patient dose escalation up to 12 mg and then a maintenance phase (in Ex-U.S participants ≥ 8 to 17 years of age) |
| GTX-102 Cohort US | EXPERIMENTAL | 2 mg for 4 monthly doses followed by a quarterly maintenance regimen |
| GTX-102 Expanded Enrollment Cohort A | EXPERIMENTAL | Sponsor selected dose followed by slow intra-patient dose escalation and then a maintenance phase (in Ex-U.S participants 4 to \<8 years of age) |
| GTX-102 Expanded Enrollment Cohort B | EXPERIMENTAL | Sponsor selected dose followed by slow intra-patient dose escalation and then a maintenance phase (in Ex-U.S participants ≥ 8 to 17 years of age) |
| GTX-102 Expanded Enrollment Cohort C | EXPERIMENTAL | Sponsor selected dose followed by slow intra-patient dose escalation and then a maintenance phase (in U.S participants 4 to \<8 years of age) |
| GTX-102 Expanded Enrollment Cohort D | EXPERIMENTAL | Sponsor selected dose followed by slow intra-patient dose escalation and then a maintenance phase (in U.S participants ≥ 8 to 17 years of age) |
| GTX-102 Cohort E | EXPERIMENTAL | Sponsor selected dose followed by slow intra-patient dose escalation and then a maintenance phase (in participants that transition from GTX-102 US Cohort only) |
| Name | Type | Description |
|---|---|---|
| GTX-102 | DRUG | antisense oligonucleotide |
| Sham-LP | PROCEDURE | Small needle prick on the lower back at the location where the LP injection is normally made |
| No intervention | OTHER | During the no treatment period participants do not receive any study drug |
Key Inclusion Criteria: * Signed informed consent from parent(s) or legal guardian(s) * Confirmed diagnosis of AS with genetic confirmation of full maternal ubiquitin-protein ligase E3A (UBE3A) gene deletion causing AS in the region of 15q11.2 q13 * Able to ambulate independently, or with assistanc...
GTX-102 is an investigational therapy being developed for Angelman Syndrome, a rare neurogenetic disorder. It is designed to address the underlying genetic cause of the condition. Ultragenyx Pharmaceutical Inc. is evaluating GTX-102 in clinical trials that include pediatric and adult patients with both deletion and nondeletion types of Angelman Syndrome.
GTX-102 targets UBE3A-AS, the antisense transcript of the UBE3A gene. In Angelman Syndrome, the paternal copy of UBE3A is normally silenced by this antisense transcript. By targeting UBE3A-AS, GTX-102 aims to unsilence the paternal UBE3A allele and restore production of the UBE3A protein in the central nervous system.
GTX-102 is being developed by Ultragenyx Pharmaceutical Inc., a biopharmaceutical company focused on rare and ultrarare genetic diseases. Ultragenyx trades on the Nasdaq under the ticker symbol RARE. The company is the sponsor of the clinical development program for GTX-102 in Angelman Syndrome.
GTX-102 is in Phase 3 clinical development for Angelman Syndrome. The program includes a completed Phase 1 safety and tolerability study, a Phase 2 safety and efficacy study, a Phase 3 efficacy and safety study in pediatric subjects, and a Phase 3 long-term extension study. GTX-102 has received Breakthrough Therapy designation from the FDA.
GTX-102 has been studied in four clinical trials. These include NCT04259281, a completed Phase 1 safety and tolerability study; NCT07157254, a Phase 2 study in deletion and nondeletion Angelman Syndrome; NCT06617429, a Phase 3 pediatric efficacy and safety study; and NCT06415344, a Phase 3 long-term extension study. Total enrollment across these trials is 518 participants.
GTX-102 is not approved; it is an investigational therapy still in clinical development. Ultragenyx Pharmaceutical Inc. is conducting Phase 3 trials in Angelman Syndrome, and the FDA has granted GTX-102 Breakthrough Therapy designation, which is intended to expedite development and review of drugs for serious conditions where preliminary clinical evidence suggests substantial improvement over available therapies.