Clinical Trials

Date: 2018-01-08

Type of information: Interim results

phase: 2

Announcement: interim results

Company: Acceleron Pharma (USA - CA)

Product: ACE 083

Action mechanism:

• protein. ACE-083 is a therapeutic candidate based on the naturally-occurring protein follistatin. It acts as a ligand trap for members in the transforming growth factor-beta (TGF-Beta) superfamily involved in the regulation of muscle mass and strength. ACE-083 has been designed to increase muscle mass and strength selectively in the muscles into which the drug is administered. Acceleron is developing ACE-083 for diseases such as facioscapulohumeral muscular dystrophy, a rare genetic muscle disorder that results in progressive focal muscle loss and weakness. Improved muscle strength in a specific set of muscles may provide a clinical benefit in this disease.

Disease: facioscapulohumeral muscular dystrophy (FSHD)

Therapeutic area: Rare diseases - Genetic diseases - Neuromuscular diseases

Country: USA

Trial details:

• Study A083-02 is a multicenter, Phase 2 study to evaluate the safety, tolerability, pharmacodynamics (PD), efficacy, and pharmacokinetics (PK) of ACE 083 in patients with FSHD to be conducted in two parts. Part 1 is open-label, dose-escalation and Part 2 is randomized, double-blind, and placebo-controlled. (NCT02927080)

Latest news:

• • On January 8, 2018, Acceleron Pharma announced positive preliminary results for the first two cohorts in Part 1 of the Phase 2 clinical trial with ACE-083 in patients with facioscapulohumeral dystrophy (FSHD). Part 1 of the Phase 2 trial is an open-label, dose-escalation study of ACE-083 designed to evaluate safety as well as changes in total muscle volume in up to 36 patients with FSHD. Preliminary results include data from 23 patients evaluable for magnetic resonance imaging (MRI) among two different cohorts (11 patients with tibialis anterior weakness and 12 patients with biceps brachii weakness). Each patient received ACE-083 (150 mg or 200 mg) as a unilateral intramuscular injection once every three weeks for 12 weeks. Total muscle volume changes were measured by MRI relative to baseline at 3 weeks after the last injection of ACE-083. Based on overlap in dosing on a milligram per gram muscle analysis, dose cohorts were pooled for the analyses of each muscle.
• Tibialis Anterior Part 1 Cohorts (150 mg and 200 mg pooled) Preliminary Results (n=11): The tibialis anterior (TA), which is located in the lower leg, is the main muscle responsible for ankle dorsiflexion, or the ability to lift the front of the foot when taking a step. Over 70% of FSHD patients experience tibialis anterior weakness over the course of their disease, which can lead to general decreased mobility and an increased frequency of falling.
• The TA cohorts generated a mean total muscle volume increase of 12.6%. The TA cohorts produced a mean decrease or improvement in muscle fat fraction of 5.3%
• Biceps Brachii Part 1 Cohorts (150 mg and 200 mg pooled) Preliminary Results (n=12): The biceps brachii (BB), which is located in the upper arm, is a major muscle responsible for elbow flexion, or the ability to lift the lower arm. A majority of FSHD patients experience biceps brachii weakness early in their disease, which leads to the inability to lift objects or perform other important daily activities without assistance.
• The BB cohorts generated a mean total muscle volume increase of 13.2%.
• The BB cohorts produced a mean decrease or improvement in muscle fat fraction of 0.6%.
• In the BB cohorts, the majority of patients had less intramuscular fat at baseline relative to the patients in the TA cohorts. Patients with higher fat fraction in the BB cohorts at baseline demonstrated larger decreases in fat fraction with treatment.
• Strength and Function Tests: Strength and function tests are being explored in Part 1 to assist with the design of the randomized, double-blind, placebo-controlled Part 2 of the study. Given the lack of placebo control and small sample size of patients in Part 1, no conclusions can be made on the strength and function assessments at this time. Effects of ACE-083 on strength and function versus a placebo-control will be evaluated in Part 2 of the study.Part 1 Preliminary Safety Results (n=25): There were no serious adverse events reported. The most common adverse events were injection site related and grades 1-2. One patient experienced a related grade 3 non-serious adverse event of lower leg intramuscular swelling. This patient fully recovered and was discontinued from the study.
• Acceleron plans to present an in-depth review of Part 1 data at a medical conference in 2018. The company also plans to initiate Part 2 of the ACE-083 FSHD Phase 2 trial during the second quarter of 2018. 
• • On December 22, 2016, Acceleron Pharma announced that the first patient has been treated in a Phase 2 clinical trial of ACE-083, the Company’s locally acting muscle agent, for the treatment of patients with facioscapulohumeral muscular dystrophy (FSHD). The two-part Phase 2 clinical trial is designed to evaluate ACE-083 in FSHD patients with muscle weakness in either the tibialis anterior, a muscle in the lower leg involved in foot flexion, or the biceps. Part 1 is an open-label, dose-escalation study of ACE-083 administered by intramuscular injection once every three weeks in up to 36 patients to evaluate safety and increases in muscle volume over a three-month treatment period. Part 2 is a randomized, double-blind, placebo-controlled study using the optimal dose level selected in Part 1. Up to 40 patients will be randomized to receive either placebo or ACE-083 administered by intramuscular injection once every three weeks and evaluated for increases in muscle volume, strength, function and safety over a three-month treatment period.

 

Is general: Yes