Phase 2 study of long-term safety, tolerability, PK and efficacy of recifercept in achondroplasia

• Register: EUCTR
• Last refreshed on: 26 September 2023
• Main ID: EUCTR2021-003149-39-ES
• Date of registration: 17/09/2021
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc.
• Public title: Phase 2 study of long-term safety, tolerability, PK and efficacy of recifercept in achondroplasia
• Scientific title: A PHASE 2 OPEN LABEL EXTENSION STUDY TO ASSESS THE LONG-TERM SAFETY, TOLERABILITY, PHARMACOKINETICS AND EFFICACY OF RECIFERCEPT IN CHILDREN WITH ACHONDROPLASIA
• Date of first enrolment: 14/12/2021
• Target sample size: 63
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2021-003149-39
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: yes Other trial design description: Open Label Extension study If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Denmark, Italy, Japan, Portugal, Spain, United States

Contacts

• Name: Clinical Trials.gov Call Centre
• Affiliation: Pfizer Inc.

• Name: Clinical Trials.gov Call Centre
• Affiliation: Pfizer Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
Age and Sex:
1. Male and female participants between the ages of =15 months to =12 years inclusive, at Visit 1 (Screen 1).
• Refer to Appendix 4 for reproductive criteria for male (Section 10.4.1) and female (Section 10.4.2) participants.

Type of Participant and Disease Characteristics:
2. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests lifestyle considerations and other study procedures.
3. Completed the C4181005 Phase 2 study.
4. Able to stand independently for height measurements (if =2 years of age at enrollment).

Informed Consent:
5. Capable of giving signed informed consent/assent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.
6. Following receipt of oral and written information about the trial, the child (depending on local IRB/independent EC requirements) must provide assent, and 1 or both (according to local regulations) parent(s) or legal guardians of the child must provide signed informed consent before any trial-related activity is carried out.
Are the trial subjects under 18? yes
Number of subjects for this age range: 63
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Medical Conditions:
1. Presence of co-morbid conditions or circumstances that, in the opinion of the investigator, would affect interpretation of growth data or ability to complete the trial procedures.
2. Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the participant inappropriate for the study.
3. Presence of severe obesity (BMI >95th percentile on Hoover-Fong BMI charts) [Hoover-Fong et al, 2008].
4. Known closure of long bone growth plates (cessation of height growth).
5. Body weight = 45 kg.
6. History of hypersensitivity to study intervention or any excipients.

Prior/Concomitant Therapy:
7. Current use of any prohibited concomitant medication(s) or those unwilling/unable to use a permitted concomitant medication(s). Refer to Section 6.8 Concomitant Therapy.
8. History of any prior treatment with human growth hormone or related products (including IGF-1).
9. History of receipt of any treatment that are known to potentially affect growth (including oral steroids >5 days in the last 6 months, high dose inhaled corticosteroids (>800 µg/day beclomethasone equivalent) and medication for attention deficit hyperactivity disorder).
10. History of limb lengthening surgery (defined as distraction osteogenesis/Ilizarov/callostasis technique following submetaphyseal osteotomy to extend bone length).
11. Any limb lengthening/corrective orthopaedic surgery planned at any point during the trial period.
12. Less than 6 months since fracture or surgical procedure of any bone determined from the screening visit date.
13. Presence of any internal guided growth plates/devices.
14. History of removal of internal guided growth plates/devices within less than 6 months.

Prior/Concurrent Clinical Study Experience:
15. History of receipt of any other (except recifercept) IP for achondroplasia or that may affect growth/interpretation of growth parameters.
16. Previous administration with an investigational drug (not for achondroplasia/growth affecting) within 30 days (or as determined by the local requirement) or 5 half lives preceding the first dose of study intervention used in this study (whichever is longer).

Other Exclusions:
17. Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Achondroplasia
MedDRA version: 20.0 Level: LLT Classification code 10000452 Term: Achondroplasia System Organ Class: 100000004850

Therapeutic area: Body processes [G] - Bones and nerves physological processes [G11]

Intervention(s)

Product Name: Recifercept (proposed INN)
Product Code: PF-07256472
Pharmaceutical Form: Lyophilisate for solution for injection
INN or Proposed INN: Recifercept (proposed INN)
Current Sponsor code: PF-07256472
Other descriptive name: TA-46
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Primary Outcome(s)

Primary end point(s): •The primary efficacy estimand is intended to provide a population level estimate of the effect of the IP on a continuous endpoint.
•Population-level summary: ratio between participants in the trial and a reference population [Merker et al, 2018] in growth of height at 24 month; ratio between treated and reference population is observed change-from-baseline of treated participants standardized by reference participant given age and gender.

Timepoint(s) of evaluation of this end point: D1, 91, 181, 271, 361, 451, 541, 631, 721

Main Objective: - Evaluate the long-term safety and tolerability of recifercept doses and dosing regimes in participants aged =15m to <12 years with achondroplasia.

- To assess long-term efficacy of recifercept to increase height growth in children with achondroplasia.

Secondary Objective: •To evaluate the PK of recifercept in children aged =15m to <12 years old with achondroplasia.

•To assess efficacy of recifercept to improve achondroplasia-related complications.

•Assess change in individual safety parameters.

Secondary Outcome(s)

Secondary end point(s): N/A

Timepoint(s) of evaluation of this end point: N/A

Secondary ID(s)

C4181008

Source(s) of Monetary Support

Pfizer Inc.

Ethics review

Status: Approved
Approval date: 13/12/2021
Contact: