Interventional Study of Infigratinib in Children < 3 Years Old With Achondroplasia (ACH)

QED Therapeutics, Inc., a Bridgebio company

Status and phase: Begins enrollment this month; Phase 2

Conditions: Achondroplasia

Treatments: Drug: Infigratinib or placebo comparator is provided as sprinkle capsules for daily oral administration; Drug: Infigratinib is provided as sprinkle capsules for daily oral administration; Drug: Infigratinib is provided as a single dose of minitablets for oral administration

Study type: Interventional

Funder types: Industry

Identifiers

NCT07169279

QBGJ398-204

Details and patient eligibility

About

This is a Phase 2, multicenter, randomized, placebo-controlled study to evaluate the safety and efficacy of infigratinib in participants < 3 years old with ACH. The purposes of the SAD and Phase 2 portions are to identify and confirm the dose of infigratinib to be used in the Phase 2b portion, based on safety and PK. The purpose of the Phase 2b, placebo-controlled portion is to evaluate the safety and efficacy of infigratinib in children < 3 years old with ACH at the selected dose.

Full description

PROPEL Infant & Toddler (I&T) is a Phase 2, multicenter, randomized, placebo-controlled study that comprises 4 portions: the single ascending dose (SAD) portion (open-label), the Phase 2 portion (open-label), the Phase 2b portion (placebo-controlled), and an Extension Portion (open-label). The study will evaluate children with ACH < 3 years old being administered oral infigratinib.

Enrollment: 77 estimated patients

Sex: All

Ages: Under 32 months old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of ACH confirmed by genetic testing. If prospective participants had prior genetic testing, the diagnosis must be confirmed by a report from a certified laboratory, documenting the specific mutation.
• Age 0 to 32 months (2 years and 8 months) at screening.
• Signed informed consent, which must be obtained from each participant's parent(s) or legal guardian.
• Parent(s)/Guardian(s) willing and able to attend all study visits and comply with all study requirements.
• Parent(s)/Guardian(s) willing and able to comply with the routine care of the study participants according to local guidance for the management of infants and young children with ACH.
• Able to swallow age-appropriate oral medication.
• In participants <1 year old, be compliant with recommended vitamin D supplementation of 5 10 μg/day or higher (or as recommended by country specific guidelines).

Exclusion criteria

• Participants who have hypochondroplasia or diagnosis of genetic condition other than ACH, or any clinical condition that can affect growth.
• Gestational age at birth <37 weeks and/or birth weight <2500 grams.
• Gastroesophageal reflux disease requiring prolonged treatment (>1 week) with prohibited medications.
• Evidence of cervicomedullary compression, as defined by an Achondroplasia Foramen Magnum Score (AFMS) 4, symptomatic or asymptomatic, diagnosed during MRI done at screening or a previous MRI done at any time if the participant had not undergone decompression surgery.
• History of fracture of a long bone or spine within 6 months prior to screening.
• Any other significant concurrent disease or condition that, in the view of the investigator and/or sponsor, would confound assessment of efficacy or safety of infigratinib and/or would require treatment with a prohibited medication (per protocol), and/or would place the participant at high risk for poor treatment compliance or for failure to complete the study.
• Regular long-term (>3 weeks; more than twice/year) treatment with supraphysiologic doses of glucocorticoid therapy (ie, >15 mg/m2/day of hydrocortisone or equivalent) or treatment with glucocorticoids at anti-inflammatory doses (for over 3 weeks within 6 months of the screening visit. NOTE: Low-dose topical, inhaled, or intranasal corticosteroids are acceptable.
• Significant abnormality in screening laboratory results,
• Allergy or hypersensitivity to any components of the study drug.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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77 participants in 15 patient groups, including a placebo group

SAD Cohort 1 infigratinib (2 to less than 3 years old)

Experimental group

Description:

Single Ascending Dose Escalation and PK Portion

Treatment:

