A Phase 2b, Multicenter, Double-blind, Randomized, Placebo Controlled Study to Assess the Efficacy and Safety of Weekly Doses of GLM101 Administered Intravenously to Participants With PMM2-CDG (POLAR Trial)
This study is evaluating the safety, effectiveness, and how the body absorbs, distributes, and eliminates GLM101, for participants with PMM2-CDG, including children, adolescents, and adults. Researchers will compare participants receiving GLM101 to those receiving a placebo to see if GLM101 improves symptoms of PMM2-CDG. The study includes two treatment parts: a 24-week double blind placebo-controlled treatment period (Part A), and a 24-week open-label phase where every participant will receive GLM101(Part B).
• Participant is aged ≥ 4 years old at the time of signing the consent.
• Participant with molecular diagnosis of PMM2-CDG. Diagnosis is defined as biallelic pathogenic and/or likely pathogenic variants, or, in the case of variants of uncertain pathogenicity, demonstration of biallelic variants and PMM2 enzyme activity consistent with a diagnosis of PMM2-CDG. Diagnosis with laboratory report(s) on file is required.
• Participant is willing and capable of completing the ICARS in its entirety without any assessment deemed as not evaluable.
• Participant screening total ICARS score is ≥ 20 and ≤ 80 .
• Male or female participant has appropriate measures in place to prevent pregnancy:
‣ If the participant is a woman of childbearing potential, i.e., fertile, following menarche and until becoming postmenopausal unless permanently sterile (permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy), she must not be pregnant (confirmed by a negative serum pregnancy test), is using a medically accepted method of contraception (abstinence, a hormonal contraceptive associated with inhibition of ovulation in conjunction with a barrier method, or use of an intrauterine device), and must agree to continue using this method for 50 days after the last infusion. Note: sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the participant. Periodic abstinence (calendar, symptothermal, post-ovulation methods) is not an acceptable method of contraception.
⁃ If the participant is a female of non-childbearing potential, she must be premenarchal, surgically sterile, or must have an ovarian dysfunction confirmed by a follicle stimulating hormone \> 40 IU/ L (or higher per local institutional guidelines) and absence of menses for 12 months after last menstrual bleeding without an alternative medical cause.
⁃ If the participant is a sexually active male with female partners, the participant agrees to use a medically acceptable method of contraception (abstinence, the partner taking a hormonal contraceptive in conjunction with male participant using male condom, or use by the partner of an intrauterine device with a male participant using male condom) and agrees to continue using this method for 50 days after the last infusion.
• If the participant is male, he must agree to refrain from donating sperm during the study and 50 days after the last infusion.
• The participant is willing and able to provide informed consent/assent, directly or through his/her legally authorized representative.
• The participant has a caregiver who is willing and able to complete questionnaires and provide informed consent.