PMID- 27287439
OWN - NLM
STAT- MEDLINE
DCOM- 20170313
LR  - 20181113
IS  - 1477-7827 (Electronic)
IS  - 1477-7827 (Linking)
VI  - 14
IP  - 1
DP  - 2016 Jun 10
TI  - Safety and efficacy of Ovaleap(R) (recombinant human follicle-stimulating hormone) 
      for up to 3 cycles in infertile women using assisted reproductive technology: a 
      phase 3 open-label follow-up to Main Study.
PG  - 31
LID - 10.1186/s12958-016-0164-y [doi]
LID - 31
AB  - BACKGROUND: Ovaleap(R) (follitropin alfa), a recombinant human follicle-stimulating 
      hormone intended for use in controlled ovarian stimulation in women undergoing 
      assisted reproductive technologies (ART), showed therapeutic equivalence to 
      Gonal-f(R) in a multinational, multicenter, randomized, controlled, assessor-blind 
      phase 3 Main Study. The current study examined safety, including immunogenicity, 
      and efficacy of Ovaleap(R) in an open-label, uncontrolled, follow-up treatment 
      period of up to 2 additional treatment cycles in patients who did not become 
      pregnant in the phase 3 Main Study. METHODS: Patients with negative biochemical 
      or clinical pregnancy in the phase 3 Main Study, regardless of treatment group 
      (ie, Ovaleap(R) or Gonal-f(R)), were eligible to participate. Patients received 
      Ovaleap(R) (Merckle Biotec GmbH, Ulm, Germany) for up to 2 additional cycles, 
      administered using a reusable semi-automated pen device. The primary objective 
      was the assessment of safety, including adverse events (AEs), ovarian 
      hyperstimulation syndrome (OHSS), and anti-drug antibodies. Tolerability, patient 
      satisfaction with the Ovaleap(R) pen device, and efficacy outcomes (as evaluated in 
      the Main Study) were also assessed. RESULTS: One hundred forty-seven patients 
      were included in cycle 2, and 61 patients were included in cycle 3. In cycles 2 
      and 3, 10.9 % (16/147) and 6.6 % (4/61) of patients experienced 
      treatment-emergent AEs (TEAEs), respectively. Three serious TEAEs (ie, 
      appendicitis, OHSS, and borderline ovarian tumor) were reported and successfully 
      resolved. The OHSS TEAE was the only OHSS reported in the study (0.7 % [1/147]). 
      Positive findings on anti-drug antibody assays in 6 serum samples did not show 
      neutralizing activity or clinical relevance in biochemical pregnancy rate. No 
      hypersensitivity reaction occurred. Most patients reported "very good"/"good" 
      local tolerability. All patients were "very confident"/"confident" about dose 
      accuracy and correctness of the injection. They all found use of the pen "very 
      convenient"/"convenient" and were all "very satisfied"/"satisfied" with the pen 
      device. Efficacy outcomes were consistent with the phase 3 Main Study. 
      CONCLUSIONS: These findings further support the safety, including immunogenicity, 
      and efficacy of Ovaleap(R) for stimulation of follicular development in infertile 
      women undergoing ART. The findings support continued use of Ovaleap(R) for multiple 
      cycles or a switch to Ovaleap(R) if pregnancy is initially not achieved with 
      Gonal-f(R). TRIAL REGISTRATION: EudraCT number: 2009-017674-20. Current controlled 
      trials register number: ISRCTN74772901 .
FAU - Strowitzki, Thomas
AU  - Strowitzki T
AD  - Department of Gynecological Endocrinology and Reproductive Medicine, University 
      of Heidelberg, Im Neuenheimer Feld 440, 69120, Heidelberg, Germany. 
      Thomas_Strowitzki@med.uni-heidelberg.de.
FAU - Kuczynski, Waldemar
AU  - Kuczynski W
AD  - Centre for Reproductive Medicine, Cryobank, Poland.
AD  - Department of Gynaecology and Gynaecological Oncology, Medical University, 
      Bialystok, Poland.
FAU - Mueller, Arnd
AU  - Mueller A
AD  - Merckle GmbH, 89079, Ulm, Germany.
FAU - Bias, Peter
AU  - Bias P
AD  - Merckle GmbH, 89079, Ulm, Germany.
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
DEP - 20160610
PL  - England
TA  - Reprod Biol Endocrinol
JT  - Reproductive biology and endocrinology : RB&E
JID - 101153627
RN  - 0 (Follicle Stimulating Hormone, Human)
RN  - 0 (Recombinant Proteins)
RN  - 0 (follitropin alfa)
RN  - 9002-68-0 (Follicle Stimulating Hormone)
SB  - IM
MH  - Adult
MH  - Female
MH  - Follicle Stimulating Hormone/administration & dosage/adverse effects/*therapeutic 
      use
MH  - Follicle Stimulating Hormone, Human/administration & dosage/adverse 
      effects/*therapeutic use
MH  - Follow-Up Studies
MH  - Humans
MH  - Infertility, Female/*drug therapy
MH  - Ovarian Hyperstimulation Syndrome/chemically induced
MH  - Ovulation Induction/*methods
MH  - Patient Satisfaction
MH  - Pregnancy
MH  - Pregnancy Rate
MH  - Recombinant Proteins/administration & dosage/adverse effects/therapeutic use
PMC - PMC4902897
OTO - NOTNLM
OT  - Assisted reproductive technology (ART)
OT  - Follitropin alfa
OT  - Infertility
OT  - Ovaleap
OT  - r-hFSH
EDAT- 2016/06/12 06:00
MHDA- 2017/03/14 06:00
PMCR- 2016/06/10
CRDT- 2016/06/12 06:00
PHST- 2016/03/14 00:00 [received]
PHST- 2016/05/17 00:00 [accepted]
PHST- 2016/06/12 06:00 [entrez]
PHST- 2016/06/12 06:00 [pubmed]
PHST- 2017/03/14 06:00 [medline]
PHST- 2016/06/10 00:00 [pmc-release]
AID - 10.1186/s12958-016-0164-y [pii]
AID - 164 [pii]
AID - 10.1186/s12958-016-0164-y [doi]
PST - epublish
SO  - Reprod Biol Endocrinol. 2016 Jun 10;14(1):31. doi: 10.1186/s12958-016-0164-y.