Drug: Infigratinib is provided as a single dose of minitablets for oral administration

SAD Cohort 2 infigratinib (1 to less than 2 years old)

Experimental group

Description:

Single Ascending Dose Escalation and PK Portion

Treatment:

Drug: Infigratinib is provided as a single dose of minitablets for oral administration

SAD Cohort 3 infigratinib (6 months to less than 1 year old)

Experimental group

Description:

Single Ascending Dose Escalation and PK Portion

Treatment:

Drug: Infigratinib is provided as a single dose of minitablets for oral administration

SAD Cohort 4 infigratinib (0 to less than 6 months old)

Experimental group

Description:

Single Ascending Dose Escalation and PK Portion

Treatment:

Drug: Infigratinib is provided as a single dose of minitablets for oral administration

Phase 2 Cohort 1 infigratinib (2 to less than 3 years old)

Experimental group

Description:

Open-label Safety and PK Portion

Treatment:

Drug: Infigratinib is provided as sprinkle capsules for daily oral administration

Drug: Infigratinib is provided as sprinkle capsules for daily oral administration

Phase 2 Cohort 2 infigratinib (1 to less than 2 years old)

Experimental group

Description:

Open-label Safety and PK Portion

Treatment:

Drug: Infigratinib is provided as sprinkle capsules for daily oral administration

Drug: Infigratinib is provided as sprinkle capsules for daily oral administration

Phase 2 Cohort 3 infigratinib (6 months to less than 1 year old)

Experimental group

Description:

Open-label Safety and PK Portion

Treatment:

Drug: Infigratinib is provided as sprinkle capsules for daily oral administration

Drug: Infigratinib is provided as sprinkle capsules for daily oral administration

Phase 2 Cohort 4 infigratinib (0 to less than 6 months)

Experimental group

Description:

Open-label Safety and PK Portion

Treatment:

Drug: Infigratinib is provided as sprinkle capsules for daily oral administration

Drug: Infigratinib is provided as sprinkle capsules for daily oral administration

Phase 2B Cohort 1 infigratinib (2 to less than 3 years old)

Experimental group

Description:

Randomized Safety and Efficacy Portion

Treatment:

Drug: Infigratinib or placebo comparator is provided as sprinkle capsules for daily oral administration

Phase 2B Cohort 2 infigratinib (6 months to less than 2 years old)

Experimental group

Description:

Randomized Safety and Efficacy Portion

Treatment:

Drug: Infigratinib or placebo comparator is provided as sprinkle capsules for daily oral administration

Phase 2B Cohort 3 infigratinib (0 to less than 6 months old)

Experimental group

Description:

Randomized Safety and Efficacy Portion

Treatment:

Drug: Infigratinib or placebo comparator is provided as sprinkle capsules for daily oral administration

Open- label Extension infigratinib (0 months to 3 years [+6 months old])

Experimental group

Description:

Open-label extension portion continuing to assess safety and efficacy in children until they reach 3 years old (+6 months)

Treatment:

Drug: Infigratinib is provided as sprinkle capsules for daily oral administration

Drug: Infigratinib is provided as sprinkle capsules for daily oral administration

Phase 2B Cohort 1 Placebo (2 to less than 3 years old)

Placebo Comparator group

Description:

Randomized Safety and Efficacy study

Treatment:

Drug: Infigratinib or placebo comparator is provided as sprinkle capsules for daily oral administration

Phase 2B Cohort 2 placebo (6 months to less than 2 years old)

Placebo Comparator group

Description:

Randomized Safety and Efficacy study

Treatment:

Drug: Infigratinib or placebo comparator is provided as sprinkle capsules for daily oral administration

Phase 2B Cohort 3 Placebo (0 to less than 6 months old)

Placebo Comparator group

Description:

Randomized Safety and Efficacy study

Treatment:

Drug: Infigratinib or placebo comparator is provided as sprinkle capsules for daily oral administration