An Extension Study of AG-348 in Adult Subjects with Pyruvate Kinase Deficiency Previously Enrolled in AG-348 Studies

Phase 1

• Conditions: Pyruvate Kinase Deficiency Haemolytic anaemia; MedDRA version: 21.1Level: PTClassification code 10037682Term: Pyruvate kinase deficiency anaemiaSystem Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2018-003459-39-IT
• Lead Sponsor: AGIOS PHARMACEUTICALS, INC.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-01-05
• Last Update Posted: 11 January 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 116

Inclusion Criteria

1.Have signed written informed consent prior to participating in this extension study;
2.Have completed either antecedent study AG348-C-006 or AG348-C-007 through the Part 2 Week 24 Visit;
3.Cohorts 2 and 3: Have demonstrated clinical benefit from AG-348 treatment in the antecedent study, in the opinion of the Investigator;
4.For women of reproductive potential, have a negative pregnancy test at the Screening/Day 1 Visit;
5.For women of reproductive potential as well as men with partners who are women of reproductive potential, be abstinent as part of their usual lifestyle, or agree to use 2 forms of contraception, 1 of which must be considered highly effective, from the time of giving informed consent, during the study, and for 28 days (both men and women) following the last dose of study drug.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 116
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Have a significant medical condition (including clinically significant laboratory abnormality) that developed during his/her antecedent AG-348 study that confers an unacceptable risk to participating in this extension study, that could confound the interpretation of the study data, and/or that compromises the ability of the subject to complete study visits and procedures;
2.Are currently pregnant or breastfeeding;
3.Have a splenectomy scheduled during the study treatment period;
4.Meet the withdrawal criteria of his/her antecedent AG-348 study during screening of this extension study. Withdrawal criteria of the antecedent AG-348 studies are as follows:
- Withdrawal of consent
- Development of an intercurrent medical condition that precludes further participation in the study
- Subject requires use of a prohibited concomitant medication
- Investigator decision
- Persistent nonadherence to protocol requirements
- Pregnancy
- Lost to follow-up
5.Are currently receiving medications that are strong inhibitors of cytochrome P450 (CYP)3A4, strong inducers of CYP3A4, strong inhibitors of P-glycoprotein (P-gp), or digoxin (a P-gp sensitive substrate medication) that have not been stopped for a duration of at least 5 days or a timeframe equivalent to 5 half-lives (whichever is longer) prior to start of study drug on this extension study;
6.Have received anabolic steroids, including testosterone preparations, within 28 days prior to Screening/Day 1 of this extension study;
7.Have received hematopoietic stimulating agents (eg, erythropoietins, granulocyte colony stimulating factors, thrombopoietins) within 28 days start of study drug on this extension study;
8.Have exposure to any investigational drug other than AG-348, device, or procedure within 3 months prior to Screening/Day 1 of this extension study.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the long-term safety and tolerability of AG-348;Secondary Objective: •To evaluate the long-term efficacy of AG-348<br>•To evaluate the efficacy of AG-348 in increasing hemoglobin (Hb) concentrations in subjects who previously received placebo in Study AG348-C-006 (ie, Cohort 1)<br>•To determine the effect of AG-348 on health-related quality of life (HRQoL) using patient reported outcomes (PROs)<br>•To evaluate the pharmacokinetics of AG-348 after oral administration (Cohort 1 only)<br>•To evaluate the relationship between AG-348 pharmacokinetics and safety parameters (Cohort 1 only);Primary end point(s): 1)Number of Subjects with Adverse Events (AEs) and Adverse Events of Special Interest (AESIs)<br>2)Number of Subjects with AEs Leading to Dose Reduction, Treatment Interruption and Treatment Discontinuation;Timepoint(s) of evaluation of this end point: From baseline to end of study (Week 197)