E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Body processes [G] - Bones and nerves physological processes [G11] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000452 |
E.1.2 | Term | Achondroplasia |
E.1.2 | System Organ Class | 100000004850 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
- 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. |
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E.2.2 | Secondary objectives of the trial |
• 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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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.
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E.4 | Principal 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.
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E.5 End points |
E.5.1 | 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.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
D1, 91, 181, 271, 361, 451, 541, 631, 721 |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Open Label Extension study |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Belgium |
Denmark |
Italy |
Japan |
Portugal |
Spain |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 27 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 27 |