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

• Register: EUCTR
• Last refreshed on: 30 August 2021
• Main ID: EUCTR2020-001189-13-IT
• Date of registration: 15/06/2021
• Prospective Registration: No
• Primary sponsor: PFIZER INC
• Public title: Phase 2 study of safety, tolerability, PK and efficacy of recifercept in achondroplasia
• Scientific title: A PHASE 2 MULTIPLE DOSE, RANDOMIZED STUDY TO ASSESS THE SAFETY, TOLERABILITY, PHARMACOKINETICS AND EFFICACY OF RECIFERCEPT IN CHILDREN WITH ACHONDROPLASIA - -
• Date of first enrolment: 05/02/2021
• Target sample size: 63
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-001189-13
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: yes Double blind: no Parallel group: yes Cross over: no Other: yes Other trial design description: Same product, different dose If controlled, specify comparator, Other Medicinial Product: yes 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 Kingdom, 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.Main cohort: Aged >= 2 years to <11 years (up to the day before 11th birthday inclusive) at time of enrollment; or exploratory cohort: aged >=3 months to <2years (up to the day before 2nd birthday inclusive) at time of enrollment.
Type of Participant and Disease Characteristics
2. Documented, confirmed genetic diagnosis of achondroplasia from historical medical records prior to entry into this trial (test must have been performed at a laboratory fully accredited for genetic testing under
local regulations).
3. Completed the C4181001 natural history study with at least 2 valid height/length measurements (at least 3 months apart) prior to enrollment in this study. One of these measurement timepoints must be within the 3 months prior to enrollment in C4181005.
4. Tanner stage 1 based on investigator assessment during physical examination (must include assessment of breast development for females, testicular stage for males).
5. Able to stand independently for height measurements (if >2 years of age at enrollment).
6. If aged <2 years at enrollment, has a documented historical MRI brain/cervical spine performed in the previous 12 months.
7. 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.
8. Following receipt of oral and written information about the trial, the child (depending on local institutional review board/independent ethics committee requirements) must provide assent, and one or both
(according to local regulations) parents or 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:
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:
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)
4. Known closure of long bone growth plates (cessation of height growth).
5. Body weight <7 kg or >30 kg.
6. Severe renal impairment (eGFR <60 ml/min/1,73m2) or hepatic impairment (AST/ALT >1,5 ULN).
7. History of hypersensitivity to study intervention or any excipients.
8. History of any prior treatment with human growth hormone or related products (including insulin-like growth factor 1 [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 mcg/day beclametasone 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.
15. History of receipt of any investigational product for achondroplasia or that may affect growth/interpretation of growth parameters.
16. History of receipt of an investigational product (not for achondroplasia/growth affecting) within the last 30 days or 5 half-lives (whichever is longer).
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

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

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

Intervention(s)

Product Name: Recifercept
Product Code: [PF-07256472]
Pharmaceutical Form: Lyophilisate for solution for injection
INN or Proposed INN: Recifercept
Current Sponsor code: PF-07256472
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Primary Outcome(s)

Secondary Objective: - To evaluate the pharmacokinetics (PK) of recifercept in children aged >2 to <11 years old with achondroplasia.
- To assess efficacy of recifercept to improve achodroplasia-related complications
- Assess change in individual safety parameters

Main Objective: - Evaluate the safety and tolerability of recifercept doses and dosing regimes in participants aged >2 to <11 years with achondroplasia.
- To assess efficacy of recifercept to increase height growth in children with achondroplasia.

Primary end point(s): - Safety and tolerability of recifercept as assessed through frequency and severity of AEs/SAEs.
- Increase in height growth above expected in reference population [Merker et al,2018]

Timepoint(s) of evaluation of this end point: At screening, D1, D4, D8, D15, D29, D61, D91, D121, D152, D183, D274, D2, D365

Secondary Outcome(s)

Secondary end point(s): - Population PK characterization in children aged >2 to <11 years old with achondroplasia. Clearance (CL/F) and other PK parameters of recifercept to assess exposures in different age group.
- Sitting height/standing height ratio.
- Arm span to height/length difference.
- Knee height:lower segment ratio.
- Occipito-frontal circumference.
- Ratio of occipito-frontal distance to occipito-mid-face measurements.
- z-score of the above proportionality and skull morphology where achondroplasia reference datasets exist (occipito-frontal circumference, arm span, sitting height).
- Fixed flexion angles at elbow.
- Polysomnography parameters in those with pre-existing sleepdisordered breathing at the time of enrollment.
- Body mass index (BMI).
- Waist:chest circumference ratio.
- Change from baseline in CHAQ component and index scores, QoLISSY Brief total score.
- Change from baseline in safety labs, vital signs, physical examination.
- Rate of anti-drug antibodies.

Timepoint(s) of evaluation of this end point: At screening, D1, D4, D8, D15, D29, D61, D91, D121, D152, D183, D274, D2, D365

Secondary ID(s)

2020-001189-13-PT

C4181005

Source(s) of Monetary Support

Pfizer Inc.

Ethics review

Status: Approved
Approval date: 19/11/2020
Contact: