BARZOLVOLIMAB for Chronic Spontaneous Urticaria

Inclusion criteria

• {"criterion_text":"- Able to read, understand, and provide written informed consent themselves, and if applicable, Health Insurance Portability and Accountability Act (HIPAA) authorization, after the nature of the study has been fully explained, and must be willing to comply with all study requirements and procedures"}
• {"criterion_text":"- Must have completed 52 weeks of treatment and the 16-week follow-up in one of the CDX0159-12 or CDX0159-13 clinical studies"}
• {"criterion_text":"- In the opinion of the Investigator, is eligible to participate in the LTE based on a favorable benefit-risk assessment. For participants receiving barzolvolimab retreatment, participants remain eligible to continue treatment in the LTE by not meeting any of the criteria during CDX0159-12 or CDX0159-13 that would have warranted study drug discontinuation."}
• {"criterion_text":"- Female participants receiving barzolvolimab retreatment at study entry must meet 1 of the following criteria: • If of childbearing potential, agrees to use highly effective contraception from the time of Visit 1 and for 150 days after the receipt of study treatment. Highly effective methods of contraception include the following: − combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation, administered as oral, intravaginal, or transdermal − progestogen-only hormonal contraception associated with inhibition of ovulation administered as oral, injectable, or by implantable means − intrauterine device (IUD) − intrauterine hormone-releasing system (IUS) − a vasectomized male partner (male sterilization ≥ 6 months prior to Visit 1 with a medical assessment of the surgical success) as the sole partner for the participant Total abstinence is acceptable when this is in line with the preferred and usual lifestyle of the participant. Periodic abstinence (eg, calendar, ovulation, symptothermal postovulation methods) and withdrawal are not acceptable methods of contraception. The decision on the contraceptive method should be reviewed every 2 months to evaluate the individual need and compatibility of the method chosen if the participant will receive barzolvolimab or receives barzolvolimab at any time during the study. • Females of non-childbearing potential, who are surgically sterile (ie, had undergone complete hysterectomy, bilateral salpingectomy or bilateral oophorectomy, or bilateral tubal ligation) or in a menopausal state (≥ 1 year without menses), or confirmed by follicle-stimulating hormone (FSH) levels, are eligible."}
• {"criterion_text":"- Male participants receiving barzolvolimab retreatment at study entry and with female partners of childbearing potential must agree to use barrier contraceptive methods or have undergone a vasectomy and agree not to donate sperm during the study and for at least 150 days after receipt of study treatment. Additionally, male participants with female partners of childbearing potential must agree to discuss with their partner the use of highly effective contraception methods during the same period of time. When a male participant has undergone a vasectomy, the participant’s medical history should show that the vasectomized participant has documented medical assessment confirming the surgical success of the vasectomy."}
• {"criterion_text":"- Willing and able to comply with all study requirements and procedures, including the completion of a daily symptom Diary during the final month of the CDX0159-12 or CDX0159-13 and throughout the LTE study."}

Exclusion criteria

• {"criterion_text":"- 1. Any other active pruritic skin diseases that would confound CSU assessments (eg, atopic dermatitis, psoriasis, bullous pemphigoid, dermatitis herpetiformis, prurigo nodularis, chronic pruritus of unknown origin) based on the Investigator’s clinical judgment."}
• {"criterion_text":"- 11. History of malignancy within 5 years before enrollment review, except fully treated carcinoma in-situ of the cervix, fully treated and resolved non-metastatic squamous or basal cell carcinoma of the skin"}
• {"criterion_text":"- 13. Procedures requiring general or epidural anesthesia within 8 weeks prior to study treatment, minor procedures (eg, dental) within 14 days prior to study treatment, or anticipation of procedures requiring general anesthesia during study participation."}
• {"criterion_text":"- 14. Prior receipt of any investigational product or other anti-KIT therapy (other than barzolvolimab)."}
• {"criterion_text":"- 15. Inadequate compliance with the Diary during CDX0159-12 or CDX0159-13 sufficient to lead to unacceptable safety risk to study participation, according to the Investigator."}
• {"criterion_text":"- 16. Participants who live in detention on court order or on regulatory action will not be enrolled."}
• {"criterion_text":"- 17. Sponsor or contract research organization (CRO) staff directly involved in the conduct of the study, site staff supervised by the Investigator, and their respective family members."}
• {"criterion_text":"- 18. Participants without at least one documented UAS7 score from Weeks 64-68 of the CDX0159-12 or CDX0159-13 trials."}
• {"criterion_text":"- 12. Any other acute or chronic medical or psychiatric condition or laboratory abnormality that could increase the risk associated with study participation or could interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into the study."}
• {"criterion_text":"- 2. Prohibited non-biologic systemic agents, including investigational agents, within 30 days or 5 half-lives, whichever is longer, prior to enrollment."}
• {"criterion_text":"- 3. Immunomodulating biologic therapy within 3 months prior to enrollment"}
• {"criterion_text":"- 5. Participants in Group 2 (Barzolvolimab Retreatment Group): Women who are pregnant or nursing. All female participants with reproductive potential must have a negative pregnancy test prior to starting barzolvolimab study treatment."}
• {"criterion_text":"- 6. Severe or uncontrolled chronic diseases (eg, chronic hepatic or renal disease, diabetes mellitus) that might interfere with the evaluation of the clinical effect or safety of study treatment or may confound assessment of safety during the trial"}
• {"criterion_text":"- 7. Participants with moderate-to-severe pulmonary or cardiovascular diseases."}
• {"criterion_text":"- 9. Known active hepatitis B, hepatitis C, or HIV infection."}
• {"criterion_text":"- 10. Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antifungals, antiparasitics, or antiprotozoals during the enrollment review. The enrollment review may be extended by 2 weeks to allow for recovery of acute infections independent of requirement for anti-infective treatment"}

Primary endpoints

• {"endpoint_text":"- Time to disease worsening or treatment failure through Week 52 based on the first of the following events: 1. Urticaria Activity Score over 7 days (UAS7) ≥ 16*","definition_or_measurement_approach":"Measured as time-to-event through Week 52; event defined as first occurrence of UAS7 ≥ 16 (Urticaria Activity Score over 7 days)"}
• {"endpoint_text":"- 2. Discontinuation of barzolvolimab in Group 2 (Barzolvolimab Retreatment Group) due to lack of efficacy or to a treatment related adverse event (AE)","definition_or_measurement_approach":"Recorded discontinuation of study drug in Group 2 attributed to lack of efficacy or treatment-related adverse event"}
• {"endpoint_text":"- 3. First use of strongly confounding prohibited medication (Group 1 or 2) or use of barzolvolimab in Group 1","definition_or_measurement_approach":"Time to first use of a prohibited confounding medication or initiation of barzolvolimab in an observation-arm participant"}

Secondary endpoints

• {"endpoint_text":"- 1. In participants in Group 1 (Observation Group): Change from baseline (CDX0159-12 or CDX0159-13) in UAS7 at Week 26; at EOS","definition_or_measurement_approach":"Change from prior study baseline UAS7 score measured at Week 26 and end of study (EOS)"}
• {"endpoint_text":"- 2. In participants in Group 1 (Observation Group) with at least well-controlled disease (UAS7 ≤ 6) at baseline of Long-term Extension (LTE): Percentage of participants with at least well-controlled disease at Week 26; at EOS","definition_or_measurement_approach":"Proportion of participants with UAS7 ≤ 6 at specified timepoints"}
• {"endpoint_text":"- 3. In participants in Group 1 (Observation Group) with complete control (UAS7 = 0) at baseline of LTE: Percentage of participants with at least well-controlled disease at Week 26; at EOS","definition_or_measurement_approach":"Proportion of participants (baseline UAS7=0) who have UAS7 ≤6 at Week 26 and EOS"}
• {"endpoint_text":"- 4. In participants in Group 1 (Observation Group) with chronic spontaneous urticaria (CSU) completely controlled (UAS7 = 0 and Angioedema Activity Score over 7 days [AAS7] = 0) at baseline of LTE: Percentage of participants with CSU completely controlled at Week 26; at EOS","definition_or_measurement_approach":"Proportion maintaining UAS7 = 0 and AAS7 = 0 at Week 26 and EOS"}
• {"endpoint_text":"- 5. In participants in Group 1 (Observation Group) with at least well-controlled disease (UAS7 ≤ 6) at baseline of LTE: Time to loss of well-controlled disease through EOS","definition_or_measurement_approach":"Time to first occurrence of UAS7 > 6 through EOS"}
• {"endpoint_text":"- 6. In participants in Group 1 (Observation Group) with complete control of disease (UAS7 = 0) at baseline of LTE: Time to loss of complete control through EOS","definition_or_measurement_approach":"Time to first occurrence of UAS7 > 0 through EOS"}
• {"endpoint_text":"- 7. In participants in Group 1 (Observation Group) with CSU completely controlled (UAS7 = 0 and AAS7 = 0) at baseline of LTE: Time to loss of CSU completely controlled through EOS","definition_or_measurement_approach":"Time to loss of combined UAS7=0 and AAS7=0 through EOS"}
• {"endpoint_text":"- 8i. In participants in Group 2 (Barzolvolimab Retreatment Group): • Change from LTE baseline UAS7 at Week 12; at Week 24; at Week 52; at EOS","definition_or_measurement_approach":"Change in UAS7 from LTE baseline at Weeks 12, 24, 52 and EOS"}
• {"endpoint_text":"- 8ii. Percentage of participants with UAS7 ≤ 6 at Week 12; at Week 24; at Week 52; at EOS","definition_or_measurement_approach":"Proportion of participants achieving UAS7 ≤ 6 at specified timepoints"}
• {"endpoint_text":"- 9i. In participants in Group 1 (Observation Group): Percentage of participants experiencing AEs from baseline through EOS","definition_or_measurement_approach":"Proportion of participants reporting any adverse events from baseline to EOS"}
• {"endpoint_text":"- 9ii. In participants in Group 1 (Observation Group): Percentage of participants experiencing serious AEs from baseline through EOS","definition_or_measurement_approach":"Proportion reporting serious adverse events (SAEs) from baseline to EOS"}
• {"endpoint_text":"- 9iii. In participants in Group 1 (Observation Group) who never receive barzolvolimab retreatment during the LTE: Percentage of participants experiencing non-treatment emergent AEs from baseline through EOS","definition_or_measurement_approach":"Proportion with non-treatment-emergent AEs from baseline to EOS"}
• {"endpoint_text":"- 10i. In participants in Group 1 (Observation Group) who never receive barzolvolimab retreatment during the LTE: Percentage of participants experiencing non-treatment emergent serious AEs from baseline through EOS","definition_or_measurement_approach":"Proportion with non-treatment-emergent SAEs from baseline to EOS"}
• {"endpoint_text":"- 10ii. In participants in Group 1 (Observation Group) who receive barzolvolimab retreatment during the LTE: Percentage of participants experiencing treatment emergent adverse events (TEAEs) from baseline through EOS","definition_or_measurement_approach":"Proportion with TEAEs from baseline to EOS"}
• {"endpoint_text":"- 11i. In participants in Group 1 (Observation Group) who receive barzolvolimab retreatment during the LTE: Percentage of participants experiencing treatment emergent serious AEs from baseline through EOS","definition_or_measurement_approach":"Proportion with treatment-emergent SAEs from baseline to EOS"}
• {"endpoint_text":"- 11ii. In participants in Group 1 (Observation Group) who receive barzolvolimab retreatment during the LTE: Percentage of participants experiencing TEAEs leading to treatment discontinuation from baseline through EOS","definition_or_measurement_approach":"Proportion with TEAEs that lead to treatment discontinuation"}
• {"endpoint_text":"- 12. In participants in Group 2 (Barzolvolimab Retreatment Group): • Percentage of participants experiencing TEAEs from baseline through EOS • Percentage of participants experiencing treatment-emergent serious AEs from baseline through EOS • Percentage of participants experiencing TEAEs leading to treatment discontinuation from baseline through EOS","definition_or_measurement_approach":"Safety endpoints measured as proportions of participants experiencing TEAEs, serious TEAEs, and TEAEs causing discontinuation from baseline to EOS"}

Primary sponsor

Full Name

Celldex Therapeutics Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

PPD Development LP

Responsibilities

sponsorDuties codes: 1,12,5; also listed in multiple locations (clinical operations / lab functions)

Name

PPD Global Ltd.

Responsibilities

ADA/PK and related lab responsibilities (codes indicated in record)

Third parties

• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"sponsorDuties codes: 1,12,5","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Catalent Germany Schorndorf GmbH","duties_or_roles":"sponsorDuties codes: 14","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Canfield Scientific Inc.","duties_or_roles":"Photo collection services","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"biopsy storage and shipment; code 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"eCOA; code 3","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Intuvigilance Limited","duties_or_roles":"sponsorDuties code: 8","organisation_type":"Industry"}
• {"country":"United States","full_name":"PPD Development LP (Richmond address)","duties_or_roles":"ADA/PK; code 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Patient concierge","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Croatia","full_name":"Optimapharm d.o.o.","duties_or_roles":"sponsorDuties code: 12","organisation_type":"Pharmaceutical company"}
• {"country":"Greece","full_name":"PPD Global Ltd.","duties_or_roles":"sponsorDuties codes: 12,5","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties code: 7","organisation_type":"Non-Pharmaceutical company"}